AboutMesothelioma.Net

Extrapleural Pneumonectomy versus Pleurectomy/Decortication in the Surgical Management of Malignant Pleural Mesothelioma: Results in 663 patients

Tuesday, March 25, 2008

Source: The Journal of Thoracic and Cardiovascular Surgery

Extrapleural pneumonectomy (EPP) and pleurectomy/decortication (PD) are the two major surgical options for the treatment of pleural mesothelioma. An EPP is usually described as the complete resection of the pleura, the pericardium, the diaphragm and the entire lung on the affected side. With pleurectomy/decortication the lung is spared, but both the parietal and visceral pleurae are removed, as are the pericardium and the diaphragm if necessary. Both procedures are considered radical surgery, with EPP the more invasive of the two.

There is considerable controversy and debate in the mesothelioma community regarding which of the procedures is the most effective and what the conditions are that should govern the choice of the one over the other. Some previous studies have shown that patients who undergo PD are less likely to experience serious consequences and may have a longer post-surgery median survival, but the conclusions of these previous studies have often been questioned due to small sample size or an inability to directly compare the patient cohorts who completed the procedures.

In an attempt to settle this controversy, doctors from some of the country’s premier mesothelioma treatment centers have recently released the results of a study on the efficacy of EPP vs. PD in a large cohort of patients. The results of the individual treatments were analyzed on a number of different levels and the resulting analysis is the most complete yet offered about the relationship between EPP and PD and the conditions under which each procedure should be used.

Overview of the Study

The authors of the study undertook a retrospective analysis of 663 total patients who underwent an EPP (n=385) or a PD (n=278) between 1990 and 2006 at one of the following cancer centers: Memorial Sloan-Kettering Cancer Center, The National Cancer Institute or the Karmanos Cancer Institute. In looking at the historical records of these patients, their analysis compared not only the overall efficacy of the procedures themselves, but also the effect the various sub-groups had within the two major cohorts: histology, tumor staging, performance status, age, gender, etc., etc.

A number of important differences separate the present study from previous ones that also involved these procedures. In many of the prior studies, the surgical method was written-in to the study design itself and the actual procedure was only a part of the subsequent analysis. The procedures themselves were rarely compared directly and when they were other study factors would often limit the scope of the conclusions that could be drawn from the results. Another major difference between this study and previous ones was that the end points of earlier studies often looked only at time to progression, instead of overall survival, as the present study does. It is for these reasons, as well as others—such as the large sample size—that the authors describe this study as the largest, most comprehensive study yet completed on the use of extrapleural pneumonectomy versus pleurectomy/decortication.

As we said above, this study looked at 663 mesothelioma patients who underwent either EPP or PD during a sixteen-year period. Most patients were older males who presented with Stage II or Stage III disease characterized by the epitheloid histological subtype. However, there were important differences between the two groups. The patient cohort who underwent PD were on average older than the EPP group and more often presented with early stage disease, while the EPP group were more likely to receive some form of multimodal treatment and more often presented with epitheloid mesothelioma than did the PD group. The EPP group was also more likely to demonstrate more adverse post-surgical events than the PD was likely to.

When taken as an entire group, median survival was determined to be 14 months. However, this figure is truly an average and masks some very interesting findings. The over-all five year survival figure for the entire group was 12%. For patients who presented with Stage I disease, median survival rose dramatically to 38 months, while patients with stage II disease demonstrated a median survival of 19 months. Patients who were Stage III at time of presentation had a median survival of 11 months, while those with Stage IV disease averaged 7 months from diagnosis.

Other analyses that showed a significant impact on survivability were epithelial histological subtype, female gender and multi-modal therapy: all of which increased survival times.

A univariate analysis that compared PD to EPP showed that patients who underwent PD were associated with a significantly better median survival than did patients with EPP. However: this conclusion disappears when the analysis takes on a multi-variate methodology by considering the characteristics of the patient’s total presentation. When controlling for tumor stage, no significant differences were found between the PD group and the EPP group. The same is found when tumor stage is replaced by histology or gender. The differences that do exist between these cases are not significant enough to conclude that one procedure is somehow “better” or “more appropriate” than the other one is if presentation-specific elements are not accounted for. In fact, the authors specifically note the importance of taking the patient’s total presentation into account when deciding between the procedures.

In a discussion included at the end of article between the study’s lead author and peer reviewers of the study, Dr. Raja M. Flores, the lead author, and Dr. David Sugarbaker, Chief of the Division of Thoracic Surgery at Brigham and Women’s in Boston, discuss the importance of achieving macroscopic complete resection (MCR), i.e. removal of all visible tumor, to maximize the treatment’s efficacy. The choice of procedure will be made at the time of the thoracotomy, which is the procedure to open the chest cavity for surgery, and should be guided by the extent of tumor present. If the disease is caught in the early stages, P/D might suffice for MCR, but for advanced disease with significant spread and tumor bulk, an EPP is often the only procedure that could potentially achieve MCR, so that is the procedure that should be used.

Dr. Flores specifically states the two procedures are not interchangeable and they should not be seen that way.

Conclusion

The question of EPP vs. PD has long been a controversial debate among mesothelioma physicians. The authors of this study state that decisions on which procedure to use have more often been the result of surgeon bias rather than the application of sound science and one of their goals for the study was to help inform physicians on this question. In this, they have succeeded in providing valuable evidence regarding the efficacy and applicability of both extrapleural pneumonectomy and pleurectomy/decortication for the treatment of pleural mesothelioma. Neither procedure leads to statistically significant differences in overall survival, but each procedure is given a clear domain for use: PD for early stage disease and EPP for later stage disease or disease with a heavy tumor burden.

Even as they call for more studies comparing these two procedures, the authors have succeeded in making an important contribution to the controversy surrounding EPP vs. PD. However, neither procedure represents a truly curative approach to mesothelioma and the authors also call for more study and development of non-surgical treatments, as well as for more effective adjuvant therapy.

Labels: mesothelioma

posted by Belluck & Fox at 2:06 PM
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Anti-Cancer Drug CYT997 Update

Wednesday, March 19, 2008

Source: Cytopia Limited

Cytopia Limited, a privately-held biotechnology firm from Australia, has recently announced that its anti-cancer drug CYT997 has begun a Phase II clinical trial for the treatment of relapsed or refractory multiple myeloma. Cytopia also announced that along with an upcoming Phase II clinical trial for the treatment of glioblastoma multiforme, they are presently conducting a feasibility analysis for a Phase II study of the compound for mesothelioma patients who have failed Alimta therapy—the only FDA-approved therapy for the treatment of pleural mesothelioma.

CYT997 is part of a new class of anti-cancer drugs known as vascular disrupting agents (VDAs), which target and attempt to disrupt the relationship between tumors and blood vessels. CYT997 is a VDA that possesses multiple mechanisms of action. The first mechanism of action involves shutting down the blood vessels that deliver nutrients and oxygen to the tumor, while the second mechanism directs and engages in general cytotoxic activities.

The compound that CYT997 is based on was discovered by researchers from Cytopia in 2003 and in 2005 the FDA accepted Cytopia’s application to begin a Phase I trial. The success of Phase I trials has led Cytopia to begin the Phase II trials introduced in this article.

Labels: mesothelioma

posted by Belluck & Fox at 4:34 PM
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Tumour Growth Block Hopes Raised

Monday, March 17, 2008

Source: BBC News

Reseachers from the Harvard Medical School have recently identifed the enzyme, known as pyruvate kinase, that allows cancer cells to consume the large amounts of glucose that are necessary for their growth and continued propagation. Pyruvate kinase comes in two distinct forms, but only one of the forms—the PKM2 form—enables the consumption of glucose at the rate necessary to sustain tumor growth. When reserachers learned how to knock out PKM2 production and force the enzyme into its other form, they discovered they could stop the growth of the cancerous cells. When they tested this therapy in mice, they found that tumorgenesis was significantly inhibited.

Reserachers have known that tumors consume large amounts of glucose since the pioneering work of Otto Warburn, a Nobel Prize-winning chemist, discovered this over seventy years ago, but until this discovery they have not been able to develop therapies based on the knowledge. PET Scans, one of the major imaging modalities used in cancer diagnostics, are used to identify body-wide tumor growth by using radioactive tracers to examine areas of accelarated glucose consumption. PET has been a hugely successful diagnostic technology and is one of the prime examples of how science has previously incorporated the knowledge of glucose consumption into medicine.

With this discovery, doctors are now hopeful that new treatments can be developed that will literally starve the cancer of glucose and, therefore, stop tumor growth altogther. While the researchers note that all the forms of cancer they looked at during their review exhibitd this enzyme, whatever treatments are created with it will almost certainly have to take into consideration the particular metabolic activity of the individual cancers. More research is certainly needed to confirm these findings, but it appears that the discovery of pyruvate kinase represents a real advancement in our knowledge of the bio-chemical processes that underlie cancerous growth.

Labels: cancer, mesothelioma

posted by Belluck & Fox at 10:39 AM
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Mesothelin-related predictive and prognostic factors in malignant mesothelioma: A nested case-control study

Friday, March 14, 2008

Source: Lung Cancer
(Roe OD, et al., Mesothelin-related predictive and prognostic factors in malignant mesothelioma: A nested case-control study, Lung Cancer (2008), doi:10.1016/j.lungcan.2007.12.025)

The search to discover and develop effective markers for mesothelioma is one of the most active areas of mesothelioma research. Doctors and scientists are engaged in a number of programs whose ultimate goal is the creation of simple and reliable tests that can indicate a patient’s disease status at any point in time. There are three major avenues this research is being carried out on: the development of markers for mesothelioma diagnosis, which would allow definitive diagnoses earlier in the disease’s staging, using less-invasive techniques; the development of markers for prognosis tracking and disease progression, which would allow treating physicians to evaluate the efficacy of a patient’s treatment and to make adjustments to it by analyzing the relationship between therapy and marker levels; and, finally, the creation of markers for screening purposes, where likely candidates for mesothelioma development, such as people with a history of asbestos exposure and their families, could under-go a simple test to indicate any underlying change in status possibly indicative of cancer development—much in the same way that people over 50 are recommended colonoscopies for screening of possible colon cancer or the development of precancerous lesions.

In the search for these markers, a number of possible targets have been proposed, but one of the most often studied is mesothelin, a membrane-bound glycoprotein of the mesothelium that previous studies have shown is significantly over-expressed in people with malignant mesothelioma, especially pleural mesothelioma and peritoneal mesothelioma, as well as certain other cancers. Mesothelin is considered to play an important role in cell adhesion, as well as in inter-cell signaling and recognition. Another avenue of marker research in the mesothelin family involves soluble mesothelin-related protein (SMRP), which can be found in serum and in the fluid from pleural effusions, as opposed to mesothelin which is bound to the cell’s surface.

An international team of researchers, including scientists and doctors from Norway, Australia and France, have recently released the results of a study that analyzed the efficacy of these mesothelin-related markers for use in the screening of mesothelioma, as well as their use for mesothelioma diagnosis, prognosis development and progression testing.

Overview of the Study

Previous studies on mesothelin expression and SMRP levels have both shown high sensitivity and specificity regarding mesothelioma diagnosis. One of the studies noted by the present authors suggested that SMRP could also be a screening marker, as that study found elevated SMRP levels one–five years prior to a mesothelioma diagnosis in a subset of asbestos-exposed indviduals.

Along with SMRP, other serum markers that have been proposed as markers for mesothelioma include CYFRA 21-1 (Cytokeratin Fragment 19) and CA125 (Cancer Antigen 125)—both of which have shown elevated levels in previous studies of the disease. The authors specifically noted that some previous studies had implicated CA125 in peritoneal metastasis. They included these markers in their analysis as well, both to compare with SMRP expression and to analyze these levels on their own.

To make their analysis, the authors identified forty-seven archival cases of confirmed mesothelioma where tumor samples and pre-clinical serum were still available for each of the patients. 29 of these cases were identified as pleural mesothelioma, seven as peritoneal mesothelioma and there was a single diagnosis of mesothelioma of the tunica vaginalis, an exceedingly rare form of the disease. Histologically, the cases of pleural mesothelioma were split between 33 cases of epitheloid mesothelioma and 6 cases of bi-phasic mesothelioma. All of the peritoneal cases presented as epitheloid mesothelioma, while the tunica vaginalis case presented as bi-phasic mesothelioma. The levels of SMRP, CYFRA 21-1 and CA125 were then compared to a control group of 121 healthy adults. Mesothelin expression was examined only in the cases of confirmed mesothelioma.

The results of the pre-clinical serum marker tests showed no significant differences between the control group and the mesothelioma group in terms of mean marker levels, which led the authors to conclude that these markers should not be used as part of a screening process. They also noted that much more research needs to be completed in this area before a definitive conclusion can be delivered.

In 36 of the 47 mesothelioma cases (77%), mesothelin was expressed in more than 50% of the identified tumor cells. Three cases did not show any mesothelin expression, five showed expression in less than 25% of malignant cells and three showed expression between 26% and 50%. When mesothelin expression was identified in the bi-phasic cases, it was only in the epitheloid component, as the sarcomatous component in the mixed subtype always returned an expression value of zero. The authors did not find any correlation between mesothelin expression in tumors and SMRP levels in their pre-clinical serum samples.

The authors also divided the mesothelioma cases into two groups: those with mesothelin expression greater than 50% in tumor cells and those with less. Patients in the higher mesothelin expression group had a longer median survival figure at twelve months than did those in the less than 50% subgroup, which showed a median figure of only six months. When they compared mean survival between the pleural mesothelioma group and the peritoneal mesothelioma group, they found that the pleural group’s overall mean survival was eleven months, while the peritoneal group’s mean figure was forty-five months—a substantial difference indicative of the peritoneal disease’s typically enhanced prognosis. Further analysis showed that the peritoneal group highly expressed mesothelin in all its cases, while the pleural group did so in less (75%). Within the epithelial pleural subgroup, they correlated high mesothelin expression with a better prognosis as well.

These findings have led the authors to propose that mesothelin expression is not a marker of disease progression, but is in fact a marker of disease differentiation, so patients presenting with high mesothelin expression may reflect a disease subtype with a better prognosis due to less aggressive malignant behavior.

Conclusion

The authors conclude their paper stating that the serum markers they analyzed—SMRP, CA125 and CYFRA 21-1—were not recommended for use as screening markers. Further investigation into each marker, especially the relationship between mesothelioma, peritoneal metastasis/progression and CA125, is warranted by their expression by the disease, but their use as screening markers should be avoided. They also state that their hypotheses on mesothelin expression call for further research to confirm this behavior, as well as to explain its biological component.

Labels: mesothelioma

posted by Belluck & Fox at 2:31 PM
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A Conditional Mouse Model for Malignant Mesothelioma

Wednesday, March 12, 2008

Source: CancerCell.org

One of the most exciting areas of current mesothelioma research is the growing body of knowledge that has been discovered about the disease’s molecular and genetic foundations. Even though much of this research is still quite preliminary, doctors and scientists are successfully—albeit, slowly—adding to our understanding of the precise mutations responsible for the development of mesothelioma. A systematic understanding of the relationship between these various mutations has, however, not yet been developed. One of the important precursor steps in creating a cohesive model of human mesothelioma genesis is the development of a mouse model that properly accounts for the disease’s genesis and progression. Not withstanding the significant genetic and biological differences between mice and humans, the fact remains that many of the greatest successes in human medicine have been guided by results obtained from murine testing.

Researchers from the Netherlands have recently published an article that describes their development of a conditional mouse model for mesothelioma carcinogenicity. Their results were obtained through testing of mice bred with specific mutations. Through their analysis of the correlations between individual gene mutations and malignant behavior, they’ve drawn specific conclusions regarding the manner in which individual mutations are responsible for the development, behavior and progression of mesothelioma.

What follows is a summary of their findings.

Overview of the Study

As we have previously covered in these news updates, mesothelioma is one of the most difficult of all forms of cancer to treat effectively. In its most common form, pleural mesothelioma, it typically presents only in the disease’s later stages and almost universally with a poor prognosis. Peritoneal mesothelioma, the second most-common form of the disease, typically presents with a less aggressive behavior pattern and a longer-term median survival range, but neither form responds well to conventional cancer treatments. Because of this, the development of new treatment modalities takes on greater and greater importance. Gene therapy represents one of these promising new strategies, but the lack of specific models regarding the disease’s growth pattern has limited the creation of effective medicine with it. Now that the Dutch researchers have published their findings, many members of the mesothelioma research community will be looking at their results with great interest to see what they reveal about possible treatment targets.

Individual studies have separately reported on a number of genetic mutations that have been implicated in mesothelioma genesis. Mutations and subsequent dysfunction of the tumor suppressor genes INK4A and P14ARF have been previously been reported on, as have loss and mutation of NF2 and TRP53. The authors note that Ink4a/ARF and TRP53 play well-known roles in cell-cycle regulation, while reduced NF2 expression “lowers cell adhesion and induces Schwann cell proliferation, whereas enhanced expression of NF2 leads to growth arrest.” A number of other genes have also been proposed as conducive to mesothelioma development, but the genes mentioned above have received the most attention.

To develop their model, the researchers bred a number of mice families with mesothelial-specific mutations to the Nf2, p53 and Ink4a pathways so they could chart the effects that each of these mutations, both singularly and in combination with the other mutations, had on the development of mesothelioma in these mice. Their findings were indicative of the importance these genes play in mesothelioma carcinogenicity.

One of the first things the researchers studied was the role these mutations had on tumor growth in the first place. They reported that the mice developed a number of individual tumors, but mesothelioma was the single most common development. The most common origin sites for it were the visceral pleuras of the lung and heart, while the most common metastatic developments included the parietal pleura, the diaphragm and the thoracic chest well.

When they looked at the individual relationships between gene mutation and malignant events, they discovered that individual losses of NF2, p53 or Ink4 were all clearly indicative of mesothelioma genesis, but that the loss of all three often led to the development of the most aggressive behavior patterns in their sample. The average latency period (the time between the mice’s first exposure to asbestos and their development of mesothelioma) for mice presenting with NF2;p53 loss was 135 days and for mice with NF2;Ink4a/Arf loss it was 220 days, while the latency period in mice who exhibited loss of NF2;p53;Ink4A was only 80 days. All of the most aggressive epitheloid and sarcomatoid mesotheliomas,i.e., those that were invasive of both the visceral and the parietal pleura, were found in this same NF2;p53;Ink4A group, while mice in the NF2/p53 or NF2;Ink4a/Arf groups did not exhibit the same aggressive behavior. Because of this, the researchers conclude that the loss of Ink4a (especially Ink4a alone-not Ink4a/Arf) leads to the most aggressive malignancies.

The relationship of NF2 and p53 loss to mesothelioma development was also covered extensively in the paper, where the authors conclusively state the importance of these mutations to disease development and progression. The authors propose that exposure to asbestos directly leads to a number of damaging genetic events (“genotoxic effects”), such as loss of both NF2 and Ink4a/Arf, which they see as the origin of asbestos’ carcinogenicity. If their hypothesis is correct, this could be the beginnings of our understanding of the precise physical relationship between asbestos exposure and mesothelioma development.

With NF2 playing such an important role in the development of the disease, the authors wonder if therapies utilizing NF2 re-expression would be effective for the treatment of mesothelioma. They note that recent research on NF2 re-expression has demonstrated some experimental efficacy for inhibiting cell proliferation and impairing the spread and invasive potential of certain types of cells.

The authors discuss a number of other novel findings in the genesis of mesothelioma. We have only covered a small number of their findings in this summary, so we recommend interested readers to read the full article to learn more about this newly developed mouse model.

Conclusion

The development of this mouse model should spur further research into the genetic mutations that underlie mesothelioma development. A greater understanding of the interrelationship between these mutations is sure to shed significant light on the cellular behavior of the disease, which will—hopefully—lead to the development of more targeted and effective therapies.

Labels: mesothelioma

posted by Belluck & Fox at 9:19 AM
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Funding Sought for Iron Range Mesothelioma Research

Monday, March 10, 2008

Source: Duluth News Tribune

Minnesota’s Iron Range is an area where taconite and other forms of iron ore have been mined for generations. Epidemiological research over the previous few years has shown that miners in this area have developed mesothelioma at a much higher rate than the national average and many questions have been raised as to why this is. Taconite is a form of low-grade iron ore, but it is not an asbestos mineral, which is the only conclusively shown cause of pleural mesothelioma, as well as the other forms of the disease. A number of studies on standard taconite have confirmed that it does have an asbestos-like form, but that it is conclusively not an asbestos-mineral and, therefore, should not present with the same risks of exposure as does asbestos. However: the rate of mesothelioma in the Iron Range has generated new questions about taconite exposure and now the University of Minnesota is seeking funding for a number of studies on this question.

Officials from The University appeared before the Minnesota House to request $4.9 for the studies, which are expected to take of five years. $4.1 million will be devoted to the actual completion of the studies and $800,000 will be devoted to air quality testing in the area.

University health officials said that some of the questions the study seeks to answer will include: What was the actual cause of death of the approximately 70,000 miners employed in the state’s taconite mines between the 1950s to the 1980s. Is there a link between health conditions and the time spent in the miners? What—if anything—was the difference in harmful material exposures between the 58 miners who died of mesothelioma and those who didn’t develop the cancer?

All who are involved and aware of the situation support the commencement of the studies. The funding is sure to be received, but the manner in which it is approved will likely be the major negotiation. The findings are already early awaited by many people, but are most eagerly awaited by the miners and their families, as what can be understood about the exposures of the previous generations is likely to protect the lives and well-being of the younger miners who are just entering the industry today.

Labels: mesothelioma

posted by Belluck & Fox at 11:12 AM
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Asbestos Exposure during Routine Brake Lining Manufacture

Source: Industrial Health 2007, 45, 787-792

As awareness of the hazards of asbestos exposure became more common during the last few decades, many developed nations implemented statutory protocols strictly regulating the manner in which asbestos could be commercially used. Some of these nations even moved past regulation and enacted outright bans on the use of asbestos-family minerals. However, this pattern has not been duplicated among developing nations, where the use of asbestos has often continued unabated. Safety procedures that are necessary to protect the health of the work force have not been implemented in many of these nation’s factories and without active regulatory enforcement there is rarely any monitoring of air quality levels. The result is that workers continue to operate in unsafe environments where they are regularly exposed to extremely high levels of a known carcinogen, conclusively shown to cause all forms of mesothelioma, especially the two most common forms of the disease: pleural mesothelioma and peritoneal mesothelioma, as well as lung cancer and asbestosis.

In order to understand the exposure risks in these kinds of factories, Iranian researchers collected air samples from a brake lining manufacturing plant in Iran and compared their findings to the permissible exposure limit (PEL) regarding asbestos exposure developed and currently utilized by the Occupational Safety and Health Administration (OSHA).

Overview of the Study

The authors state that Iran has 26 brake lining manufacturing plans in current operation and the total workforce employed in those plants is approximately 3,000 people. They selected one of these plants to study overall air quality levels and to analyze the exposure risks of specific manufacturing processes. In selecting the lining manufacturing plant, the authors described some of the tasks performed, which included the grinding, beveling and drilling of materials, as well as a number of other procedures. Many of these tasks are dry processes, where the materials at hand release large amounts of dust into the air.

In measuring overall airborne dust samples, the authors found an average of particle concentration of 9.6 mg/m³, with the highest levels found in workers employed in the beveling process: 16.32 mg/m³. While the average figure is just below the threshold limit of 10 mg/m³ per day for total dust set by the American Conference of Governmental Industrial Hygienists, the bevellers, as well as those responsible for polish (11.40 mg/m³) and reassembly (11.54 mg/m³) found the particle density in their air exceeding ACGIH’s limits. OSHA’s threshold limit for this test is 15 mg/m³ , so the bevellers exceeded that limit as well.

To analyze the asbestos density in the plant’s breathable air, the authors used phase contrast optical microscopy (PCM), which is the standard technique for asbestos testing. The results returned showed an average fiber concentration of .78 f/cc, with the highest recorded level at 1.85 f/cc. With OSHA’s PEL (permissible exposure limit) for asbestos density set at only 0.1 fibers/cc, the average concentration level was 7.8 times greater than OSHA’s recommendation.

The authors completed their study in the summer, when ventilation was at its most effective, as the plant’s windows were all open because of the summer heat. The authors speculate that dust and asbestos levels during winter months would be much greater than the levels they measured because windows wouldn’t be open during winter, so ventilation would be less effective.

Conclusion

The results of the study clearly indicate asbestos and dust levels greater than OSHA recommendations. These levels also clearly indicate a heightened exposure risk for asbestos-related diseases, such as mesothelioma and lung cancer. In describing their paper as the first to look at asbestos levels in a brake lining manufacturing plant in Iran, the authors also see it as representative of asbestos levels found in plants in most developing countries. They strongly recommend improvements in ventilation and housekeeping to reduce contaminant levels.

Labels: asbestos

posted by Belluck & Fox at 9:54 AM
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Sensitive and Specific New Enzyme-Linked Immunosorbent Assay for N-ERC/Mesothelin

Thursday, March 6, 2008

Source: Clinical Cancer Research

Full Title: “Sensitive and Specific New Enzyme-Linked Immunosorbent Assay for N-ERC/Mesothelin Increases its Potential as a Useful Serum Tumor Marker for Mesothelioma”

The early diagnosis of mesothelioma is a crucial element in achieving the best prognosis. If the disease is discovered in its beginning stages it can be treated with aggressive tri-modal therapy, which may extend a person’s life significantly beyond the typical range of mesothelioma survivors. The problem, however, is that mesothelioma is difficult to diagnose in the early stages. It shares many common symptoms with less serious conditions and often goes undiagnosed until its more serious effects arise during the disease’s advanced stages. Diagnoses are also missed because the diffuse malignancy pattern typical of standard-form pleural mesothelioma means the cancer’s growth is often overlooked or not even rendered by imaging technologies during the disease’s earliest stages. What is needed—and is sorely lacking—is the development of a simple test that can easily return a diagnosis or at least an indication that mesothelioma may be at work.

A variety of research projects are actively working on just this issue, with the development of tumor makers specific to mesothelioma among the most important. A tumor marker is a diagnostic tool that can be used to easily test for the presence of a particular malignancy in the blood of patient or in a tissue sample not otherwise indicative of cancer. A number of markers have been proposed for mesothelioma diagnosis and researchers around the world are busy looking for the most effective ones. In 2006, a group of doctors and researchers from Japan proposed the use of N-ERC/mesothelin as another potential tumor marker for malignant pleural mesothelioma. These researchers have recently published an update to their original work that describes the development of an improved enzyme-linked immunosorbent assay (ELISA) system with a higher sensitivity and specificity for the detection of N-ERC/mesothelin in a blood sample.

Overview of the Study

To study the diagnostic value of N-ERC/mesothelin and the efficacy of their improved ELISA system, the authors enrolled 293 patients into their study. 39 patients presented with histologically-confirmed mesothelioma, 201 with an asbestos-related illness that was not mesothelioma, 45 with lung cancer and 8 with other malignancies. A group of 102 healthy people were used as a control group.

To establish baseline N-ERC/mesothelin levels, the authors first analyzed the group of healthy patients, who showed generally uniform levels without any statistically significant differences based on sex or smoking status, although there was some correlation between older patient age and increased N-ERC/mesothelin levels.

When the authors moved to the study of the mesothelioma group, they found significant correlation between this group and high N-ERC/mesothelin levels. Median levels for the mesothelioma cohort were significantly greater than the levels found in all other patient groups. They found that within this cohort, patients who presented with epitheloid mesothelioma demonstrated especially high levels. They also discovered a correlation between higher N-ERC/mesothelin levels and advanced stage disease. All of these results clearly point to the continued study of N-ERC/mesothelin as a tumor marker for mesothelioma.

Conclusion

It is hoped that the development of specific tumor markers will enable more diagnoses of early stage mesothelioma—a time when the disease appears much more responsive to therapy than it does in its later stages. The authors noted an article by David Sugarbaker that said patients who received aggressive tri-modal therapy during the early stages of the disease demonstrated a 5-year survival figure exceeding 40%. For a disease known mainly for its poor prognosis, a demonstration of 5-year survival figures is truly a cause for hope.

The authors conclude the paper stating that their use of N-ERC/mesothelin and the improved ELISA system has demonstrated clear diagnostic value and they call for more research into potential tumor markers. While confirmation of their findings must be made by independent researchers before we can definitively establish the efficacy of their system, everyone agrees that the development of a simple blood test for mesothelioma is one of the great goals of current mesothelioma research. Such a development would truly revolutionize the manner in which the disease would be treated, as patients could begin therapy much sooner than they currently do.

Labels: mesothelioma

posted by Belluck & Fox at 10:03 PM
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Localised Malignant Pleural Mesothelioma: A Separate Clinical Entity Requiring Aggressive Local Surgery

Wednesday, March 5, 2008

Source: European Journal of Cardio-Thoracic Surgery

Mesothelioma is an aggressive malignancy that primarily attacks the pleural surfaces surrounding the lungs, although it can also attack the peritoneum and—in rare cases—the pericardium and the mesothelial tissue surrounding the male reproductive system. Its normal behavior pattern is characterized by a diffuse spread of malignant cells throughout an entire surface area, where the boundaries between cancerous and non-cancerous tissues are blurred and often break down—making surgical resection of the cancer extremely difficult, if not impossible. This pattern is in marked contrast to other forms of cancer that present as locally-invasive, individually-identifiable tumors that evidence a clear boundary between the tumor and the otherwise healthy surrounding tissue.

Within the last decade, however, articles describing a number of cases that depart from this behavior pattern have appeared in the literature. These articles describe cases of histologically-proven pleural mesothelioma where individuals presented with locally-invasive pleural tumors that did not show any sign of diffuse spread and were more amenable to surgical resection than is the standard form of pleural mesothelioma. While these findings show a clear need for more research, its extreme rarity has limited researchers’ abilities to learn more about it. There are less than 100 proven cases of what is now known as localized malignant pleural mesothelioma in the literature, so large-scale studies of this subclass are currently impossible. Our knowledge of the disorder is anecdotal at best and is entirely based on journal descriptions of individual cases and presentations. Researchers from the United Kingdom have recently added to the literature on localized malignant pleural mesothelioma with an article that describes their experience with ten cases over an eight-year period.

What follows is a summary of their article.

Overview of the Study

The authors of the study work in the Department of Thoracic Surgery at Glenfield Hospital in Leicester, UK. During an eight-year period they performed surgery for 218 patients with pleural mesothelioma—10 of whom presented with the localized subtype under discussion here. These ten patients were all males and the median age at presentation was almost 66 years old. All had pathologically-confirmed malignant pleural mesothelioma. In terms of the histological subtypes of their diagnoses: four of the patients presented with epitheloid mesothelioma, four with sarcomatoid mesothelioma and two with the bi-phasic subtype. They all underwent surgery to remove a locally-invasive tumor that had infiltrated at least the chest wall: six presented with right-side infiltration and four with left-side infiltration. All patients underwent some form of pleurectomy: seven patients received a subtotal parietal pleurectomy, while the other three received a total parietal pleurectomy.

The results of the surgery were statistically much better than the results obtained after surgery for standard-form pleural mesothelioma. There were no deaths within 30 days of the surgery, although two needed drainage for post-surgery pleural effusions. The authors report microscopically complete resection in two patients and macroscopically complete resection in the remaining eight. Two patients died within one year of surgery (one at three months and one at ten months) and two more showed progression of the disease, but they were still alive during the period of the study. The authors report median survival at 56 months, which is much longer than the median survival range of 8–16 months typically reported for standard pleural mesothelioma. They also note that the longest survivor in their cohort was still alive at 70 months post surgery—a very rare occurrence for mesothelioma patients.

Conclusion

The authors concur with the previously published literature that localized malignant pleural mesothelioma has a distinctly different behavior pattern than does the standard-form disease. Using locally aggressive surgery, they were able to achieve some form of complete resection in all ten patients and their median survival figure of 56 months is quite a bit longer than anything reported in the literature on standard-form pleural mesothelioma. However, they are quick to note that a sample size of only ten cases isn’t nearly large enough to draw any definitive conclusions from and they call, as do most doctors who’ve had any experience with this rare malignancy, for more research into its biology and overall behavior.

Labels: mesothelioma

posted by Belluck & Fox at 10:18 PM
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Imaging of Pleural Masses: Which to Choose?

Tuesday, March 4, 2008

Source: Respirtory Medicine (2008) 102, 328-331

Imaging is one of the essential technology frameworks used in cancer diagnosis in general and for the diagnosis of mesothelioma in particular. Scientists have developed a number of different technologies that provide doctors with the tools to diagnose cancer, treat it and to track one’s progress in fighting it. While these tools are not perfect and have not cured cancer in toto, their successes cannot be discounted and it is not hyperbole to say that these imaging systems have truly revolutionized the practice of medicine in the United States and around the world. However, not all imaging technologies are created equal, nor can they be applied interchangeably. Each individual system has its own set of strengths and weaknesses and part of the job of doctors and researchers is to discover the strengths of the technology and maximize its use towards those ends, while also identifying its weaknesses and minimizing or stopping its use in scenarios that can exploit those weaknesses.

The imaging of pleural masses, such as those found in pleural mesothelioma, represents an especially important area of research as it requires as much precision as possible in the use of the available modalities. Because of the structure of the tissues involved, however, it can be difficult to return scans with high enough resolution to definitely determine a diagnosis. Because of this, doctors and researchers are actively studying which imaging modalities are the most effective for making certain kinds of diagnoses. It is within this light that doctors from the Ohio State University Medical Center in Columbus, Ohio have recently released a summation of their use of the standard imaging technologies in their diagnoses of pleural masses.

Introduction to the Study

The doctors compared the efficacy of the following imaging technologies for the diagnosis of pleural masses: chest radiography (chest x-ray), computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET). The doctors noted both the strengths and weaknesses of each system and made specific recommendations regarding the applicability of the technology for particular uses. While pleural mesothelioma remains the most feared of pleural malignancies, there are other malignancies which require imaging precision for the development of a definitive diagnosis as well.

Chest Radiography (X-Ray)

X-rays are the oldest and most commonly used imaging technology in medicine. An x-ray is frequently the first diagnostic test used by a doctor when pulmonary issues are suspected, but it’s rarely the final one in the diagnosis of pleural masses as its results are limited by poor resolution and it is not generally effective in the differentiation between benign and malignant tissue.

Computed Tomography (CT)

For the diagnosis of pleural issues, CT is a markedly superior technology to x-ray. Not only can CT better distinguish pleural disease from lung parenchymal (the functional tissues in the lungs, such as alevoli and alveolar duct) disease, but it is more adept at determining the location and extent of disease, detecting chest wall invasion and identifying pleural plaques.

Magnetic Resonance Imaging (MRI)

While CT has become the standard imaging technology for the diagnosis of pleural masses, MRI represents an improvement upon CT in a number of ways. It provides an image with superior soft tissue contrast, as well as superior spatial resolution, and this allows it to be even more sensitive to chest wall invasion or the invasion of adjacent tissues by cancerous cells than is CT. This latter facility is important in the staging of disease and in developing a resection strategy before surgery. However, MRIs cost has made it prohibitive for some of these purposes and its limited availability in certain areas has also restricted the number of people who can undergo it.

Positron Emission Tomography (PET)

PET is the newest of the modalities under discussion. While it has shown an ability to recognize individual tumors in the body and to show the results of distant metastases, its use for the diagnosis of pleural masses is limited because it’s not as effective as CT or MRI in showing chest wall or diaphragmatic infiltration.

Conclusion

The techniques discussed in this article all serve important medical functions and their applicability or inapplicability to the diagonosis of pleural masses should not be seen as invalidating their general use. As we said above, each of the technologies have their own strengths and weaknesses and the key is to maximize the use of these strengths and to minimize their use when their weaknesses impact their diagnostic value. CT remains the standard of care for most imaging involving pleural masses, but MRI does show improvements upon CT in a number of ways. With diseases such as pleural mesothelioma continuing to attack the lives of people, these technologies all serve important functions in the quest to keep patients healthy.

Labels: mesothelioma

posted by Belluck & Fox at 9:07 AM
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A Phase II Study of the Association of Glivec® Plus Gemzar® in Patients With Unresectable, Refractory, Malignant Mesothelioma

Saturday, March 1, 2008

Rationale

The purpose of this study is to evaluate the antitumor activity of a combination of Imatinib mesylate and Gemcitabine in patients with unresectable malignant mesothelioma expressing either PDGFR-beta or C-kit.

Date First Received: October 29, 2007
Last Updated: October 29, 2007
Verified by: Gruppo Italiano Mesotelioma, October 2007
Clinical Trial Phase: Phase 2 Start Date: January 2008
Overall Status: Not yet recruiting
Estimated Enrollment: 56

Brief Summary

Official Title: “A Phase II Study of the Association of Glivec® (Imatinib Mesylate, Formerly Known as STI 571) Plus Gemzar® (Gemcitabine) in Patients With Unresectable, Refractory, Malignant Mesothelioma Expressing Either PDGFR-Beta or C-Kit”

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study

Detailed Clinical Trial Description

PURPOSE Primary objective of the phase II ➢ Efficacy, i.e., response rate to study drugs

Secondary objectives of the phase II – Duration of response – Time to progression – Toxicity profile – Overall survival

PRIMARY VARIABLE The primary efficacy variable for the phase II part of the study is Best Overall Tumor Response, evaluated using the “Modified RECIST criteria for assessment of response in malignant pleural mesothelioma”

SECONDARY VARIABLES – Progression-free survival (PFS) form 1st administration onwards – Overall survival – Safety criteria, according to NCI-CTC criteria version 3.0

EFFICACY Objective tumor response assesed using the “Modified RECIST criteria for assessment of response in malignant pleural mesothelioma” SAFETY – Adverse events – Vital signs – Clinical and biohumoral findings

TREATMENT SCHEDULE – Gemzar 500 mg/m2, i.v., days 1 and 8 of a 21-days schedule, plus – Glivec 400 mg/die., per os

STATISTICAL DESIGN The study follows a two-stage design, according to the Simon model. We assume that with a response rate of 5% (H0) or less the drug is likely to be ineffective, and also, that, for the drug to be effective, a target response rate of 15% (H1) is required.

With a probability errors alfa of 5% and beta 20%, the calculated sample size is as reported in “PLANNED NUMBER OF PTS.”

PLANNED NUMBER OF PTS. 23 or 56 patients, evaluable for efficacy. The number depends on the response rate. When 2 or more objective responses, i.e., CR or PR, are observed in the first 23 patients, the total number of patients will be increased to 56, otherwise the study will be stopped

STATISTICAL EVALUATION Efficacy and safety variables will be evaluated descriptively. Indeed, ORR estimates and its exact 95% confidence interval will be calculated. Kaplan-Meier method will be used to estimate duration of response, PFS and OS

DURATION OF TREATMENT All patients are scheduled to receive at least two cycles of chemotherapy unless there is unacceptable toxicity, progressive disease, or the patient requires or asks for withdrawal from the study Responding patients will receive treatment for 6 cycles or earlier if progression or unbearable toxicity Disease status will be re-evaluated every two cycles, using the same imaging procedures used at baseline, i.e., CT or NMR

INCLUSION CRITERIA – Age of > 18 years and

EXCLUSION CRITERIA – Co-existing tumors of different histologic origin, except non melanomatous localized skin cancer and/or in situ cervical carcinoma

- A history of earlier tumors of different histologic origin being in complete remission since less than 5 years

- Unresolved toxicity from prior antitumor treatment(s)

- Primary peritoneal mesothelioma

- Any of the following abnormal baseline hematological values:

- Hb 2.5 mg/dL – ALAT and ASAT > 3 x UNL (unless due to liver metastases)

- Serum creatinine > 1.5 mg/dL

- Clinically relevant cardiovascular disease, i.e., myocardial infarction or other severe coronary artery diseases within the prior 6 months, cardiac arrythmia requiring medication, uncontrolled hypertension, overt cardiac failure or non compensated chronic heart disease in NYHA class II or more

- History of psychiatric disabilities, potentially interfering with the capability of giving adequate informed consent

- Pregnant or lactating women or inability/unwillingness to practice a medically approved method of contraception during study period (including 3 months following the end of treatment)

- Uncontrolled active infections

- Any condition which, in the judgement of the Investigator, would place the patient at undue risk or interfere with the results of the study

Outcome Measures for this Clinical Trial

Primary: Overall response rate Every two months

Secondary: Progression-free-survival; Overall Survival; Safety Follow-up after end of treatment will be every three months; safety will be analyzed throughout the whole study

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Gruppo Italiano MEsotelioma

Medical Oncology, IRCCS San Matteo University Hospital Foundation

Pavia 27100 Italy

Overall Clinical Trial Officials and Contacts

Camillo Porta, MD Principal Investigator Medical Oncology, IRCCS San Matteo University Hospital Foundation, pavia, Italy

Overall Contact: Camillo Porta, MD +39-0382-501355 c.porta@smatteo.pv.it

Additional Information

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00551252

Study ID Number: GIMe/01/06

ClinicalTrials.gov Identifier: NCT00551252

Labels: ClinicalTrial

posted by Your Attorney at 4:23 PM
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Extrapleural Pneumonectomy, IHOC Cisplatin and Gemcitabine With Amifostine and Sodium Thiosulfate Cytoprotection for Resectable Malignant Pleural Meso

Rationale

After removal of visible cancer in the chest, chemotherapy drugs are used to kill or stop tumor cells from dividing, so that they stop growing or/and die. Cisplatin is currently used safely as in intra-operative treatment for malignant pleural mesothelioma. This study is aimed to determine if the addition of gemcitabine as a second intracavitary chemotherapy can be accomplished safely…

Date First Received: December 10, 2007
Last Updated: December 20, 2007
Verified by: Dana-Farber Cancer Institute, December 2007
Clinical Trial Phase: Phase 1 Start Date: November 2007
Overall Status: Recruiting
Estimated Enrollment: 36

Brief Summary

Official Title: Phase I Trial of Extrapleural Pneumonectomy, Intrathoracic/Intraperitoneal Hyperthermic (IOHC) Cisplatin and Gemcitabine With Intravenous Amifostine and Sodium Thiosulfate Cytoprotection for Patients With Resectable Malignant Pleural Mesothelioma.

Condition Keyword(s): Malignant Pleural Mesothelioma

Procedure: Extrapleural pneumonectomy (EPP)

Drug: cisplatin
Drug: gemcitabine
Drug: amifostine
Drug: sodium thiosulfate

Purpose

This is a Phase I trial to study the efficacy of combination chemotherapy consisting of gemcitabine and cisplatin administered in the operating room and put into the chest and abdomen for one hour. We are also looking at the effects of heating the chemotherapy to a temperature of 42 degrees Celsius and the effect of cytoprotection agents: amifostine and sodium thiosulfate to counteract potential side effects of chemotherapy.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety Study

Detailed Clinical Trial Description

• This is a dose escalation study of gemcitabine with a fixed dose of cisplatin

• Patients will undergo surgery with Extrapleural Pneumonectomy, which entails the removal of the inner and outer lining of the lung (pleura) and the lung itself, including the lining overlying the pericardium and diaphragm. Resection of the pericardium and diaphragm are occasionally necessary to remove all visable tumor. This surgery is part of standard care for malignant pleural mesothelioma.
• After surgery, a one hour lavage with heated cisplatin and or gemcitabine will be administered to the hemithorax (and abdominal regions if the diaphragm is no longer present).
• Patients will remain hospitalized until they have recovered from surgery (usually 7-14 days).
• Patients will return to the hospital during the first month after their surgery to be evaluated by the medical staff.
• Dose escalation: 1) Three patients will be treated at the first dose level of gemcitabine. Labs will be monitored on a weekly basis, including a CBC, Chem-7, and LFT’s. In the absence of developing dose-limiting toxicity (DLT) among the first 3 patients treated, dosages can be escalated. DLT will be defined as any grade 3 or higher renal toxicity, thrombocytopenia or other grade 3 toxicity not related to surgery

  2) If none of these 3 patients have any toxicity, we will proceed to the next level of gemcitabine.

  3) If DLT occurs in 1 of 3 patients at a given dose level, then 3 additional patients are added at that dose (for a total of 6 at this level)If no DLT occurs, we will proceed to the next level of gemcitabine. If DLT occurs in another patient, this dose is considered the maximum tolerated dose (MTD).

  4) At any dose, 3 cases of DLT lead to discontinuation of recruitment at that dose and enrollment of 3 additional patients at a lower dose.

Outcome Measures for this Clinical Trial

Primary: To establish the maximally tolerated dose (MTD) of intraoperative Intrathoracic/Intraperitoneal hyperthermic gemcitabine and cisplatin combination modulated by amifostine and sodium thiosulfate in patients with malignant pleural mesothelioma. 2 years

Secondary: To determine and quantitate the safety of this combination in these patients by defining the dose limiting toxicity. 2 years

To study the pharmacokinetics of gemcitabine and cisplatin combination administered in this way. 2 years

Inclusion Criteria

Histologically-proven diagnosis of stages I to III malignant mesothelioma of the pleura and negative mediastinal N2 lymph nodes (Malignancy is confined to the affected hemithorax)

Adequate organ function including the following: adequate cardiac function, pulmonary function, renal and hepatic function and bone marrow reserve

Adequate overall physical activity

Surgical candidate for Extrapleural Pneumonectomy (EPP)

Exclusion Criteria

Extended disease outside the ipsilateral hemithorax as proven histologically, radiologically and/or intraoperatively

Have received chemotherapy and or radiation therapy within the last 3 years at the time of study entry

Serious concomitant systemic disorders

Second active primary malignancy (to exclude non- melanoma skin cancer)

Pregnancy at the time of the operation

Psychiatric or addictive disorder which would preclude obtaining informed consent

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Brigham and Women’s Hospital
Brigham and Women’s Hospital
Boston Massachusetts 02115 United States
Overall Clinical Trial Officials and Contacts
David J Sugarbaker, MD Principal Investigator Brigham and Women’s Hospital

Overall Contact: David Sugarbaker, M.D. 617-732-5004 dsugarbaker@partners.org

Additional Information

Link to the current ClinicalTrials.gov record: http://clinicaltrials.gov/show/NCT00571298

Study ID Number: 07-091

ClinicalTrials.gov Identifier: NCT00571298

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

posted by Your Attorney at 4:22 PM
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Phase II Study of Bevacizumab, Pemetrexed and Carboplatin as First-Line Therapy in Malignant Pleural Mesothelioma

Date First Received: December 4, 2006

Last Updated: August 28, 2007

Rationale

Official Title: “Phase II Study of the Combination of Bevacizumab Plus Pemetrexed and Carboplatin as First-Line Therapy in Patients With Malignant Pleural Mesothelioma”

Condition Keyword(s): Mesothelioma

Intervention(s):

Drug: bevacizumab
Drug: pemetrexed
Drug: carboplatin

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Detailed Clinical Trial Description

The primary objective is to assess antitumor activity of the combination of bevacizumab, pemetrexed and carboplatin, in terms of time to progression.

Secondary endpoints are to evaluate: – the objective response rate (RR) of the combination; – the toxicity and the safety profile of the combination; – the duration of response (RD) and time to treatment failure (TTF); – the overall survival (OS)

Outcome Measures for this Clinical Trial

Primary
Time to progression (TTP) from first day of treatment until first observation of disease progression or death due to any cause or the last date the patient was known to be progression free or alive.

Secondary
Response rate (RR) assessed according to modified RECIST criteria for Malignant Pleural Mesothelioma.

Overall survival (OS) computed as the time between the first day of treatment and the date of death or the last date the patient was known to be alive.

Inclusion Criteria

• Histologically proven malignant pleural mesothelioma, inoperable, non previously treated with chemotherapy including intracavitary administration;
  PS 0-1;
• measurable and/or evaluable lesions according to RECIST criteria;
• adequate organ function.

Exclusion Criteria

- uncontrolled hypertension;
- evidence of bleeding diathesis or coagulopathy;
- pregnancy or breast-feeding.

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Istituto Clinico Humanitas

Istituto Clinico Humanitas

Rozzano Milan 20089 Italy

Overall Clinical Trial Officials and Contacts

Armando Santoro, MD Principal Investigator Istituto Clinico Humanitas

Overall Contact: Armando Santoro, MD +39 02 8224 armando.santoro@humanitas.it

References

Ceresoli GL, Zucali PA, Favaretto AG, Grossi F, Bidoli P, Del Conte G, Ceribelli A, Bearz A, Morenghi E, Cavina R, Marangolo M, Parra HJ, Santoro A. Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma. J Clin Oncol. 2006 Mar 20;24(9):1443-8.

Ceresoli GL, Chiti A, Zucali PA, Rodari M, Lutman RF, Salamina S, Incarbone M, Alloisio M, Santoro A. Early response evaluation in malignant pleural mesothelioma by positron emission tomography with [18F]fluorodeoxyglucose. J Clin Oncol. 2006 Oct 1;24(28):4587-93.

Additional Information

Information obtained from ClinicalTrials.gov on April 15, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00407459

Study ID Number: ONC-2006-003

ClinicalTrials.gov Identifier: NCT00407459

Labels: ClinicalTrial

posted by Your Attorney at 4:09 PM
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A Study of VEGF-Antisense Oligonucleotide in Combination With Pemetrexed and Cisplatin for the Treatment of Advanced Malignant Mesothelioma

Date First Received: April 25, 2008

Last Updated: April 28, 2008

Clinical Trial Phase: Phase 1/Phase 2 | Start Date: April 2008

Overall Status: Not yet recruiting

Estimated Enrollment: 71

Rationale

Official Title: “A Phase I/II Study of VEGF-Antisense Oligonucleotide (VEGF-AS, Veglin) in Combination With Pemetrexed and Cisplatin for the Treatment of Advanced Malignant Mesothelioma”

Condition Keyword(s): Mesothelioma

Drug: VEGF-Antisense Oligonucleotide , Pemetrexed, Cisplatin

This will be a single institution non-randomized phase I/II trial for patients with malignant mesothelioma stage II and above, who have not received prior chemotherapy for their disease.

The purpose of this phase is to select a dose of VEGF-AS (antiangiogenesis drug)to be given with standard doses of pemetrexed followed by cisplatin on day 1 of a 21-day cycle.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study

Detailed Clinical Trial Description

The Study Objectives in Phase I are: To determine the safety of the combination of VEGF-Antisense Oligonucleotide (VEGF-AS, Veglin™) plus Pemetrexed and Cisplatin in subjects with advanced Malignant Mesothelioma,.via a dose escalation protocol. To determine the Maximum Tolerated Dose (MTD) and Dose Limiting Toxicity (DLT) of VEGF-AS plus Premetrexed and Cisplatin. To determine the time to disease progression To determine the objective response rate of the combination of VEGF-AS plus Pemetrexed and Cisplatin for the treatment of advanced malignant mesothelioma

The study Objectives in Phase II are: To further characterize the toxicity experienced by patients with malignant mesothelioma treated with VEGF-AS plus Cisplatin and Pemetrexed.
To determine median and overall survival.

The Laboratory objectives are: To measure plasma VEGF levels before, during, and after therapy as a correlate of outcome. To determine the pharmacokinetic profile of VEGF-AS plus Pemetrexed and Cisplatin.

Outcome Measures for this Clinical Trial

Primary:
• The primary endpoint of the phase II trial will be time to progression Tumor measurements every 6 weeks

Secondary:
• Secondary endpoints are objective response rate and overall survival Every 6 weeks evaluations

Inclusion Criteria

• Patients must have histologically or cytologically confirmed malignant pleural mesothelioma, epithelial, sarcomatoid, or mixed subtype
• Patients must have measurable disease,using RECIST criteria.Pleural effusions and ascites are not considered measurable lesions.
• Patients with pleural mesothelioma must be IMIG stage ≥II
• Age greater than or equal to 18 years.
• ECOG performance status less than or equal to 2 and an estimated survival of at least 3 months
• Patients must have adequate organ and marrow function: Absolute neutrophil count greater than or equal to1,500 Platelets greater than or equal to 100,000 Total bilirubin less than or equal to2.0x the upper limits of institutional normal
• AST/ALT less than or equal to 2.0x the upper limits of institutional normal Creatinine
• Clearance greater than 50ml/min
• The effects of VEGF-AS on the developing human fetus are unknown.
• Pemetrexed may cause fetal harm when administered to a pregnant woman and is classified pregnancy category D. There are no studies of pemetrexed in pregnant women. Cisplatin is also categorized as FDA Pregnancy Category D. There is positive evidence of human fetal risk. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent.
• Patients with history of prior cured malignancy > 5 years since the completion of treatment may be accrued provided that other eligibility criteria are met.

Exclusion Criteria

• Patients who have had chemotherapy for Mesothelioma prior to study entry
• Patients who have had radiation therapy within 3 weeks prior to entering the study.
• All patients should have recovered from all toxicities of prior therapy.
• Patients receiving therapy with other investigational agents at the time of study enrollment.
• Patients with uncontrolled brain metastases
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant and nursing women are excluded from this study
• Patients who had any major surgery within 4 weeks

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Norris Comprehensive Cancer Center
USC/Norris Comprehensive Cancer Center
Los Angeles California 90033 United States

Overall Clinical Trial Officials and Contacts
Barbara Gitlitz, MD Principal Investigator University of Southern California
Overall Contact: Gina Tse, RN 323/865-0514 Tse_G@ccnt.usc.edu

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00668499
Study ID Number: 18M-07-2
ClinicalTrials.gov Identifier: NCT00668499

Labels: ClinicalTrial

posted by Your Attorney at 3:48 PM
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Mesothelioma Avastin Plus Pemetrexed-Cisplatin Study

Clinical Trial Phase: Phase 2/Phase 3 Start Date: February 2008
Overall Status: Recruiting
Estimated Enrollment: 445

Rationale

Official Title: “A Phase II-III Randomized Trial Pemetrexed-Cisplatin Chemotherapy With or Without Bevacizumab (Avastin), 15 mg/kg, for Malignant Pleural Mesothelioma (MPM)”

Condition Keyword(s): Mesothelioma

Drug: Standard Chemotherapy (Pemetrexed and Cisplatin)
Drug: Standard Chemotherapy (Pemetrexed and Cisplatin) + Bevacizumab

Our hypothesis is that the addition of bevacizumab to the standard chemotherapy treatment of MPM will improve overall survival and quality of life beyond that achieved with chemotherapy alone.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Detailed Clinical Trial Description

A phase II trial associating the reference chemotherapy (pemetrexed plus cisplatin) with bevacizumab is needed to ensure that no specific toxicity is induced by this association, and that this triplet have interesting activity. As pleural mesothélioma is a rare tumor, a phase III trial, using the survival data from the phase II part study, will be able to include a sufficient number of patients, in a reasonable period of time, to answer the question of efficacy of the anti-angiogenic triplet, providing the efficacy outcomes could be considered as favorable, at the end of the phase II part of the study.

Outcome Measures for this Clinical Trial

Primary: % of patients with controled disease (responder and stable patients) at 6 months 3-month

Secondary: Overall Survival month

Inclusion Criteria

• Malignant, histologically proved, non resectable pleural Mesothelioma
• In case of pleural effusion, a talc pleurodesis, although not recommended, is allowed in accordance with current local practice, at the time of diagnostic thorascopy, with inclusion CT scan performed after pleurodesis.
• ECOG Performance status 0-2
• Mesothelioma with only pleural effusion without uni- or bidimensionally measurable disease will be eligible (adapted RECIST criteria)
• At least 18 years of age, less than 76 years of age
• Radiation therapy of thoracocentis tract (3 x 7Gy) performed before beginning medical study treatment, and the interval between thoracoscopic procedure and radiation will not exceed 28 days

Exclusion Criteria

• Prior chemotherapy
• Brain metastasis
• History of cerebral vascular accident (CVA) or transient ischemic attack

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Intergroupe Francophone de Cancerologie Thoracique
Institut Jules Bordet
BRUXELLES 1000 Belgium
APHP – Hopital Tenon – Pneumologie
PARIS 75020 France

Overall Clinical Trial Officials and Contacts
Gilles Robinet, Dr Study Director GFPC

Overall Contact: Gérard Zalcman, Pr 33-2-31-06-44-76

References

Porret E, Madelaine J, Galateau-Sallé F, Bergot E, Zalcman G. [Epidemiology, molecular biology, diagnostic and therapeutic strategy of malignant pleural mesothelioma in 2007 - an update] Rev Mal Respir. 2007 Oct;24(8 Pt 2):6S157-64. French.

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00651456
Study ID Number: IFCT-GFPC-ELCWP-0701
ClinicalTrials.gov Identifier: NCT00651456

Labels: ClinicalTrial

posted by Your Attorney at 3:46 PM
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Extrapleural Pneumonectomy, IHOC Cisplatin and Gemcitabine With Amifostine and Sodium Thiosulfate Cytoprotection for Resectable MPM

Clinical Trial Phase: Phase 1 Start Date: November 2007
Overall Status: Recruiting
Estimated Enrollment: 36

Condition Keyword(s): Malignant Pleural Mesothelioma

Procedure: Extrapleural pneumonectomy (EPP)

Drug: cisplatin
Drug: gemcitabine
Drug: amifostine
Drug: sodium thiosulfate

Rationale

After removal of visible cancer in the chest, chemotherapy drugs are used to kill or stop tumor cells from dividing, so that they stop growing or/and die. Cisplatin is currently used safely as in intra-operative treatment for malignant pleural mesothelioma.

This study is aimed to determine if the addition of gemcitabine as a second intracavitary chemotherapy can be accomplished safely.

This is a Phase I trial to study the efficacy of combination chemotherapy consisting of gemcitabine and cisplatin administered in the operating room and put into the chest and abdomen for one hour. We are also looking at the effects of heating the chemotherapy to a temperature of 42 degrees Celsius and the effect of cytoprotection agents: amifostine and sodium thiosulfate to counteract potential side effects of chemotherapy.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety Study

Detailed Clinical Trial Description

• This is a dose escalation study of gemcitabine with a fixed dose of cisplatin
• Patients will undergo surgery with Extrapleural Pneumonectomy, which entails the removal of the inner and outer lining of the lung (pleura) and the lung itself, including the lining overlying the pericardium and diaphragm. Resection of the pericardium and diaphragm are occasionally necessary to remove all visable tumor. This surgery is part of standard care for malignant pleural mesothelioma.
• After surgery, a one hour lavage with heated cisplatin and or gemcitabine will be administered to the hemithorax (and abdominal regions if the diaphragm is no longer present).
• Patients will remain hospitalized until they have recovered from surgery (usually 7-14 days).
• Patients will return to the hospital during the first month after their surgery to be evaluated by the medical staff.
• Dose escalation: 1) Three patients will be treated at the first dose level of gemcitabine. Labs will be monitored on a weekly basis, including a CBC, Chem-7, and LFT’s. In the absence of developing dose-limiting toxicity (DLT) among the first 3 patients treated, dosages can be escalated. DLT will be defined as any grade 3 or higher renal toxicity, thrombocytopenia or other grade 3 toxicity not related to surgery 2) If none of these 3 patients have any toxicity, we will proceed to the next level of gemcitabine. 3) If DLT occurs in 1 of 3 patients at a given dose level, then 3 additional patients are added at that dose (for a total of 6 at this level)If no DLT occurs, we will proceed to the next level of gemcitabine. If DLT occurs in another patient, this dose is considered the maximum tolerated dose (MTD). 4) At any dose, 3 cases of DLT lead to discontinuation of recruitment at that dose and enrollment of 3 additional patients at a lower dose.

Outcome Measures for this Clinical Trial

Primary: To establish the maximally tolerated dose (MTD) of intraoperative Intrathoracic/Intraperitoneal hyperthermic gemcitabine and cisplatin combination modulated by amifostine and sodium thiosulfate in patients with malignant pleural mesothelioma. 2 years

Secondary: To determine and quantitate the safety of this combination in these patients by defining the dose limiting toxicity. 2 years; To study the pharmacokinetics of gemcitabine and cisplatin combination administered in this way. 2 years

Inclusion Criteria

• Histologically-proven diagnosis of stages I to III malignant mesothelioma of the pleura and negative mediastinal N2 lymph nodes (Malignancy is confined to the affected hemithorax)
• Adequate organ function including the following: adequate cardiac function, pulmonary function, renal and hepatic function and bone marrow reserve
• Adequate overall physical activity
• Surgical candidate for Extrapleural Pneumonectomy (EPP)

Exclusion Criteria

• Extended disease outside the ipsilateral hemithorax as proven histologically, radiologically and/or intraoperatively
• Have received chemotherapy and or radiation therapy within the last 3 years at the time of study entry
• Serious concomitant systemic disorders
• Second active primary malignancy (to exclude non- melanoma skin cancer)
• Pregnancy at the time of the operation
• Psychiatric or addictive disorder which would preclude obtaining informed consent

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Brigham and Women’s Hospital
Brigham and Women’s Hospital
Boston Massachusetts 02115 United States

Overall Clinical Trial Officials and Contacts
David J Sugarbaker, MD Principal Investigator Brigham and Women’s Hospital
Overall Contact: David Sugarbaker, M.D. 617-732-5004 dsugarbaker@partners.org

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00571298
Study ID Number: 07-091
ClinicalTrials.gov Identifier: NCT00571298

Labels: ClinicalTrial

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Vaccine Therapy and GM-CSF in Treating Patients With Acute Myeloid Leukemia, Myelodysplastic Syndromes, Non-Small Cell Lung Cancer, or Mesothelioma

Clinical Trial Phase: Phase 1 | Start Date: October 2006
Overall Status: Recruiting
Estimated Enrollment: 20

Rationale

Vaccines made from peptides may help the body build an effective immune response to kill cancer cells. Biological therapies, such as GM-CSF, may stimulate the immune system in different ways and stop cancer cells from growing. Giving vaccine therapy together with GM-CSF may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects of vaccine therapy and GM-CSF in treating patients with acute myeloid leukemia, myelodysplastic syndromes, non-small cell lung cancer, or mesothelioma.
Study Type: Interventional
Study Design: Treatment
Detailed Clinical Trial Description

OBJECTIVES: Primary – Determine the safety and immunogenicity of the Wilms tumor-1 analog peptide vaccine in patients with acute myeloid leukemia, myelodysplastic syndromes, non-small cell lung cancer, or mesothelioma.
Secondary – Determine the antitumor effects of this vaccine in these patients.

OUTLINE: This is a pilot study. Patients are stratified according to disease type (acute myeloid leukemia [AML] or myelodysplastic syndromes [MDS] vs non-small cell lung cancer or mesothelioma).
Patients receive vaccine comprising Wilms-tumor 1 (WT-1) analog peptide emulsified in Montanide ISA-51 subcutaneously (SC) once in weeks 0, 4, 6, 8, 10, and 12 and sargramostim (GM-CSF) SC twice in weeks 0, 4, 6, 8, 10, and 12 (on the day of and 2 days prior to each vaccination). Patients who have an immunologic response and have no disease progression may receive up to 6 more vaccinations approximately 1 month apart.
Blood samples are collected at baseline, week 8, and week 14. Samples are examined by polymerase chain reaction (PCR) to measure levels of WT-1 and by T-cell proliferative response, delayed-type hypersensitivity against WT-1 peptides, or ELISPOT to measure immune response.
Bone marrow samples are collected from patients with AML or MDS at baseline and week 14.

Samples are examined by PCR to measure levels of WT-1 and by multiparameter flow cytometry to measure residual disease.

Intervention(s)

• Drug: WT-1 analog peptide vaccine
• Drug: incomplete Freund’s adjuvant
• Drug: sargramostim
• Procedure: diagnostic procedure
• Procedure: flow cytometry
• Procedure: immunoenzyme technique
• Procedure: non-specific immune-modulator therapy
• Procedure: non-tumor cell-derivative vaccine therapy
• Procedure: polymerase chain reaction

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Outcome Measures for this Clinical Trial

Primary

• Safety and immunogenicity
• Immune response as measured by T-cell proliferative response, delayed-type hypersensitivity against WT-1 peptides, or ELISPOT

Secondary

• Antileukemic effects
• Clinical and molecular response
• Antitumor response as measured by CT scan based on RECIST criteria
• Toxicity as measured by NCI CTC v. 3.0

DISEASE CHARACTERISTICS

• Cytologically or histologically confirmed diagnosis of 1 of the following:
• Acute myeloid leukemia, meeting the following criteria:
• Documented Wilms tumor-1 (WT-1)-positive disease demonstrated by WT-1 protein on a pretreatment bone marrow biopsy OR detectable disease with real-time quantitative reverse transcriptase-polymerase chain reaction (RQ-PCR)
• Completed induction chemotherapy, achieved clinical remission, and completed postremission therapy OR achieved clinical remission and have no plans for further postremission chemotherapy (≥ 65 years of age)
• Myelodysplastic syndromes, meeting the following criteria:
  • Documented WT-1-positive disease demonstrated by WT-1 protein on a pretreatment bone marrow biopsy OR detectable disease by RQ-PCR
  • International Prognostic Scoring System (IPSS) score of ≥ Int-2
  • Not a candidate for cytotoxic chemotherapy
• Non-small cell lung cancer, meeting the following criteria:
  • Positive tumor staining for WT-1 in > 10% of cells
  • Stage III or IV disease
  • Completed chemotherapy, surgery, and/or radiotherapy
• Mesothelioma, meeting the following criteria:
  • Positive tumor staining for WT-1 in > 10% of cells
  • Unresectable or relapsed disease
  • Chemo-naive or received 1 prior chemotherapy regimen
  • Malignant pleural mesothelioma or peritoneal mesothelioma
  • No leptomeningeal disease
  • No CNS involvement

PATIENT CHARACTERISTICS

• Karnofsky performance status 70-100%
• Absolute neutrophil count ≥ 1,000/mm³
• Platelet count > 50,000/mm³ (except for myelodysplastic syndromes where parameter is >
• 20,000/mm³ and not transfusion dependent)
• Bilirubin ≤ 2.0 mg/dL
• AST and ALT ≤ 2.5 times upper limit of normal
• Creatinine ≤ 2.0 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infection requiring systemic antibiotics, antiviral, or antifungal treatments
• No serious unstable medical illness

PRIOR CONCURRENT THERAPY

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy or radiotherapy
• No concurrent systemic corticosteroids

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Memorial Sloan-Kettering Cancer Center
Memorial Sloan – Kettering Cancer Center
New York New York 10021 United States

Overall Clinical Trial Officials and Contacts
Lee M. Krug, MD Principal Investigator Memorial Sloan-Kettering Cancer Center

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00398138
Study ID Number: CDR0000513334
ClinicalTrials.gov Identifier: NCT00398138

Labels: ClinicalTrial

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Pemetrexed Plus Cisplatin Neoadjuvant Therapy Followed By Surgery and Radiation in Mesothelioma

Clinical Trial Phase: Phase 2 Start Date: June 2005
Overall Status: Recruiting
Estimated Enrollment: 53

Rationale

Condition Keyword(s): Mesothelioma

Interventions:
Drug: pemetrexed
Drug: cisplatin

Phase II trial of Neoadjuvant Chemotherapy with Pemetrexed plus Cisplatin followed by Surgery and Radiotherapy in patients with Malignant Pleural Mesothelioma stage I-III.

The event-free survival is the primary endpoint for this study. This is a multicenter study and 53 Patients will be enrolled by June 2008.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Outcome Measures for this Clinical Trial

Primary: Event-free survival baseline to objective progression, start of new therapy or death from any cause

Secondary

• 1- and 2- year disease free survival baseline to post surgery
• To determine complete pathological response rate surgical complete response post chemotherapy, surgery and radiation
• Pharmacology toxicity every cycle
• Time to objective tumor response baseline to response of tumor
• Time to progressive disease baseline to measured progressive disease
• Overall survival baseline to date of death from any cause

Inclusion Criteria

• Histological proven diagnosis of stages I to III mesothelioma of the pleura.
• Adequate organ function including the following: adequate bone marrow reserve, hepatic, renal, pulmonary and cardiac functions.
• No prior systemic chemotherapy
• No previous surgical resection of mesothelioma, with the exception of previous chemical pleurodesis.
• No previous radiation therapy.

Exclusion Criteria

• Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
• Serious concomitant systemic disorders
• Second active primary malignancy
• Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents for a 5-day period
• Inability or unwillingness to take folic acid, vitamin B12 supplementation, or dexamethasone

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Eli Lilly and Company
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon – Fri from 9 AM to 5 PM Eastern Time (UTC/GMT – 5 hours, EST), or speak with your personal physician.

Overall Clinical Trial Officials and Contacts
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon – Fri 9 AM – 5 PM Eastern time (UTC/GMT – 5 hours, EST) Study Chair Eli Lilly and Company

Overall Contact: They may be multiple sites in this clinical trial 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559

Additional Information

Information obtained from ClinicalTrials.gov on April 15, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00192010

Study ID Number: 8848

ClinicalTrials.gov Identifier: NCT00192010

Labels: ClinicalTrial

posted by Your Attorney at 3:39 PM
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Decitabine and FR901228 in Treating Patients With Advanced Lung Cancer, Esophageal Cancer, Pleural Mesothelioma, or Lung Metastases

Date First Received: July 8, 2002
Last Updated: December 25, 2007
Clinical Trial Phase: Phase 1 Start Date: May 2002
Overall Status: Recruiting
Estimated Enrollment: 40

Intervention(s)

• Drug: celecoxib
• Drug: decitabine
• Drug: romidepsin
• Procedure: chemosensitization/potentiation therapy
• Procedure: chemotherapy
• Procedure: enzyme inhibitor therapy

Rationale

Drugs used in chemotherapy, such as decitabine and FR901228, use different ways to stop tumor cells from dividing so they stop growing or die. Using more than one drug may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of decitabine and FR901228 in treating patients with unresectable advanced lung cancer, esophageal cancer, pleural mesothelioma, or lung metastases.

Study Type: Interventional

Study Design: Treatment

OBJECTIVES
- Determine the pharmacokinetics, toxicity, and maximum tolerated dose of decitabine and FR901228 (depsipeptide) in patients with unresectable pulmonary, esophageal, or pleural malignancies.

- Determine serologic response to NY-ESO-1 in these patients before and after receiving this regimen.

- Evaluate apoptosis in tumor biopsies of these patients before and after receiving this regimen.

OUTLINE: This is a dose-escalation study.

Patients receive decitabine IV continuously on days 1-3 and FR901228 (depsipeptide) IV over 4 hours on days 4 and 10. Courses repeat every 33-36 days in the absence of disease progression or unacceptable toxicity.
Sequential dose escalation of decitabine is followed by sequential dose escalation of FR901228. Cohorts of 3-6 patients receive escalating doses of decitabine and then FR901228 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
Once the MTD is determined, two additional cohorts (6 lung cancer and 6 mesothelioma patients) receive decitabine and FR901228 as above at the MTD. These patients also receive oral celecoxib twice daily on days 4-34 of each course.

PROJECTED ACCRUAL: A maximum of 40 patients will be accrued for this study within 10.8-13.5 months.

DISEASE CHARACTERISTICS

• Histologically or cytologically confirmed primary small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), advanced esophageal cancer, or pleural mesothelioma
• Cancers of non-thoracic origin with metastases to the lungs or pleura eligible
• Unresectable disease
• Primary or metastatic disease must be accessible for biopsy by endoscopic or percutaneous fine-needle aspiration techniques
• No limited stage SCLC or operable NSCLC
• No active intracranial or leptomeningeal metastases
• Patients with prior intracranial metastases that have been treated with prior surgery or radiotherapy are eligible provided there is no evidence of active disease and no requirement for anticonvulsant therapy or steroids after treatment

PATIENT CHARACTERISTICS

Age: 18 and over
Performance status: ECOG 0-2
Life expectancy: At least 3 months
Hematopoietic:
• Absolute neutrophil count at least 1,500/mm^3 (without cytokine support)
• Platelet count greater than 100,000/mm^3 (without transfusion)

Hepatic:
• Bilirubin less than 1.5 times upper limit of normal
• PT normal

Renal:
• Creatinine no greater than 1.6 mg/dL OR
• Creatinine clearance greater than 70 mL/min

Cardiovascular:

• LVEF less than 50% by MUGA scan or echocardiogram
• No New York Heart Association class III or IV heart disease (i.e., decompensated heart failure)
• No myocardial infarction within the past year
• No uncontrolled arrhythmias
• No prior serious ventricular arrhythmias not controlled by coronary artery bypass surgery
• No prosthetic heart valves requiring anticoagulation
• No deep venous thrombosis
• No left ventricular hypertrophy
• No history of sustained ventricular tachycardia, ventricular fibrillation, Torsades de
• Pointes, or cardiac arrest without currently having an automatic implantable cardioverter defibrillator in place
• No congenital long QT syndrome or QTc > 480 msec
• No Mobitz II second degree block without currently having a pacemaker in place
• No cardiac arrhythmias requiring antiarrhytmic medication except a beta blocker or calcium channel blocker
• No hypertrophic or restrictive cardiomyopathy from prior treatment of other causes
• No uncontrolled hypertension (i.e., blood pressure ≥160/95)
• No clinically significant active myocardial ischemia on the basis of nuclear imaging or angiography
• No history of coronary artery disease (e.g., angina Canadian Class II-IV or positive stress imaging study)
• No evidence of cardiac ischemia (e.g., ST depression greater than or equal to 2 mm)

EKG

• First degree or Mobitz second degree block, bradyarrhythmias, or sick sinus syndrome allowed provided patient undergo Holter monitoring and cardiac evaluation

Pulmonary:

• FEV_1 and DLCO greater than 30% predicted
• Partial pressure of carbon dioxide (pCO_2) less than 50 mm Hg on room air
• Partial pressure of oxygen (pO_2) greater than 60 mm Hg on room air
• No pulmonary embolism

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infections
• HIV negative

PRIOR CONCURRENT THERAPY

Biologic therapy:

• At least 30 days since prior anticancer biologic therapy

Chemotherapy:

• At least 30 days since prior anticancer chemotherapy
• Prior decitabine or FR901228 (depsipeptide) allowed provided no dose-limiting toxicity was experienced at the scheduled dose

Endocrine therapy:

• See Disease Characteristics

Radiotherapy:

• See Disease Characteristics
• At least 14 days since prior localized radiotherapy to non-target lesions and recovered
• At least 30 days since prior anticancer radiotherapy

Surgery:

• See Disease Characteristics

Other:

• No more than 2 prior systemic cytotoxic treatment regimens
• At least a 5 half-life washout period since and no concurrent medication causing corrected QT interval (QTc) prolongation
• No concurrent medication causing corrected QTc prolongation
• No concurrent anticonvulsants
• No concurrent hydrochlorothiazide diuretics
• No concurrent digitalis

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: National Cancer Institute (NCI)
NCI – Center for Cancer Research
Bethesda Maryland 20892 United States
Warren Grant Magnuson Clinical Center – NCI Clinical Trials Referral Office
Bethesda Maryland 20892-1182 United States

Overall Clinical Trial Officials and Contacts
David S. Schrump, MD Study Chair NCI – Surgery Branch

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00041158
Study ID Number: CDR0000069448
ClinicalTrials.gov Identifier: NCT00041158

Labels: ClinicalTrial

posted by Your Attorney at 3:37 PM
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Study of Pemetrexed in Mesothelioma and Lung Cancer Patients With Fluid Around the Lungs or Abdomen

Last Updated: January 21, 2008
Clinical Trial Phase: Phase 2 Start Date: December 2006
Overall Status: Recruiting
Estimated Enrollment: 30

Condition Keyword(s):
• Non-Small Cell Lung Cancer
• Mesothelioma
• Lung Neoplasms

Intervention(s):
• Drug: pemetrexed

Rationale

This study will test the effects of pemetrexed on mesothelioma and lung cancer patients with fluid around their lungs or abdomen.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety Study

Outcome Measures for this Clinical Trial

Primary: Pharmacology toxicity every cycle

Secondary:
• Adverse events every cycle
• Pharmacokinetics cycle 1, cycle 2
• Pemetrexed dosing recommendations every cycle

Inclusion Criteria

• Diagnosis of locally advanced or metastatic (Stage III or IV at entry) non-small cell lung cancer or mesothelioma

• Presence of third-space fluid (fluid around the lungs or abdomen).

• Measurable lesions are not required for enrollment in this study.

• Prior anticancer treatment (except radiation) must be completed at least 3 weeks prior to study enrollment, and the patient must have recovered from the sharp toxic effects the anticancer treatment.

• Estimated life expectancy of at least 8 weeks.

Exclusion Criteria

• Have received treatment within the last 30 days with a drug that was not a marketed product

• Active infection that, in the opinion of the investigator, would not allow the patient to tolerate therapy.

• Pregnancy.

• Breast-feeding.

• Significant weight loss (that is, greater than or equal to 10% of body weight) over the 6 weeks before study entry.

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Eli Lilly and Company
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon – Fri from 9 AM to 5 PM Eastern Time (UTC/GMT – 5 hours, EST), or speak with your personal physician.
København 2100 Denmark

Overall Clinical Trial Officials and Contacts
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon – Fri 9 AM – 5 PM Eastern time (UTC/GMT – 5 hours, EST) Study Director Eli Lilly and Company

Overall Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00316225
Study ID Number: 10426
ClinicalTrials.gov Identifier: NCT00316225

Labels: ClinicalTrial

posted by Your Attorney at 3:34 PM
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Phase I Dose-Escalation Study Of Azacitidine In Combination With Temozolomide

Date First Received: February 26, 2008
Last Updated: March 5, 2008
Verified by: Columbia University, February 2008
Clinical Trial Phase: Phase 1 Start Date: October 2007
Overall Status: Recruiting
Estimated Enrollment: 24

Condition Keyword(s):Soft Tissue Sarcoma; Mesothelioma

Intervention(s): Drug: Azacitidine In Combination With Temozolomide

Rationale

The purpose of this study is to determine safety and toxicity for the combination of Temozolomide and Azacitidine in the treatment of Advanced Soft Tissue Sarcoma or Malignant Mesothelioma. This is a single-center, open-label, single-arm Phase I dose-escalation trial.

Patients will be evaluated with complete history and physical as well as laboratory studies (complete blood count, metabolic panel, liver function tests), biopsy, and imaging of all sites of measurable disease. This study will be conducted over the course of 3 years.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety Study

The primary objective of the study is to determine the clinical and laboratory toxicities as well as acceptability/tolerance of this dose schedule of combined drug treatment with temozolomide and azacitidine.

Secondary objectives include determination of biochemical response to azacitidine as defined as change in methylation status. We will specifically be looking at changes in genome wide methylation patterns as determined by two high-throughput platforms:

1. A single nucleotide polymorphism chip-based method (MSNP) for genome wide epigenetic profiling

2. CpG island promoter arrays will be performed to focus on promoter methylation status.

We will also monitor clinical response, time to progression and overall survival.

Outcome Measures for this Clinical Trial

Primary: The primary endpoint is dose limiting toxicity. Study Completion

Secondary: Clinical response, time to progression and overall survival. Study Completion

Inclusion Criteria

• Histologically confirmed soft tissue sarcoma or mesothelioma.
• Ineligible for other high priority national or institutional study.
• Non-pregnant, non-lactating.
• Recurrent or progressive disease defined as an increase in size of any existing tumor mass, or the development of new tumor mass or masses, which is not amenable to definitive surgical therapy.
• Measurable disease defined as lesions that can be measured in at least one dimension by physical examination or by means of medical imaging techniques. Ascites and pleural effusions will not be considered measurable disease.
• Prior chemotherapy is allowed with the exception of prior treatment with Temozolomide or Azacitidine. Patients must have received prior 1st line therapy. There is no upper limit to the number of prior therapies received. Prior treatment with an alkylating agent is acceptable.
• Prior radiation therapy is allowed.
• At least 4 weeks since prior chemotherapy or at least 6 weeks since prior radiation therapy.
• Patients may have had another cancer but there must be convincing clinical evidence that the sarcoma is the disease requiring therapeutic intervention. (i.e. Several sarcoma patients have had had a prior cancer [Hodgkin's disease or breast cancer] treated years previously and then developed a clinically active sarcoma.)
• Clinical parameters: Life expectancy > 3 months, Age > 18 years, Performance
• Karnofsky performance status of greater than or equal to 60%.
• Required initial laboratory data:
  • Absolute neutrophil count > 1,500/mm3
  • Hemoglobin > 10.0 g/dl
  • Platelet count > 100,000/mm3
  • Total Bilirubin
  • Transaminases: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels must be
  • Serum creatinine levels
• Women of child-bearing potential must have a negative serum pregnancy test prior to initiation of treatment.
• Men and women of child-bearing potential must be willing to consent to using effective contraception while on treatment and for a reasonable period thereafter (approximately 3 months).
• Capable of providing written, informed consent. Each patient must be completely aware of the nature of his/her disease process and must willingly give consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks and discomforts.
• No serious medical or psychiatric illness preventing informed consent or intensive treatment (e.g. serious infection).
• No uncontrolled central nervous system metastases.

Exclusion Criteria

• Known or suspected hypersensitivity to azacitidine or mannitol
• Pregnant or breast-feeding
• Histology other than soft-tissue sarcoma or mesothelioma
• Active or uncontrolled infection or other serious systemic disease
• Prior treatment with temozolomide or azacitidine
• Pregnant or lactating women
• Uncontrolled central nervous system metastases
• Liver metastases
• Patients will not be excluded if they do not wish to participate in the second biopsy for tissue evaluation
• Subjects who have not had prior chemotherapy.

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Columbia University
Columbia University Medical Center
New York New York 10032 United States

Overall Clinical Trial Officials and Contacts: Robert N Taub, MD Principal Investigator Columbia University Medical Center

Overall Contact: Lilian Batista, BS 212-305-6837 lb2327@columbia.edu

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00629343

Study ID Number: AAAC3255

ClinicalTrials.gov Identifier: NCT00629343

Labels: ClinicalTrial

posted by Your Attorney at 3:30 PM
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N-AcetylCysteine vs. Placebo to Prevent Neurotoxicity Induced by Platinum Containing Chemotherapy

N-AcetylCysteine vs. Placebo to Prevent Neurotoxicity Induced by Platinum Containing Chemotherapy

In this study we want to investigate the efficacy of N-acetylcysteine (NAC), which is an anti-oxidant, in the prevention of cisplatin-induced neural toxicity, in patients treated for lung cancer with chemotherapy containing cisplatin…

Date First Received: March 11, 2008

Last Updated: March 17, 2008

Verified by: Rijnstate Hospital, March 2008

Clinical Trial Phase: N/A | Start Date: March 2008

Overall Status: Not yet recruiting

Estimated Enrollment: 50 a

Brief Summary

Official Title: “A Randomized Double-Blind Study of N-AcetylCysteine vs. Placebo to Prevent Neurotoxicity Induced by Platinum Containing Chemotherapy in Patients Treated for (Non)Small Cell Lung Cancer and Malignant Mesothelioma”

Condition Keyword(s):

• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Small Cell Lung
• Mesothelioma

Intervention(s):

• Drug: N-Acetylcysteine
• Drug: Placebo

In this study we want to investigate the efficacy of N-acetylcysteine (NAC), which is an anti-oxidant, in the prevention of cisplatin-induced neural toxicity, in patients treated for lungcancer with chemotherapy containing cisplatin.

Study Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Detailed Clinical Trial Description

Background of the study: Cisplatin (CDDP) is a major compound in chemotherapy in patients with non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC) and malignant mesothelioma. Cisplatin is associated with a number of side-effects, one of which is neurotoxicity. For a number of patients this neurotoxicity is a dose-limiting side-effect. At this point no measures are taken to prevent the occurrence of neurotoxicity during treatment with cisplatin. Recent studies have shown that the association of anti-oxidants to the treatment with cisplatin has a neuroprotective effect without loss of anti-tumour efficacy of cisplatin. One of these anti-oxidants is glutathione (GSH), this is a natural anti-oxidant that is synthesized in all cells, mainly in the liver and the muscles. This GSH plays a central role in the pathophysiology (of efficacy and of side-effects) of cisplatin. We want to investigate the efficacy of N-acetylcysteine (NAC), which serves as a substrate for the synthesis of GSH, in the prevention of cisplatin-induced neurotoxicity.

Objective of the study: The primary objective is to establish the neuroprotective efficacy of NAC against cisplatin-induced neurotoxicity. Mainly the sensory neuronal guidance will be assessed before and after treatment with cisplatin in a group of patients receiving NAC compared to a control-group receiving placebo. – The secondary objectives are establishing the protective effect of NAC regarding other cisplatin-induced side-effects such as haematological pathology (anaemia, leucopenia, thrombopenia, febrile neutropenia), loss of creatinine clearance and occurrence of liver-chemistry abnormalities. Secondary objectives include also establishing the effect on tumour response, clinical performance (Karnofski performance index) and quality of life.

Study design: Monocenter, non-academical teaching hospital, double-blind randomized placebo-controlled study.

Study population: 50 Consecutive patients, who will receive at least 4 cycles of cisplatin in the treatment of NSCLC, SCLC and malignant mesothelioma, will be admitted, irrespective of the disease stage.

Intervention: Patients will be randomized in a placebo-arm and a NAC-arm. They will receive oral study-medication (NAC or placebo) three times a day and they will receive intravenous study-medication every 3 weeks, each time 6 hours after the completion of the cisplatin-infusion.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness

Burdens: Patients will have to take study-medication 3 times daily for the whole period of treatment. The other burden is the electromyographic (EMG) testing, which will normally take place 3 times during the course of the whole treatment, therefore patients will have to visit the hospital to be measured. To minimize this burden, the EMG-measurements will be planned on the same day, the patient has to visit the hospital for reasons regarding his/her regular chemotherapy-treatment. Only surface patch electrodes will be used (no needle electrodes). All other information will be obtained from the patients’ files (blood samples, physic evaluations, etc) these are considered to be part of the routines of treatment. Patients will have to fill in Quality of Life questionnaires.

Risks: oral NAC is a well known drug, used for over thirty years, that is well tolerated even if dosed at 600 mg three times daily. For intravenous NAC, allergic reactions have been reported. There is also a theoretical risk, that NAC may reduce anti-tumour efficacy of cisplatin, this risk will be theoretically ruled out by appropriate dosing of NAC. After inclusion of the first 30 patients an interim analysis will be performed regarding the tumour response.

Benefits: NAC will possibly prevent the occurrence of neurotoxicity, improving quality of life. This may, in turn, result in less probability of dose-reductions and of pre-term arrest of treatment.

Outcome Measures for this Clinical Trial

Primary:

• The occurrence of peripheral neuropathy: with the peripheral neuropathy score (PNP-score) and the electrophysiological measurements. 5 months

Secondary:

• haematological abnormalities 5 months
• creatinine clearance. 5 months
• liver chemistry abnormalities 5 months
• Karnofski Performance Score 5 months
• Quality of life 5 months

Criteria for Participation in this Clinical Trial

Inclusion Criteria:

• diagnose is histologically or cytologically proven (NSCLC,SCLC), malignant mesothelioma (histologically)
• at least 4 cycles of cisplatin are planned
• adequate renal function (creatinine clearance as calculated by Cockroft-Gault method >
• 60 ml/min)
• Karnofski performance score > 60 %
• written informed consent
• patient must be able to comply with study measurements i.e. hospital visits for EMG and QoL assessments
• age ≥ 18 years

Exclusion Criteria:

• patients with pre-existing neuropathy
• patients not willing to stop earlier prescribed NAC
• patients not willing to stop vitamins E and A above daily advisory dosage
• uncontrolled metastasis in the central or peripheral nervous system

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Rijnstate Hospital

Rijnstate Hospital

Arnhem Gelderland 6800TA Netherlands

Overall Clinical Trial Officials and Contacts

Idris Bahce, MD Principal Investigator Rijnstate Hospital

Overall Contact: Idris Bahce, M.D. +31263788888 IBahce@alysis.nl

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00637624

Study ID Number: LTC-510-100108-Bahce

ClinicalTrials.gov Identifier: NCT00637624

Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

posted by Your Attorney at 3:28 PM
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Carboplatin, Bevacizumab and Pemetrexed in the First-Line Treatment of Patients With MPM

Carboplatin, Bevacizumab and Pemetrexed in the First-Line Treatment of Patients With MPM

The purpose of this research study is to evaluate how effective the combination of Carboplatin, Bevacizumab (Avastin™) and, Pemetrexed (Alimta™) is in the treatment of patients with Malignant Pleural Mesothelioma (MPM). A combination of cisplatin and pemetrexed is considered standard for this disease and typically off protocol patients would receive cisplatin or carboplatin and pemetrexed…

Date First Received: January 17, 2008

Last Updated: January 29, 2008

Verified by: H. Lee Moffitt Cancer Center and Research Institute, January 2008

Clinical Trial Phase: Phase 1/Phase 2 | Start Date: October 2007

Overall Status: Recruiting

Estimated Enrollment: 48

Brief Summary

Official Title: “Phase I/II Trial of Carboplatin, Bevacizumab and Pemetrexed in the First-Line Treatment of Patients With Malignant Pleural Mesothelioma (MPM)” Condition

Keyword(s):

• Mesothelioma Intervention(s):

• Drug: Carboplatin, Bevacizumab and Pemetrexed

The purpose of this research study is to evaluate how effective the combination of Carboplatin, Bevacizumab (Avastin™) and, Pemetrexed (Alimta™) is in the treatment of patients with Malignant Pleural Mesothelioma (MPM). A combination of cisplatin and pemetrexed is considered standard for this disease and typically off protocol patients would receive cisplatin or carboplatin and pemetrexed as standard of care.

Primary: Determine the Overall Survival (OS), (median survival(MS) and 1-yr survival (1-yr S)), in newly diagnosed patients with MPM who are treated with a regimen consisting of cisplatin, bevacizumab, and pemetrexed. Patients will be followed until death and survival curves will be generated. Response rates will be assessed.

Secondary: Estimate the progression free survival (PFS) – Determine the response rates – Safety of the regimen will also be assessed. The planned length of the study (first subject screened to last subject enrolled) is 24 months. The planned length of the entire study (enrollment period + the treatment period + a follow-up period of at least 12 months) is 36 months.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study

Detailed Clinical Trial Description

A blood sample will be taken to check the patient’s blood and platelet counts before each Pemetrexed dose. Before each cycle, we will review the patient’s medical history, give them a physical exam (including vital signs: blood pressure, heart rate, breathing rate, temperature), and check their weight, performance status and blood. The patient’s tumor will be measured after every other cycle. The patient’s urine will be tested before every other cycle with Bevacizumab.

Treatment Regimen: To ensure the safety, before initiating the phase II dose, we will have a brief phase I portion, where tiered dose escalation to the anticipated phase II dose will occur.

Tier I Carboplatin at AUC of 5 Bevacizumab 15 mg/Kg I.V. on day 1 Pemetrexed 500 mg/m2 on day 1 Every 21 days

Tier II (Target dose) Carboplatin at AUC of 6 Bevacizumab 15 mg/Kg I.V. on day 1 Pemetrexed 500 mg/m2 on day 1 Every 21 days

Tier (-1) Carboplatin at AUC of 4 Bevacizumab 15 mg/Kg I.V. on day 1 Pemetrexed 500 mg/m2 on day 1 Every 21 days

With each cycle, we will give the following: Folic Acid 300 µg to 1 mg orally once daily starting day 1. B12 injections given subcutaneously any time between days -7 to 1 of the first cycle and then every 9 weeks.

Dexamethasone 4mb BID on day-1,0, and day +1

Patients will be enrolled in cohorts of three. If one of the three patients has a dose limiting toxicity (DLT) then three additional patients will be enrolled. If no DLTs occur then patients will be accrued in the next dose level. If two DLTs occur in a cohort of three patients or in an expanded cohort of 6 patients then that dose level will be called the Maximum Administered Dose (MAD). A dose level below will be called the MTD and will be the recommended dose for further phase II testing. Al three patients in a cohort must complete one full cycle, before proceeding to the next cohort.

DLT will be defined as grade 4 neutropenia, febrile neutropenia, and any grade 3 or 4 non-hematologic toxicity except for alopecia and nausea/vomiting/diarrhea without adequate prophylaxis. (CTC version 3.0).

No further dose escalation will be attempted beyond dose Tier 2. If there are no dose-limiting toxicities in dose Tier 2 then this will be considered the phase II dose. If there is a DLT in dose Tier 1 then we will enroll 3 patients in Tier -1 and if no further DLTs occur then Tier -1 will be the phase II dose.

When the patient goes off-study, they will have a physical exam, tumor measurements, and blood test evaluations.

Each study patient will be contacted every 3 months for the rest of their life. Information about any extra treatments they have received will be collected and recorded if they are taken off-study because their disease got worse. If they are taken off-study for any other reason, we will collect information on any extra anti-cancer treatments they have received for Malignant Pleural Mesothelioma (MPM).

Outcome Measures for this Clinical Trial

Primary:

• Determine if Overall Survival (OS) in newly diagnosed patients with MPM who are treated first-line with a regimen consisting of carboplatin, bevacizumab, and pemetrexed exceeds 12 months. 36 months

Secondary:

• Estimate the progression free survival (PFS). Determine the response rates. Safety of the regimen will also be assessed. Patient will be taken off the study at the time of progression.

Criteria for Participation in this Clinical Trial

Inclusion Criteria:

• Patient must have histologically proven diagnosis of Malignant Pleural Mesothelioma (MPM)
• Patient must have MPM with measurable disease.
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Patient must have adequate renal function with a serum creatinine level of less than 1.5 mg/dl and patient should have a calculated creatinine clearance of more than 40ml/min.
• Patient must have adequate hepatic function with a serum bilirubin level of less that 3mg/dl, and an alkaline phosphatase, ALT and AST of less than five times the upper limit of normal
• Patient must also have evidence of adequate bone marrow function with an absolute neutrophil count of more than 1500 cells per deciliter and a platelet count of more than 100,000 per deciliter.
• Patients must be more than 28 days since prior open biopsy; more than 7 days since prior fine-needle aspiration; more than 7 days since prior core biopsy; more than 28 days since prior surgery.
• Patients must be able to take dexamethasone, folic acid, and vitamin B-12 supplementation.
• All patients must sign informed consent that will detail the investigational nature of the study in accordance with the institutional and federal guidelines.
• Patients with clinically significant pleural effusions or ascities (symptomatic or detectable by clinical exam) should have their effusions drained prior to enrollment on the clinical trial.

Exclusion Criteria:

• Patients with hypercalceamia (corrected calcium of more than 11 mg/dl) will be excluded.
• Patients with history of hemoptysis, hemetemesis, coagulopathy or thrombosis will be excluded.
• Patients requiring anticoagulation for any reason will be excluded.
• History of palliative radiation therapy within 2 weeks
• Blood pressure of >160/100 mmHg, despite adequate anti-hypertensive use.
• Currently ongoing unstable angina
• New York Heart Association (NYHA) Grade II or greater congestive heart failure.(Please see Appendix III.)
• History of stroke within 6 months
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to the day of initiation of treatment, anticipation of need for major surgical procedure during the course of the study
• Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to the day of initiation of treatment.
• Pregnant (positive pregnancy test) or lactating
• Urine calculated creatinine clearance of less than 40ml/minute. (Please see Appendix VI).
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0
• Serious, non-healing wound, ulcer, or bone fracture
• Inability to comply with study and/or follow-up procedures

Laboratory Values:

• Patient must have adequate renal function with a serum creatinine level of less than 1.5 mg/dl and patient should have a calculated creatinine clearance of more than 40ml/min.
• Patient must have adequate hepatic function with a serum bilirubin level of less than 3 mg/dl, and an alkaline phosphatase, ALT and AST of less than five times the upper limit of normal
• Patient must also have evidence of adequate bone marrow function with an absolute neutrophil count of more than 1, 500 cells per deciliter and a platelet count of more than 100,000 per deciliter.

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: H. Lee Moffitt Cancer Center and Research Institute

H. Lee Moffitt Cancer Center & Research Institute

Tampa Florida 33612 United States

Overall Clinical Trial Officials and Contacts

Roohi Ismail-Khan, M.D. Principal Investigator H. Lee Moffitt Cancer Center and Research Institute

Overall Contact: Melissa Joiner, R.N. 813-745-1896 melissa.joiner@moffitt.org

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00604461

Study ID Number: MCC-14896

ClinicalTrials.gov Identifier: NCT00604461

Health Authority: United States: Institutional Review Board

Moffitt Cancer Center Clinical Trials website

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

posted by Your Attorney at 3:25 PM
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FR901228 and Flavopiridol in Treating Patients With Advanced Lung, Esophageal, or Pleural Cancer

FR901228 and Flavopiridol in Treating Patients With Advanced Lung, Esophageal, or Pleural Cancer

RATIONALE: Drugs used in chemotherapy, such as FR901228 and flavopiridol, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving FR901228 together with flavopiridol may kill more tumor cells.

Date First Received: December 7, 2004

Last Updated: February 27, 2008

Verified by: National Cancer Institute (NCI), September 2007

Clinical Trial Phase: Phase 1 | Start Date: November 2004

Overall Status: Recruiting

Estimated Enrollment: 48

Brief Summary

Official Title: “Phase I Study Of Sequential Depsipeptide/Flavopiridol Infusion for Malignancies Involving Lungs, Esophagus, Pleura or Mediastinum”

Condition Keyword(s):

• Esophageal Cancer
• Lung Cancer
• Malignant Mesothelioma
• Metastatic Cancer

Intervention(s):

• Drug: alvocidib
• Drug: romidepsin
• Procedure: chemosensitization/potentiation therapy
• Procedure: chemotherapy
• Procedure: enzyme inhibitor therapy

PURPOSE: This phase I trial is studying the side effects and best dose of FR901228 when given together with flavopiridol in treating patients with advanced lung, esophageal, or pleural cancer.

Study Type: Interventional

Study Design: Treatment

Detailed Clinical Trial Description

OBJECTIVES:

• Primary – Determine the maximum tolerated dose and dose-limiting toxic effects of FR901228 (depsipeptide) when administered with flavopiridol in patients with advanced primary lung or esophageal cancer, malignant pleural mesothelioma, or lung or pleural metastases. – Determine the pharmacokinetics of this regimen in these patients.
• Secondary – Analyze gene expression in laser-captured tumor cells, buccal mucosa, and peripheral blood mononuclear cells of these patients before and after treatment with this regimen. – Analyze mcl-1 protein expression and apoptosis in tumor biopsies from these patients before and after treatment with this regimen.

OUTLINE: This is a dose-escalation study of FR901228 (depsipeptide).

Patients receive FR901228 IV over 4 hours followed by flavopiridol IV continuously over 72 hours beginning on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of FR901228 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Six additional patients receive treatment at the MTD.

PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study within 1-2 years.

Criteria for Participation in this Clinical Trial

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed advanced malignancy of 1 of the following types:
• Primary small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC)
• No limited-stage SCLC or operable NSCLC
• Esophageal cancer
• Inoperable disease
• Malignant pleural mesothelioma
• Epithelial thymoma
• Cancer of nonthoracic origin with metastases to the lungs or pleura
• No potentially treatable pulmonary metastases from lymphomas or germ cell tumors
• Tumor must be amenable to biopsy by endoscopic or percutaneous fine needle aspiration techniques
• Chemonaïve patients allowed provided they refused potentially effective first-line chemotherapy
• Intracranial or leptomeningeal metastases allowed provided the following are true:
• Treated by surgery or radiotherapy
• No evidence of active disease
• No requirement for anticonvulsant therapy or steroids

PATIENT CHARACTERISTICS:

• Age – 18 and over
• Performance status – ECOG 0-2
• Life expectancty – At least 3 months
• Hematopoietic
• Platelet count > 100,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3 (transfusion and cytokine independent)
• Hepatic
• PT normal
• Bilirubin
• AST and ALT ≤ 1.5 times ULN
• Renal
• Creatinine ≤ 1.6 mg/dL OR
• Creatinine clearance > 70 mL/min
• Cardiovascular
• No myocardial infarction within the past 6 months
• Ejection fraction ≥ 45%
• QTc ≤ 500 msec
• No unstable angina
• No cardiac ischemia
• No left ventricular hypertrophy
• No deep venous thrombosis requiring anticoagulation within the past 6 months
• No known cardiac abnormalities including any of the following:
• Uncontrolled arrhythmias
• History of sustained ventricular tachycardia, ventricular fibrillation, Torsades de Pointes, or cardiac arrest without an automatic implantable cardioverter defibrillator in place
• Congenital long QT syndrome or QTc > 480 msec
• Mobitz II second degree block without a pacemaker in place
• Any cardiac arrhythmia requiring antiarrhythmic medication
• Beta blockers and calcium channel blockers allowed
• New York Heart Association class II or IV decompensated heart failure
• Left ventricular ejection fraction
• Hypertrophic or restrictive cardiomyopathy from prior treatment or other causes
• Left ventricular hypertrophy
• Uncontrolled hypertension (i.e., blood pressure ≥ 160/95)
• Myocardial infarction within the past year
• Clinically significant active myocardial ischemia by nuclear imaging or angiography
• History of coronary artery disease (e.g., Canadian class II-IV angina or positive stress imaging study)
• Pulmonary
• FEV_1 and DLCO > 30% of predicted
• pCO_2
• pO_2 > 60 mm Hg by ABG on room air
• No pulmonary embolism requiring anticoagulation within the past 6 months
• Other
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infection
• HIV negative

PRIOR CONCURRENT THERAPY:

• Biologic therapy
• At least 30 days since prior biologic therapy for the malignancy
• No concurrent cytokine support
• Chemotherapy
• See Disease Characteristics
• Prior FR901228 (depsipeptide) or flavopiridol allowed provided patient did not experience dose-limiting toxicity at the dose they are scheduled to receive on study
• At least 30 days since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) for the malignancy
• Endocrine therapy
• See Disease Characteristics
• • Radiotherapy
• See Disease Characteristics
• At least 30 days since prior radiotherapy for the malignancy
• At least 14 days since prior localized radiotherapy to non-target lesions and recovered
• Surgery
• See Disease Characteristics
• Other
• No more than 2 prior systemic cytotoxic treatment regimens
• No concurrent hydrochlorothiazide
• No concurrent digoxin

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: National Cancer Institute (NCI)

NCI – Center for Cancer Research

Bethesda Maryland 20892 United States

Warren Grant Magnuson Clinical Center – NCI Clinical Trials Referral Office

Bethesda Maryland 20892-1182 United States

Overall Clinical Trial Officials and Contacts

David S. Schrump, MD Study Chair NCI – Surgery Branch

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00098644

Study ID Number: CDR0000398184

ClinicalTrials.gov Identifier: NCT00098644

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute’s PDQ® database

Featured trial article

Web site for additional information

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

posted by Your Attorney at 3:23 PM
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Study of Safety and Tolerability of Intravenous CRS-207 in Adults With Selected Advanced Solid Tumors Who Have Failed or Who Are Not Candidates for St

Study of Safety and Tolerability of Intravenous CRS-207 in Adults With Selected Advanced Solid Tumors Who Have Failed or Who Are Not Candidates for Standard Treatment

Date First Received: December 22, 2007

Last Updated: April 23, 2008

Verified by: Anza Therapeutics, Inc., April 2008

Clinical Trial Phase: Phase 1 | Start Date: December 2007

Overall Status: Recruiting

Estimated Enrollment: 30

Brief Summary

Official Title: “A Phase 1, Open-Label, Dose-Escalation, Multiple Dose Study of the Safety, Tolerability, and Immune Response of CRS-207 in Adult Subjects With Selected Advanced Solid Tumors Who Have Failed or Who Are Not Candidates for Standard Treatment”

Condition Keyword(s):

• Malignant Epithelial Mesothelioma
• Adenocarcinoma of the Pancreas
• Carcinoma, Non-Small-Cell Lung
• Adenocarcinoma of the Ovaries

Intervention(s):

• Biological: CRS-207, Live-attenuated Listeria monocytogenes expressing human Mesothelin

This clinical trial will evaluate the safety and tolerability of CRS 207 an investigational product that is a weakened form (attenuated) of Listeria monocytogenes, a type of bacteria that is commonly found in the environment. CRS-207 has been altered in the lab to reduce its ability to cause disease, while maintaining stimulation of the immune system. CRS 207 has also been genetically modified with recombinant DNA to release an antigen called Mesothelin.

Because CRS 207 stimulates an immune response to Mesothelin and Mesothelin may be present at higher levels on tumor cells than on normal cells, this clinical trial will also examine if CRS 207 boosts the immune system in a way that targets certain types of cancer.

The purpose of this first clinical trial with CRS-207 is to identify an appropriate dose of the investigation agent for later clinical studies and to explore safety when given to consenting adults with advanced cancer of the ovary or pancreas, non-small cell lung cancer, or advanced malignant epithelial mesothelioma. Immunological response to CRS-207 and tumor status of study participants will also be measured. Patients who choose to enter the study must meet all study entry criteria and must have previously failed standard treatment for their cancer. Qualifying study patients will be assigned to receive one of several dose levels of CRS-207. Each patient may receive up to 4 intravenous administrations (21 days apart) of CRS-207 at their assigned dose level.

Study Type: Interventional

Study Design: Treatment, Open Label, Single Group Assignment, Safety Study

Detailed Clinical Trial Description

Patients who consent to participate in the study will be evaluated for eligibility according to their medical history, physical examination, blood testing, and computed tomography (CT) scan of thorax, abdomen, and pelvis. Those patients who qualify for the study will receive up to 4 intravenous doses of CRS-207, 21 days apart. After each infusion, they will be monitored overnight in an in-patient facility, including collection of blood specimens. Study participants will return after each infusion for outpatient follow-up visits for further blood tests and additional monitoring of safety and immune response to CRS-207. Participants will have repeat CT scans to measure tumor size after the 2nd dose and again after the 4th dose. On Day 91 participants will be discharged from the study. All study participants will be eligible to participate in a long-term follow-up study with a visit 6 months after the final dose of CRS-207 and annually thereafter for evaluation of disease progression, survival, and potential long-term toxicity of CRS 207.

Outcome Measures for this Clinical Trial

Primary:

• Dose-limiting toxicities related to the investigational agent 28 days after first dose

Criteria for Participation in this Clinical Trial

Inclusion Criteria:

• 1. Documented malignant epithelial mesothelioma, cancer of the pancreas or ovaries or non-small-cell lung cancer (NSCLC) and who have failed (or are not candidates for) standard therapy
• 2. ECOG Performance Status of 0 to 1, or Karnofsky Performance Status (KPS) of 80-100%
• 3. Adequate organ function as defined by study-specified laboratory tests
• 4. Must use acceptable form of birth control through the study and for 28 days after final dose of study drug
• 5. Signed informed consent form
• 6. Willing and able to comply with study procedures

Exclusion Criteria:

• History of infection with Listeria, prior vaccination with a listeria-based vaccine, or a positive fecal culture of Listeria at screening
• Currently have or have history of certain study-specified heart, liver, kidney, lung, neurological, immune or other medical conditions
• Allergy to penicillin or yeast or other component of the study drug product (e.g., glycerol)
• Clinical metabolic or laboratory abnormalities defined as Grade 3 or 4 of the National Cancer Institute’s (NCI’s) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0
• Artificial (prosthetic) joint or other artificial implant or devices that cannot be easily removed
• Known coagulation (blood clotting) disorder or recent thrombotic event
• Certain types of blood transfusions within 14 days prior to receiving study drug or a condition requiring regular blood transfusions more than twice per month
• Taking the following medications: Anti-coagulation medications; Systemically active steroids for more than 2 days within 28 days prior to receiving study drug; More than 325 mg per day of aspirin; More than 2 g per day of acetaminophen; Systemic antibiotics within 14 days prior to receiving study drug; Another investigational product within 28 days prior to receiving study drug
• Major surgery or significant traumatic injury (or unhealed surgical wounds) occurring within 28 days prior to receiving study drug, or planned surgery requiring general anesthesia
• Infection with HIV, hepatitis B or C, or HTLV-1 (human t-lymphotropic virus type 1) at screening
• Pregnant or lactating, or close contact with pregnant women or newborn babies
• Conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient’s ability to comply with study visits and procedures

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Anza Therapeutics, Inc.

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University

Baltimore Maryland 21231 United States

National Cancer Institute, NCI

Bethesda Maryland 20892 United States

University of Pennsylvania Abramson Family Cancer Research Center

Philadelphia Pennsylvania 19104 United States

Mary Crowley Cancer Research Center

Dallas Texas 75201 United States

Overall Clinical Trial Officials and Contacts

Dung Thai Study Director Anza Therapeutics, Inc.

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00585845

Study ID Number: VAC07001

ClinicalTrials.gov Identifier: NCT00585845

Health Authority: United States: Food and Drug Administration

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

posted by Your Attorney at 3:20 PM
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Printed Education Materials in Patients Who Are Finishing Treatment for Stage I, Stage II, or Stage IIIA Breast Cancer, Colorectal Cancer, Prostate Ca

Printed Education Materials in Patients Who Are Finishing Treatment for Stage I, Stage II, or Stage IIIA Breast Cancer, Colorectal Cancer, Prostate Cancer, or Chest Cancer

Date First Received: September 6, 2006

Last Updated: December 25, 2007

Verified by: National Cancer Institute (NCI), October 2007

Clinical Trial Phase: Phase 3 | Start Date: May 2006

Overall Status: Recruiting

Estimated Enrollment: 332

Brief Summary

Official Title: “Efficacy and Feasibility of a Psychosocial Intervention Within the CCOP Context: Evaluation of the Facing Forward Guide to Facilitate Life After Active Cancer Treatment”

Condition Keyword(s):

• Breast Cancer
• Colorectal Cancer
• Lung Cancer
• Malignant Mesothelioma
• Prostate Cancer
• Psychosocial Effects/Treatment
• Quality of Life
• Thymoma and Thymic Carcinoma

Intervention(s):

• Procedure: educational intervention
• Procedure: psychosocial assessment and care
• Procedure: quality-of-life assessment

RATIONALE: Printed educational materials, such as the Facing Forward Series: Life After Cancer Treatment manual, may help make the transition from cancer patient to cancer survivor easier in patients who are finishing treatment for cancer. It is not yet known if the Facing Forward Series: Life After Cancer Treatment manual and The Cancer Information Service, Questions and Answers fact sheet is more effective than the The Cancer Information Service, Questions and Answers fact sheet alone in helping to make life after cancer treatment easier and to improve quality of life in patients with breast cancer, colorectal cancer, prostate cancer, or chest cancer.

PURPOSE: This randomized phase III trial is studying how well printed education materials work in assisting patients who are finishing treatment for stage I, stage II, or stage IIIA breast cancer, colorectal cancer, prostate cancer, or chest cancer to make the transition from cancer patient to cancer survivor easier.

Study Type: Interventional

Study Design: Other, Randomized, Open Label, Active Control

Detailed Clinical Trial Description

OBJECTIVES:

• Primary - Determine the efficacy of a psychoeducational intervention comprising a specific print intervention manual (Facing Forward Series: Life After Cancer Treatment [Facing Forward manual]) and a general print intervention fact sheet (The Cancer Information Service, Questions and Answers) vs the general print intervention fact sheet only on the uptake of recommended actions (e.g., developing a wellness plan after treatment, dealing with pain and fatigue, finding support groups to deal with feelings after treatment, and dealing with family issues after treatment) in patients completing active treatment for stage I-IIIA breast, prostate, colorectal, or thoracic cancer. – Explore patient process evaluations of the Facing Forward manual in terms of its usability, comprehension, and satisfaction.
• Secondary - Examine psychological outcomes (i.e., depressive symptoms, fear of recurrence, health-related quality of life, and self-efficacy) as a function of exposure to the Facing Forward manual.

OUTLINE: This is a multicenter, randomized, controlled, open-label, cohort study. Patients are stratified according to participating center, prior chemotherapy (yes vs no), and type of cancer (breast vs colorectal vs prostate vs thoracic). Patients are randomized to 1 of 2 treatment arms.

• Arm I (intervention): Patients receive a specific print intervention manual entitled Facing Forward Series: Life After Cancer Treatment and a general print intervention fact sheet entitled The Cancer Information Service, Questions and Answers.
• Arm II (control): Patients receive the general print intervention fact sheet entitled The Cancer Information Service, Questions and Answers.

In both arms, patients are evaluated at baseline (within 18 days of the patient’s final cancer treatment visit), 8 weeks (via mailed home materials), and then at 6 months (via mailed home materials). Baseline evaluations include background information (i.e., demographics and medical status), baseline use of educational materials, survivorship activities, and psychological factors (i.e., depressive symptoms, quality of life, fear of recurrence, and self-efficacy). Psychological factors are also reassessed at 8 weeks and 6 months, as well as use of educational materials and survivorship activities.

For patients in both arms, uptake of recommended actions are reassessed. Patients in arm I complete ratings of the Facing Forward Series: Life After Cancer Treatment manual usability, comprehension, and satisfaction at 8 weeks and 6 months.

PROJECTED ACCRUAL: A total of 332 patients will be accrued for this study.

Outcome Measures for this Clinical Trial

Primary:

• Uptake of recommended actions
• Number of sections of the Facing Forward manual read with satisfaction and comprehension

Secondary:

• Changes in psychological outcomes from baseline to 8-week follow-up

Criteria for Participation in this Clinical Trial

DISEASE CHARACTERISTICS:

• Diagnosis of breast, colorectal, prostate, or thoracic cancer*
• Stage I-III disease
• Approaching, attending, or already attended with the past 28 days, the last treatment appointment of chemotherapy and/or radiotherapy NOTE: *Stage IIIA disease for thoracic cancer and excluded mesothelioma; if small cell lung cancer is present must be limited stage disease
• No more than 1 primary cancer
• No recurrent disease
• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Male or female
• Menopausal status not specified
• Able to speak/read English at an 8th grade level

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior brachytherapy only
• No prior surgery only (i.e., must have received prior adjuvant therapy and surgery)

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Fox Chase Cancer Center CCOP Research Base

Fox Chase Cancer Center – Philadelphia

Philadelphia Pennsylvania 19111-2497 United States

Overall Clinical Trial Officials and Contacts

Joanne Buzaglo, PhD Principal Investigator Fox Chase Cancer Center

Related Publications

References: Green BL, Krupnick JL, Rowland JH, Epstein SA, Stockton P, Spertus I, Stern N. Trauma history as a predictor of psychologic symptoms in women with breast cancer. J Clin Oncol. 2000 Mar;18(5):1084-93.

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00372840

Study ID Number: CDR0000464245

ClinicalTrials.gov Identifier: NCT00372840

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute’s PDQ® database

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

posted by Your Attorney at 3:17 PM
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Surgery Plus IPHC to Treat Peritoneal Carcinomatosis

Surgery Plus IPHC to Treat Peritoneal Carcinomatosis

Date First Received: March 29, 2007

Last Updated: April 2, 2007

Verified by: Wuhan University, April 2007

Clinical Trial Phase: Phase 2 | Start Date: March 2007

Overall Status: Recruiting

Estimated Enrollment: 60

Brief Summary

Official Title: “Cytoreductive Surgery Plus Intraoperative Peritoneal Hyperthermic Chemotherapy for the Treatment of Peritoneal Carcinomatosis From Gastrointestinal Cancer: an Open Label, Randomized, Prospective, Phase 2 Clinical Trial”

Condition Keyword(s):

• Stomach Neoplasms
• Colorectal Neoplasms
• Neoplasm Metastasis
• Mesothelioma

Intervention(s):

• Procedure: intraoperative peritoneal hyperthermic chemotherapy

OBJECTIVES:

• Determine response and survival of patients with peritoneal carcinomatosis treated with cytoreductive surgery plus intraoperative peritoneal hyperthermic chemotherapy with cisplatin and mitomycin
• Assess the quality of life of patients treated with this regimen.

OUTLINE: Patients are randomized into IPHC group and control group. In the former group, the patients undergo cytoreductive surgery plus intraoperative hyperthermic peritoneal perfusion with cisplatin and mitomycin over 60 minutes. Patients in the control group just underwent routine cytoreductive surgery.

All patients in both groups receive the standard conventional chemotherapy after surgery.

Quality of life is assessed at study initiation, at 1, 3, 6 months. Patients are followed at 4 weeks, every 3 months for 1 year, and then every 6 months for up to 3 years.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Detailed Clinical Trial Description

DISEASE CHARACTERISTICS: – Histologically confirmed peritoneal carcinomatosis with the following histologies: – Primary peritoneal mesothelioma – Adenocarcinoma of gastrointestinal tract origin – Confined to peritoneal cavity – Tumor mass could be debulked to less than 2.5 cm in diameter per tumor deposit – Must not have failed prior intraperitoneal platinum therapy – Treatment failure is defined as radiographic evidence of disease progression on 2 consecutive CT scans within 3 months after therapy

PATIENT CHARACTERISTICS:

• Age: - 20 to 70 years old
• Performance status: – KPS>50
• Life expectancy: – More than 8 weeks
• Hematopoietic: - WBC at least 3,500/mm^3 – Platelet count at least 80,000/mm^3
• Hepatic: – Bilirubin no greater than 2 times upper limit of normal (ULN) – AST and ALT no greater than 2 times ULN – Liver enzymes no greater than 2 times ULN
• Renal: – Creatinine no greater than 1.5 mg/dL
• Cardiovascular: – No significant irreversible cardiac ischemia – No significant changes in ECG recording
• Pulmonary: – FEV_1 at least 1.2 liters – Maximum voluntary ventilation at least 50% expected
• Other: – Not pregnant or nursing – Negative pregnancy test – No concurrent medical problems that would preclude surgery

Outcome Measures for this Clinical Trial

Primary:

• survival time
• time to treatment failure

Secondary:

• perioperative morbidity and mortality

Criteria for Participation in this Clinical Trial

Inclusion Criteria:

• Gastric cancer or colorectal cancer with peritoneal carcinomatosis
• Gastric cancer or colorectal cancer with malignant ascites
• Karnofsky Performance Scale(KPS)>50

Exclusion Criteria:

• Age less than 20 years old, or beyond 70 years old
• Any lung metastasis, liver metastasis, or prominent retroperitoneal lymph node metastasis
• Bilirubin greater than 3 times upper limit of normal (ULN)
• AST and ALT greater than 5 times ULN
• Liver enzymes greater than 3 times ULN

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Wuhan University

Cancer Center of Wuhan University & Department of Oncology, Zhongnan Hospital of Wuhan University

Wuhan Hubei 430071 China

Overall Clinical Trial Officials and Contacts

Yan Li, M.D., Ph.D Principal Investigator Cancer Center of Wuhan University

Overall Contact: Yan Li, M.D., Ph.D +86-27-62337478 liyansd2@163.com

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00454519

Study ID Number: WUCC-0701

ClinicalTrials.gov Identifier: NCT00454519

Health Authority: China: Ministry of Health

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

posted by Your Attorney at 3:14 PM
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A Study To Find the Best Dose of SU011248 When Given With Pemetrexed, Pemetrexed and Cisplatin Or Pemetrexed and Carboplatin in Patients With Advanced

Date First Received: September 10, 2007
Last Updated: April 9, 2008
Verified by: Pfizer, April 2008
Clinical Trial Phase: Phase 1 Start Date: November 2006
Overall Status: Recruiting
Estimated Enrollment: 100

Rationale

Intervention(s): Drug: Sunitinib, Pemetrexed, Cisplatin, Carboplatin

This study will assess the maximum tolerated dose, overall safety and antitumor activity of SU011248 in combination with pemetrexed, pemetrexed and cisplatin or pemetrexed and carboplatin in patients with advanced solid tumors.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study

Outcome Measures for this Clinical Trial

Primary
• To determine maximally tolerated dose of SU011248 (dosed continuously or on a 2/1 Schedule) when given in combination with pemetrexed, pemetrexed and cisplatin or pemetrexed and carboplatin. From screening until at least 28 days beyond discontinuation of study treatment

Secondary
• To evaluate the pharmacokinetics of SU011248 and pemetrexed, SU011248, pemetrexed and cisplatin and SU011248, pemetrexed and carboplatin when these drugs are co-administered. From screening until disease progression or discontinuation of the study
• To preliminarily assess the antitumor activity of SU011248 and pemetrexed in non-small cell lung cancer patients. From screening until disease progression or discontinuation of the study
• To preliminarily assess the antitumor activity of SU011248, pemetrexed and cisplatin and SU011248, pemetrexed and carboplatin in patients with non-small cell lung cancer or advanced unresectable mesothelioma. From screening until disease progression or discontinuation of the study

Inclusion Criteria

• Patients with a diagnosis of a solid cancer which is not responsive to standard therapy or for which no standard therapy exists.

• Patient has a good performance status (ECOG 0 or 1).

Exclusion Criteria

• Prior treatment with either pemetrexed or SU011248.

• Coughing up blood within 4 weeks before starting study treatment (small amounts okay).

• Hypertension that cannot be controlled by medications.

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Pfizer

Overall Clinical Trial Officials and Contacts: Pfizer CT.gov Call Center Study Director Pfizer

Overall Contact: Pfizer Oncology Clinical Trial Information Service 1-877-369-9753 PfizerCancerTrials@emergingmed.com

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00528619
Study ID Number: A6181084
ClinicalTrials.gov Identifier: NCT00528619

Labels: ClinicalTrial

posted by Your Attorney at 3:11 PM
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Gene Therapy for Pleural Malignancies

Date First Received: March 3, 2006
Last Updated: March 3, 2006
Clinical Trial Phase: Phase 1 Start Date: March 2006
Overall Status: Recruiting
Estimated Enrollment: 15

Intervention(s): Gene Transfer: BG00001 (adenoviral-mediated interferon-beta)

Condition Keyword(s):
• Pleural Mesothelioma
• Metastatic Pleural Effusions

Rationale

This Phase I study will evaluate the safety of two doses of BG00001. Eligible subjects will have: – malignant pleural mesothelioma, or – pleural effusions who have progressed through at least one prior therapy or have refused therapy
BG00001 is given twice, on Day 1 and Day 15. BG00001 is given through a catheter in the pleural space.

Ad.hIFN-β (BG00001) is a replication-defective recombinant adenoviral vector containing the human interferon-beta (hIFN-β) gene. This Phase I study is designed to evaluate the safety and maximum tolerated dose (MTD) of two doses of intrapleural (IP) Ad.hIFN-β in subjects with pleural malignancies either metastatic or pleural mesothelioma.

Study Type: Interventional

Study Design: Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety Study

Outcome Measures for this Clinical Trial

Primary
• To determine the MTD/MED and toxicity of two doses of intrapleural BG00001 (Ad.hIFN-β).

• To analyze Ad.hIFN-β gene transfer with two doses (via pleural fluid ELISA for IFN-β).

Secondary
• To assess systemic and intrapleural cytokine responses as well as cellular and humoral immune responses after repeated BG00001 instillation.

• To assess, in a preliminary way, efficacy via tumor regression, time to progression and survival.

Inclusion Criteria

• pathologically documented malignant pleural effusion from malignant mesothelioma or, metastatic from primary lung, breast, gastrointestinal, genitourinary, melanoma, or sarcoma

• must have evaluable disease

• must have ECOG performance status of 0 or 1

• must have pleural space involved with tumor accessible for pleural catheter

• must have FEV1 > 1 liter or 40% of predicted value

• must have completed radiotherapy and/or treatment with chemotherapy, cytotoxic, or immunologic agents 4 weeks prior to dosing with BG00001

Exclusion Criteria

• malignant pleural effusions secondary to lymphoma

• rapidly re-accumulating, symptomatic malignant pleural effusions that require immediate mechanical or chemical pleurodesis for palliation

• presence of known untreated brain metastases

• use of concurrent systemic steroids or immunosuppressants

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: University of Pennsylvania
Hospital of the University of Pennsylvania
Philadelphia Pennsylvania 19104 United States

Overall Clinical Trial Officials and Contacts: Daniel H. Sterman, M.D. Principal Investigator University of Pennsylvania

Overall Contact: Adri Recio, RN 215-573-6760 arecio@mail.med.upenn.edu

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00299962
Study ID Number: 803776
ClinicalTrials.gov Identifier: NCT00299962

Labels: ClinicalTrial

posted by Your Attorney at 3:09 PM
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Fentanyl Sublingual Spray in Treating Patients With Breakthrough Cancer Pain

RATIONALE: Fentanyl sublingual spray may help relieve breakthrough pain in patients receiving opioids for cancer pain. PURPOSE: This randomized phase III trial is studying how well fentanyl sublingual spray works in treating breakthrough cancer pain…

Date First Received: October 1, 2007

Last Updated: April 1, 2008

Verified by: National Cancer Institute (NCI), March 2008
Clinical Trial Phase: Phase 3 Start Date: October 2007
Overall Status: Recruiting
Estimated Enrollment: 130
Brief Summary

Official Title: “A Randomized, Double-Blind, Placebo-Controlled Multi-Center Study to Evaluate the Safety and Efficacy of Fentanyl Sublingual Spray (Fentanyl SL Spray) for the Treatment of Breakthrough Cancer Pain”

Condition Keyword(s):

• Cancer

Intervention(s):

• Drug: fentanyl sublingual spray
• Procedure: pain therapy
• Procedure: questionnaire administration

RATIONALE: Fentanyl sublingual spray may help relieve breakthrough pain in patients receiving opioids for cancer pain.

PURPOSE: This randomized phase III trial is studying how well fentanyl sublingual spray works in treating breakthrough cancer pain.

Study Type: Interventional

Study Design: Supportive Care, Randomized, Double-Blind, Placebo Control

Detailed Clinical Trial Description

OBJECTIVES:

Primary – Determine the efficacy and safety of fentanyl sublingual (SL) spray for the treatment of breakthrough cancer pain in patients on around-the-clock opioids for their persistent cancer pain.

Secondary – Evaluate the safety of fentanyl SL spray in these opioid-tolerant patients. – Assess the patient’s satisfaction with treatment medication.

OUTLINE: This is a phase III, randomized, double-blind, placebo-controlled, multicenter study of the clinical response to fentanyl sublingual (SL) spray as a treatment for breakthrough cancer pain.

The study medication is administered under the tongue as a simple spray and can be self-administered by patients or assisted by their caregivers. In addition, there is a questionnaire assessing satisfaction with the treatment. Patients are titrated to an effective-dose of fentanyl SL spray in the open-label titration period and then proceed to the double-blind randomized period. Patients are treated for up to a total of 6-7 weeks (including both the open-label titration and the double-blind randomized periods).

Outcome Measures for this Clinical Trial

Primary:

• Pain relief by 30 minutes after dosing

Secondary:

• Pain relief at various time points
• Safety, tolerability, and acceptability

Criteria for Participation in this Clinical Trial

DISEASE CHARACTERISTICS:

• Diagnosis of cancer
• Opioid-tolerant, defined as undergoing opioid treatment for cancer-related pain for ≥ 7 days and meeting 1 of the following criteria:
• Receiving at least 60 mg of oral morphine/day
• Receiving at least 25 mcg of transdermal fentanyl/hour
• Receiving at least 30 mg of oxycodone/day
• Receiving at least 8 mg of oral hydromorphone/day
• Receiving an equianalgesic dose of another opioid
• Experiences persistent pain related to the cancer or its treatment of moderate or lesser intensity in the 24 hours prior to assessment by a verbal rating scale at the screening visit
• Experiences on average one to four breakthrough cancer pain episodes per day usually at least partially controlled by supplemental medication of at least 5 mg immediate-release morphine or an equivalent short-acting opioid (e.g., oxycodone, hydrocodone, or codeine with acetaminophen)
• Brain metastases allowed provided the patient has no signs or symptoms of increased intracranial pressure

PATIENT CHARACTERISTICS:

• Able to evaluate pain relief, assess medication performance, convey adverse events, and record each use of the study drug or supplemental medication in an electronic diary (a caregiver may provide the patient the medication and help with the electronic diary but cannot enter information)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No intolerable side effects to opioids or fentanyl
• No history of major organ system impairment or disease, that in the investigator’s or his/her designee’s opinion, could increase the risk associated with the use of opioids
• No uncontrolled hypertension (systolic blood pressure [BP] > 180 mm Hg or diastolic BP
• > 90 mm Hg on two occasions at least six hours apart) despite antihypertensive therapy
• No hypertensive crisis within the past two years
• No recent history (within the past two years) of transient ischemic attacks, neural vascular disease, stroke, or cerebral aneurysms
• No clinically uncontrolled sleep apnea
• No inability to assess pain or response to pain medications for any reason, including psychiatric disorder, concurrent medical disorder, or concomitant therapy
• No painful erythema, edema, or ulcers under the tongue

PRIOR CONCURRENT THERAPY:

• At least 30 days since prior investigational study product(s)
• At least 14 days since prior monoamine oxidase inhibitors
• Medications or therapies that have been and continue to be used for a chronic disease condition may be continued throughout the study provided the medication or therapy is stable in dose and frequency for at least one week prior to the screening visit
• Medications used to help manage pain (e.g., bisphosphonates, steroids, or gabapentin) allowed provided the medication is stable in dose and frequency for at least one week prior to the screening visit of the study and the dose/frequency are not anticipated to change during the study
• Short-acting commercially available fentanyl medications used to help manage breakthrough pain (e.g., buccal fentanyl [Fentora®] or transmucosal fentanyl [Actiq®]) allowed for up to one-week prior to study entry onto the open-label titration period, but are not allowed during the open-label titration period or double-blind randomization period of the study
• Patients who complete the double-blind period and final visit of this study are eligible to proceed to INSYS-INS-06-007

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Insys Therapeutics Inc

InSys Therapeutics, Incorporated

Phoenix Arizona 85044 United States

Overall Clinical Trial Officials and Contacts

Ellen Feigal, MD Study Chair Insys Therapeutics Inc

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008

Link to the current ClinicalTrials.gov record.
http://clinicaltrials.gov/show/NCT00538850

Study ID Number: CDR0000581128

ClinicalTrials.gov Identifier: NCT00538850

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute’s PDQ® database

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

posted by Your Attorney at 3:06 PM
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Study of Oral PXD101 in Patients With Advanced Solid Tumors or Lymphoma

Study of Oral PXD101 in Patients With Advanced Solid Tumors or Lymphoma

This is a Phase I dose escalation study of PXD101 administered orally. Oral belinostat will be given once or twice daily at various dosing schedules to patients with solid tumors. Doses will be escalated until the maximum tolerated dose (MTD) is identified. In parallel, a cohort of lymphoma patients will be given oral belinostat on a discontinuous once daily dosing schedule…

Date First Received: December 18, 2006

Last Updated: January 29, 2008

Verified by: CuraGen Corporation, January 2008

Clinical Trial Phase: Phase 1 Start Date: July 2006

Overall Status: Recruiting

Estimated Enrollment: 100

Brief Summary

Official Title: “Open Label, Dose Escalation Trial of Oral PXD101 in Patients With Advanced Solid Tumors”

Condition Keyword(s):
• Solid Tumor
• Lymphoma

Intervention(s):

• Drug: belinostat

This is a Phase I dose escalation study of PXD101 administered orally. Oral belinostat will be given once or twice daily at various dosing schedules to patients with solid tumors. Doses will be escalated until the maximum tolerated dose (MTD) is identified. In parallel, a cohort of lymphoma patients will be given oral belinostat on a discontinuous once daily dosing schedule.

Study Type: Interventional

Study Design: Treatment, Open Label, Single Group Assignment, Safety Study

Outcome Measures for this Clinical Trial

Primary:
• Safety, tolerability and maximum tolerated dose of orally administered PXD101 for each cohort throughout the study

Secondary:

• Determine the pharmacokinetics of oral PXD101 when dosed once or twice daily at various dose levels throughout the study
• Explore anti-tumor activity throughout the study
• Determine the safety, tolerability, and anti-tumor activity of orally administered PXD101 to patients with lymphoma throughout the trial

Criteria for Participation in this Clinical Trial

Inclusion Criteria:

• Age ≥ 18 years
• Solid tumor: Histologically confirmed solid tumors.
• Lymphoma: relapsed or refractory B-cell or T-cell lymphoma or Hodgkins disease
• At least one evaluable lesion. Lesions must be evaluated by computed tomography (CT), magnetic resonance imaging (MRI), or bone scan. Patients with prostate cancer, bone disease and rising prostate-specific antigen [PSA] but no other evaluable disease are eligible and will be evaluated based on PSA.
• Progressive disease: Progressive disease will be defined as new or progressive lesions on CT-scan, MRI, bone scan or by rising PSA
• ≥ 4 weeks since prior radiation therapy or chemotherapy
• Karnofsky performance ≥ 60%
• Acceptable liver, renal and bone marrow function to include:
• absolute neutrophil count ≥ 1.5 x 10^9/L
• hemoglobin ≥ 9.0 g/dl
• platelets ≥ 100 x 10^9/L
• bilirubin ≤ 1.5 x upper limit of normal (ULN)
• AST and ALT ≤ 3.0 x ULN (≤ 5.0 x ULN is acceptable if liver has tumor involvement)
• serum creatinine ≤ 1.5 x ULN
• PT-INR/PTT ≤ 1.5 x ULN, or for patients on anticoagulation therapy, status within therapeutic range
• Serum potassium within normal range
• Estimated life expectancy of greater than 3 months
• Signed informed consent prior to any study specific procedures

Exclusion Criteria:
• Prior treatment with PXD101
• Within 4 weeks of enrollment:
• major surgery
• metastatic disease requiring palliative treatment
• Anticancer therapy, including:
• chemotherapy
• radiotherapy
• endocrine therapy
• immunotherapy
• other investigational agents (6 weeks for mitomycin or nitrosourea)
• Serious concomitant systemic disorders (eg, active infection) compromising patient safety.
• Symptomatic brain metastases
• Significant cardiovascular disease, including:
• unstable angina pectoris
• uncontrolled hypertension
• congestive heart failure (New York Heart Association [NYHA] Class III or IV) related to primary cardiac disease, a condition requiring anti-arrhythmic therapy
• ischemic or severe valvular heart disease
• myocardial infarction within 6 months prior to the trial entry
• A marked baseline prolongation of QT/QTc interval, such as:
• repeated demonstration of a QTc interval > 500 msec
• Long QT syndrome
• required use of concomitant medication on dosing days that may cause torsade de pointes
• Altered mental status precluding understanding of the informed consent process and/or completion of the study
• Pregnant or breast-feeding women
• Refusal or inability to use effective means of contraception (for men and women of childbearing potential)
• History of, or test positive for, HIV.

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: CuraGen Corporation

Yale New Haven Hospital

New Haven Connecticut 06520 United States

Columbia University – Herbert Irving Cancer Center

New York New York 01132 United States

M.D. Anderson Cancer Center

Houston Texas 77230-1402 United States

Research Facility

Copenhagen Denmark

Research Facility

London Surrey SW3 6JJ United Kingdom

Overall Clinical Trial Officials and Contacts

Overall Contact: CuraGen Clinical Trial Call Center
877-462-4363
info@curagen.com

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00413075

Study ID Number: PXD101-CLN-9

ClinicalTrials.gov Identifier: NCT00413075

Health Authority: United States: Food and Drug Administration

Click here for more information about CuraGen’s Clinical Trials

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

posted by Your Attorney at 3:02 PM
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Electronic Tool to Record Cancer Symptoms in Patients With Advanced Cancer Receiving Palliative Care

RATIONALE: A hand held electronic tool used to monitor symptoms and assess quality of life may improve communication between patients and their doctors and improve the ability to plan treatment for patients with advanced cancer receiving palliative care. It is not yet known whether symptoms are better controlled with or without use of this electronic tool. PURPOSE: This randomized phase III trial…

Date First Received: May 23, 2007

Last Updated: December 25, 2007

Verified by: National Cancer Institute (NCI), October 2007

Clinical Trial Phase: Phase 3 Start Date: February 2007

Overall Status: Recruiting

Estimated Enrollment: 192

Brief Summary

Official Title: “E-MOSAIC: A Multicenter Randomized Controlled Phase III Study of Longitudinal Electronic Monitoring of Symptoms and Syndromes Associated With Advanced Cancer in Patients Receiving Anticancer Treatment in Palliative Intention”

Condition Keyword(s):

• Cancer

Intervention(s):

• Procedure: cognitive assessment
• Procedure: counseling
• Procedure: fatigue assessment and management
• Procedure: psychosocial assessment and care
• Procedure: quality-of-life assessment

RATIONALE: A hand held electronic tool used to monitor symptoms and assess quality of life may improve communication between patients and their doctors and improve the ability to plan treatment for patients with advanced cancer receiving palliative care. It is not yet known whether symptoms are better controlled with or without use of this electronic tool.

PURPOSE: This randomized phase III trial is studying an electronic tool to see how well it records cancer symptoms in patients with advanced cancer receiving palliative care.

Study Type: Interventional

Study Design: Health Services Research, Randomized, Active Control

Detailed Clinical Trial Description

OBJECTIVES:

Primary – Determine the effect of an electronic tool for monitoring symptoms and syndromes associated with advanced cancer (E-MOSAIC) and a Longitudinal Monitoring Sheet (LoMoS) on global quality of life (G-QOL) of patients with advanced incurable cancer receiving palliative anticancer treatment.

Secondary – Determine if this tool affects communication between these patients and their treating physicians. – Determine if this tool affects the symptoms and syndromes reported by these patients. – Determine if this tool impacts symptom management performance.

Tertiary – Identify factors influencing changes in G-QOL. – Determine how patients adapt to illness and burden of treatment. – Describe patients’ decision-making preference.

OUTLINE: This is a controlled, randomized, longitudinal, multicenter study. Physicians are stratified according to participating center. Physicians are randomized to 1 of 2 arms. All patients allocated to a physician undergo the same intervention. – Arm I: Patients complete a weekly symptom assessment and nutritional intake using a Palm-based monitoring tool. Nurses record weight and Karnofsky performance status (KPS) scores weekly. A proof of electronic transfer sheet is printed and stored. – Arm II: Patients complete a weekly assessment comprising visual analogue scales (VAS) of pain, fatigue, drowsiness, nausea, anxiety, depression, shortness of breath, loss of appetite, and overall well-being; up to 3 optional symptoms selected by the patient; and an estimated nutritional intake using an electronic tool for monitoring symptoms and syndromes associated with advanced cancer (E-MOSAIC). Nurses record the patient’s weight, KPS score, body mass index, and assessment of current medication for pain (i.e., morphine-equivalent daily dose), fatigue, and anorexia/cachexia syndromes weekly. A Longitudinal Monitoring Sheet (LoMoS) is printed (comprising VAS of pain, pain medication, fatigue, KPS, medication for fatigue [i.e., methylphenidate hydrochloride or epoetin alfa], anorexia, weight change, nutritional intake, medication, supplements, counseling for anorexia, VAS of individually selected symptoms) and stored.

In both arms, patients are assessed for outcome criteria at baseline and at weeks 3 and 6 (end of study).

PROJECTED ACCRUAL: A total of 24 physicians and 192 patients will be accrued for this study.

Outcome Measures for this Clinical Trial

Primary:

• Change in global quality of life (G-QOL) as measured at baseline and after study completion

Secondary:

• G-QOL after study completion
• Communication as measured by patients’ estimation of physicians’ compassion and attribute and physicians’ satisfaction with patient-physician communication
• Change in symptoms and syndromes as measured by difference in Edmonton Symptom Assessment Scale Score, Karnofsky performance status, weight, shortness of breath, nutritional intake, and 3 patient chosen symptoms at baseline and after study completion
• Symptom management performance as measured by number of visits with a symptom load above a defined threshold of 5 symptoms without immediate intervention and number of accompanying persons in weeks 3-6
• Factors influencing the change in G-QOL (i.e., tumor response [complete and partial response, stable or progressive disease], tumor type, predominant symptom, anxiety, complexity, education, hospitalization)
• Change in burden of illness and treatment over time
• Comparison of the number of mismatched decision-making preferences between weeks 3-6

Criteria for Participation in this Clinical Trial

DISEASE CHARACTERISTICS:

• Diagnosis of advanced incurable cancer
• Symptomatic disease, defined as meeting ≥ 1 of the following criteria:
• Pain Visual Analogue Scale (VAS) ≥ 3/10 and/or morphine equivalent daily dose of ≥ 10 mg for ≥ 3 days
• Anorexia VAS ≥ 3/10 and/or weight loss of ≥ 2% in 2 months or ≥ 5% in 6 months
• Fatigue VAS ≥ 3/10 and/or Karnofsky performance status greater than 70%
• Depression or anxiety VAS ≥ 3/10 and/or treatment with antidepressants for ≥ 5 days and planned for ≥ 1 month
• Receiving continuously, weekly, or biweekly palliative anticancer treatment meeting 1 of the following criteria:
• At least 1 first-line treatment for any of the following:
• Metastatic melanoma
• Renal cell cancer
• Pancreatic cancer
• Biliary tract cancer
• Mesothelioma
• Prostate cancer (chemotherapy)
• Advanced glioblastoma
• At least 1 second-line treatment for any of the following:
• Extensive stage small cell lung cancer
• Stage IV non-small cell lung cancer
• Colorectal cancer
• Gastric cancer
• Esophageal cancer
• Bladder cancer
• Sarcoma
• Carcinoma of unknown primary
• At least 1 third-line chemotherapy regimen for any of the following:
• Metastatic breast cancer
• Ovarian cancer
• Anticancer treatment must be given in an outpatient setting, not within a clinical trial, with weekly monitoring, and expected tumor response rate ≤ 20% according to the literature
• No testicular cancer
• No hematological malignancies
• No primary brain tumors other than glioblastoma
• Physician characteristics:
• No change to standard of care for symptom assessment or to major communication skills strategies within the past 3 months
• Experienced in medical oncology (i.e., worked ≥ 50% in clinical oncology within the past 24 months)
• Likely to stay in the participating institution for the time required to treat ≥ 5 study patients
• Able to independently communicate with the patient about all aspects of cancer care
• Able to independently perform immediate changes of interventions in patient care without the institutional requirement to counsel another colleague before prescribing (i.e., for symptom control)
• Completed a basic communication skills course or equivalent training (i.e., familiar with communication skills)

PATIENT CHARACTERISTICS:

• Able to understand assessment instrument language
• Able to understand physician communication without difficulty (i.e., due to culture, language, speech)

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No concurrent participation in another clinical trial

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Swiss Group for Clinical Cancer Research

Kantonsspital – St. Gallen

St. Gallen CH-9007 Switzerland

Overall Clinical Trial Officials and Contacts

Florian Strasser, MD Study Chair Kantonsspital – St. Gallen

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00477919

Study ID Number: CDR0000536483

ClinicalTrials.gov Identifier: NCT00477919

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute’s PDQ® database

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

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Rapamycin With Grapefruit Juice for Advanced Malignancies

The purpose of this study is to determine the highest safe dose of rapamycin when given with a fixed amount of grapefruit juice…

Date First Received: September 11, 2006

Last Updated: April 24, 2008

Verified by: University of Chicago, April 2008

Clinical Trial Phase: Phase 1 Start Date: September 2006

Overall Status: Recruiting

Estimated Enrollment: 64

Brief Summary

Official Title: “A Phase Ib Study Administering Rapamycin (Sirolimus) With Grapefruit Juice in Patients With Advanced Malignancies”

Condition Keyword(s):

• Tumors
• Neoplasm Metastasis

Intervention(s):

• Drug: Rapamycin (sirolimus)
• Other: Grapefruit Juice

The purpose of this study is to determine the highest safe dose of rapamycin when given with a fixed amount of grapefruit juice.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety Study

Outcome Measures for this Clinical Trial

Primary:

• Pharmacokinetic interaction 4 weeks

Criteria for Participation in this Clinical Trial

Inclusion Criteria:

• Histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
• Patients with hematologic malignancies (lymphoma, multiple myeloma and chronic lymphocytic leukemia (CLL) only) are eligible to participate in the phase IB portion of the trial only.
• At least 4 weeks since prior chemotherapy or radiation therapy
• Aged 18 years or older
• ECOG performance status 0-2
• Life expectancy of greater than 3 months.
• Normal organ and marrow function:
• No transfusions of packed red blood cells within 1 week of starting treatment
• Leukocytes greater or equal to 3,000/µL
• ** White blood cell (WBC) greater or equal to 1,500/µL for patients with hematologic malignancies
• Absolute neutrophil count (ANC) greater or equal to 1,500/µL
• ** ANC greater or equal to 1,000/µL for patients with hematologic malignancies
• Platelets (PLT) greater or equal to 100,000/µL
• ** PLT greater or equal to 50,000/µL for patients with hematologic malignancies
• Total bilirubin within normal institutional limits
• AST (SGOT) and ALT (SGPT) less than or equal to 2.5 times institutional upper limit of normal
• Serum triglycerides less than or equal to 500 mg/dl
• Creatinine within normal institutional limits OR creatinine clearance greater or equal to 60 mL/min for patients with creatinine levels above institutional normal
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence)
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• May not be receiving any other investigational agents.
• Uncontrolled brain metastases or malignancy. Cannot be receiving enzyme-inducing anticonvulsants.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to rapamycin
• Gastrointestinal malabsorption syndromes, partial small bowel obstruction, or any illness that would interfere with the ability to absorb oral medications.
• Uncontrolled intercurrent illness
• Severe immunodeficient states (as judged by the treating physician)
• Pregnant women are excluded from this study; breastfeeding should be discontinued.
• HIV-positive patients receiving combination antiretroviral therapy are excluded.
• Concurrent use of ketoconazole, cyclosporine, tacrolimus, diltiazem, and rifampin with rapamycin is not permissible. The concurrent use of calcium channel blockers, terfenadine, astemizole, cisapride, propafenone, cyclosporine, midazolam, triazolam, quinidine, or theophylline with grapefruit juice is not permissible.

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: University of Chicago

University of Chicago Hospitals

Chicago Illinois 60637 United States

Overall Clinical Trial Officials and Contacts

Ezra W Cohen, MD Principal Investigator University of Chicago

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00375245

Study ID Number: 14435B

ClinicalTrials.gov Identifier: NCT00375245

Health Authority: United States: Institutional Review Board

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

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Phase I Study of OSI-930 and Erlotinib in Cancer Tumors

This is a Phase I, dose escalation, safety study of OSI-930 and Erlotinib in cancer tumors.

Date First Received: December 26, 2007

Last Updated: April 15, 2008

Verified by: OSI Pharmaceuticals, April 2008

Clinical Trial Phase: Phase 1 Start Date: November 2007

Overall Status: Recruiting

Estimated Enrollment: 60

Brief Summary

Official Title: “A Phase 1 Dose Escalation Study of Daily Oral OSI-930 and Erlotinib (Tarceva) in Patients With Advanced Solid Tumors”

Condition Keyword(s):
• Advanced Solid Tumors

Intervention(s):

• Drug: OSI-930 and erlotinib

This is a Phase I, dose escalation, safety study of OSI-930 and Erlotinib in cancer tumors.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety Study

Detailed Clinical Trial Description

Multicenter, open-label, phase 1, dose escalation study to determine the maximum tolerated dose of OSI-930 and Erlotinib.

Patients may continue to receive OSI-930 and Erlotinib until one of the following occurs:

disease progression, adverse event requiring withdrawal, failure to recover from toxicity despite a 14-day dosing interruption, medical or ethical reasons, patient request, or patient death.

Outcome Measures for this Clinical Trial

Primary:
• Determine the maximum tolerated dose (MTD), evaluate the pharmacokinetic profiles 18 months

Secondary:

• Safety, evaluate pharmacodynamic relationships 18 months

Criteria for Participation in this Clinical Trial

Inclusion Criteria:
• Histology or cytologically documented malignancy that is now advanced and/or metastatic and refractory to established forms of therapy or for which no effective therapy exists
• Age greater than or equal to 18 years
• ECOG PS 0-2
• ANC greater than or equal to 1.5 x 10^9/L
• Bilirubin less than or equal to 1.5 x upper limit of normal (ULN), AST and ALT less than or equal to 2.5 x ULN
• Creatinine less than or equal to 1.5 ULN
• Predicted life expectancy greater than or equal to 12 weeks
• Prior chemotherapy is permitted provided that a minimum of 3 weeks has elapsed
• Prior tyrosine kinase inhibitor therapy is permitted
• Patients must have recovered from any treatment-related toxicities (with some exceptions) prior to registration
• Prior hormonal therapy is permitted provided it is discontinued prior to registration (with the exception of prostate cancer patients who have been on hormone therapy for at least 3 months)
• Prior radiation therapy is permitted provided that it did not exceed 25% of bone marrow reserve and patients have recovered from the toxic effects (a minimum of 21 days must have elapsed unless the radiotherapy was palliative and nonmyelosuppressive)
• Prior surgery is permitted, provided that wound healing has occurred prior to registration
• Patients must use proactive effective contraceptive measures throughout the study
• Provide written informed consent
• Accessible for repeat dosing and follow-up
• Adequate hematopoietic, hepatic, and renal function

Exclusion Criteria:

• Significant cardiac disease unless well controlled
• Current or former smokers, unless patients stopped smoking greater than 3 months prior to registration
• Active or uncontrolled infections of serious illnesses or medical conditions that could interfere with participation
• History of unacceptable toxicity with previous ECFR inhibitor therapy
• History of any psychiatric condition that might impair the patient’s ability to provide informed consent or participate
• Use of CYP3A4 inducers/inhibitors during the 14 days prior to first dose
• Pregnant or breast-feeding females
• Symptomatic brain metastases which are not stable, require steroids, are potentially life-threatening or that have required radiation within the last 28 days
• History of allergic reaction attributed to a similar compound as study drug
• GI abnormalities including ability to take oral medications, required for IV alimentation
• Clinically significant ophthalmologic abnormalities

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: OSI Pharmaceuticals

H Lee Moffitt Cancer Center and Research Institute

Tampa Florida 33612 United States

The Beatson West of Scotland Cancer Centre

Glasgow G12 0YN United Kingdom

Overall Clinical Trial Officials and Contacts

Overall Contact: OSIP Medical Informaiton 800.572.1932, x7821 medical-information@osip.com

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00603356

Study ID Number: OSI-930-103

ClinicalTrials.gov Identifier: NCT00603356

Health Authority: United States: Food and Drug Administration

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

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An Analysis of the Response of Human Tumor Microvascular Endothelium to Ionizing Radiation

Doctors will take some tissue from the tissue removed during surgery in order to study how the blood vessels of the tumor respond to radiation therapy. The tissue obtained will be used to determine how these tumor blood vessels respond to radiation therapy delivered to the tumor, after it has been removed. This radiation is delivered in the research lab.

Date First Received: August 18, 2005

Last Updated: November 29, 2007

Verified by: Memorial Sloan-Kettering Cancer Center, November 2007

Clinical Trial Phase: Phase 3 Start Date: August 2004

Overall Status: Recruiting

Estimated Enrollment: 150

Brief Summary

Official Title: “An Analysis of the Response of Human Tumor Microvascular Endothelium to Ionizing Radiation”

Condition Keyword(s):

• Ovarian Neoplasms
• Colorectal Neoplasms
• Melanoma
• Small Cell Lung Cancer
• Liposarcoma

Intervention(s):

• Radiation: Ionizing radiation (IR) therapy
• Radiation: Ionizing radiation (IR)

Doctors will take some tissue from the tissue removed during surgery in order to study how the blood vessels of the tumor respond to radiation therapy. The tissue obtained will be used to determine how these tumor blood vessels respond to radiation therapy delivered to the tumor, after it has been removed. This radiation is delivered in the research lab. This research is being conducted in order to develop new methods to treat tumors by radiation therapy. No additional surgery will be performed to obtain these samples, and only materials that remain after all diagnostic testing has been completed will be used.

Study Type: Observational

Study Design: Cohort, Prospective

Detailed Clinical Trial Description

The goal of this study is to determine if concepts established in mouse models of the tumor microvascular response to ionizing radiation (IR) therapy are applicable to human tumors in order to begin to establish that the engagement of the endothelial response is a valid target for IR in human tumors. A portion of tumor will be isolated from individuals who have signed informed consent for this protocol and are undergoing surgery on the Neurosurgery, Colorectal, and Gynecology, Head and Neck, Urology, and Hepatobiliary Services at Memorial Sloan-Kettering Cancer Center. Tumor tissue will be obtained from the surgical sample in pathology after adequate specimens have been obtained for diagnostic purposes. Tumor tissue will be irradiated ex vivo and the microvascular endothelial response will be determined.

From specimens of adequate size, a pure tumor endothelial cell population will be isolated and the response to IR will be determined.

Primary Outcomes: – To determine if human tumor microvascular endothelium displays similar dose parameters as mouse tumor endothelium.

Secondary Outcomes: – To determine if tumor endothelium isolated to near homogeneity demonstrates dose parameters similar to those used in single dose radiotherapy of brain tumors. – To determine if the microvascular endothelium of tumors of different types behaves in a similar fashion in its response to IR.

Criteria for Participation in this Clinical Trial

Inclusion Criteria:

• Patients who are felt to have adequate tumor volume for these studies, at least a 2 x 2 x 2 cm3 tumor by physical exam, imaging studies or colonoscopy reports
• Primary or recurrent tumors are eligible
• Patients must be suitable candidates for surgery
• Patients who have signed the informed consent

Exclusion Criteria:

• Patients who are not considered suitable candidates for surgery
• Patients who have received prior radiation therapy to the tumor being removed
• Patients who have received chemotherapy within 6 months of tumor removal
• Patients who are pregnant
• Patients may choose to be excluded at any time
• Minors are excluded from this study because there are expected to be very few minors with the tumor types which the investigators are evaluating in this study

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Memorial Sloan-Kettering Cancer Center

Memorial Sloan-Kettering Cancer Center

New York New York 10021 United States

Overall Clinical Trial Officials and Contacts

Michael Zelefsky, M.D. Principal Investigator Memorial Sloan-Kettering Cancer Center
Overall Contact: Michael Zelefsky, M.D. 212-639-6802
zelefskm@mskcc.org

Additional Information
Information obtained from ClinicalTrials.gov on April 29, 2008

Link to the current ClinicalTrials.gov record.
http://clinicaltrials.gov/show/NCT00132704
Study ID Number: 04-109

ClinicalTrials.gov Identifier: NCT00132704

Health Authority: United States: Institutional Review Board
(Memorial Sloan-Kettering Cancer Center)
Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

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Study of Carboplatin and Vinorelbine in Malignant Pleural Mesothelioma

The purpose is to evaluate the activity and feasibility of a two drug regimen which is partly orally and partly intraveneous in advanced pleural mesothelioma…

Date First Received: January 3, 2006

Last Updated: September 8, 2006

Verified by: Rigshospitalet, Denmark, September 2006

Clinical Trial Phase: Phase 2 Start Date: September 2004

Overall Status: Recruiting

Estimated Enrollment: 40
Brief Summary

Official Title: “Phase II Study of Carboplatin and Vinorelbine i.v. (Day 1) and Orally (Day for Malignant Pleural Mesothelioma.”

Condition Keyword(s):

• Malignant Pleural Mesothelioma

Intervention(s):

• Drug: Carboplatin and Vinorelbine

The purpose is to evaluate the activity and feasibility of a two drug regimen which is partly orally and partly intraveneous in advanced pleural mesothelioma.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Efficacy StudyDetailed

Clinical Trial Description

Chemotherapy with carboplatin i.v. day one in each cycle Vinorelbine i.v. day one, and orally day 8 in each cycle, repeat new cycle every 3 weeks. Total of 6 cycles.

Endpoint is response rate, secondary endpoints survival and toxicity.Outcome Measures for this Clinical Trial

Primary:

• Response

Secondary:

• Survival
• Feasibility

Criteria for Participation in this Clinical Trial

Inclusion Criteria:

• Histologically verified malignant pleural Mesothelioma
• Age above 18 years
• Performance status 0-2

Exclusion Criteria:

• No previous chemotherapy
• Normal renal, liver and bone marrow function

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Rigshospitalet, Denmark

Dept. Oncol., Rigshospitalet

Copenhagen 2100 Denmark

Overall Clinical Trial Officials and Contacts

Jens B Sorensen, MD Study Chair Dept. Oncology, Rigshospitalet

Overall Contact: Jens B. Sorensen, MD 35454392 jbsonk@rh.dk

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00272558

Study ID Number: MPM phase II Carbo/VNB

ClinicalTrials.gov Identifier: NCT00272558

Health Authority: Denmark: National Board of HealthClinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

posted by Your Attorney at 2:33 PM
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Combination Chemotherapy With or Without Surgery and Radiation Therapy in Treating Patients With Mesothelioma That Can Be Removed By Surgery

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy before surgery may shrink the tumor so that it can be removed…

Date First Received: November 11, 2005
Last Updated: April 8, 2008
Verified by: National Cancer Institute (NCI), March 2008
Clinical Trial Phase: N/A
Start Date: May 2005
Overall Status: Recruiting
Estimated Enrollment: 670

Brief Summary Official Title: “Mesothelioma and Radical Surgery Trial”

Condition Keyword(s):

• Malignant Mesothelioma

Intervention(s):

• Procedure: adjuvant therapy
• Procedure: chemotherapy
• Procedure: conventional surgery
• Procedure: neoadjuvant therapy
• Procedure: radiation therapy

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy before surgery may shrink the tumor so that it can be removed. Giving radiation therapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether combination chemotherapy is more effective with or without surgery and radiation therapy in treating mesothelioma.

PURPOSE: This randomized clinical trial is studying combination chemotherapy, surgery, and radiation therapy to see how well they work compared to combination chemotherapy alone in treating patients with mesothelioma that can be removed by surgery.

Study Type: Interventional

Study Design: Treatment, Randomized, Active Control Detailed Clinical Trial Description

OBJECTIVES: – Compare the feasibility of neoadjuvant combination chemotherapy with vs without surgery and adjuvant radiotherapy in patients with resectable malignant mesothelioma. – Compare the overall survival of patients treated with these regimens. – Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a multicenter, pilot study followed by a randomized, controlled study.

Patients undergo 3 courses of a platinum-based (cisplatin or carboplatin) combination chemotherapy regimen to be determined by the treatment center. Upon completion of combination chemotherapy, patients are randomized to 1 of 2 treatment arms provided tumor is resectable and there is no disease progression. – Arm I: Patients undergo extra-pleural pneumonectomy followed by post-operative radiotherapy. – Arm II: Patients undergo follow-up only. Patients may receive additional standard therapy according to their treatment center.

Quality of life is assessed at baseline, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

After completion of study treatment, patients are followed periodically for 2 years and then annually thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK PROJECTED ACCRUAL: A total of 50-670 patients will be accrued for this study.

Criteria for Participation in this Clinical Trial

DISEASE CHARACTERISTICS:

• Histologically and immuno-histochemically confirmed malignant mesothelioma
• Resectable disease (T1-3, N0-1, M0) with no distant metastases
• Eligible to undergo extra-pleural pneumonectomy based on British Thoracic Society guidelines

PATIENT CHARACTERISTICS:

• Performance status
• WHO 0-1
• Life expectancy
• Not specified
• Hematopoietic
• Not specified
• Hepatic
• Not specified
• Renal
• Normal renal function
• Cardiovascular
• Ejection fraction ≥ 40%
• Pulmonary
• Predicted post-operative FEV_1 ≥ 40%
• Predicted post-operative DLCO ≥ 40%
• No significant pulmonary hypertension
• Other
• No physical or personal condition that would preclude ability to undergo chemotherapy or post-operative radiotherapy
• No physical or personal condition that would preclude ability to comply with follow-up requirements

PRIOR CONCURRENT THERAPY:

• Not specified

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Institute of Cancer Research, United Kingdom
Addenbrooke’s Hospital Cambridge England CB2 2QQ United Kingdom
Berkshire Cancer Centre at Royal Berkshire Hospital Reading England RG1 5AN United Kingdom
Birmingham Heartlands Hospital Birmingham England B9 5SS United Kingdom
Bristol Royal Infirmary Bristol England BS2 8HW United Kingdom
Cancer Research Centre at Weston Park Hospital Sheffield England S1O 2SJ United Kingdom
Cookridge Hospital Leeds England LS16 6QB United Kingdom
Glenfield Hospital Leicester England LE3 9QP United Kingdom
Institute of Cancer Research – Sutton Sutton England SM2 5NG United Kingdom
Ipswich Hospital Ipswich England IP4 5PD United Kingdom
Leicester Royal Infirmary Leicester England LE1 5WW United Kingdom
Nottingham City Hospital NHS Trust Nottingham England NG5 1PB United Kingdom
Papworth Hospital Cambridge England CB3 8RE United Kingdom
Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust Birmingham England B15 2TH United Kingdom
Queen’s Hospital Burton-upon-Trent England DE13 0RB United Kingdom
Royal Marsden – London London England SW3 6JJ United Kingdom
Royal Marsden – Surrey Sutton England SM2 5PT United Kingdom
St. Thomas’ Hospital London England SE1 9RT United Kingdom

Overall Clinical Trial Officials and Contacts Clare Peckitt Study Chair Institute of Cancer Research, United Kingdom

Additional Information Information obtained from ClinicalTrials.gov on April 29, 2008 Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00253409

Study ID Number: CDR0000448615

ClinicalTrials.gov Identifier: NCT00253409

Health Authority: Unspecified Clinical trial summary from the National Cancer Institute’s PDQ® database

Clinical Trials Authorship and Review Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org.

Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

posted by Your Attorney at 2:18 PM
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Dendritic Cell-Based Immunotherapy in Mesothelioma

Exploiting the immunostimulatory capacities of dendritic cells holds great promise for cancer immunotherapy. A mouse model for malignant mesothelioma allowed us to prove that autologous dendritic cells presenting tumor antigens were very effective by (partly) inhibiting tumor growth. This study will test the feasibility and safety of a clinical trial using autologous DC as a therapeutic adjuvant.

Date First Received: January 20, 2006

Last Updated: April 10, 2007

Verified by: Erasmus Medical Center, April 2007

Clinical Trial Phase: Phase 1 Start Date: January 2006

Overall Status: Recruiting

Estimated Enrollment: 10

Brief Summary Official Title: “Vaccination With Autologous Dendritic Cells Pulsed With Tumor Lysate for Treatment of Patients With Malignant Pleural Mesothelioma”

Condition Keyword(s):

• Malignant Pleural Mesothelioma

Intervention(s):

• Biological: tumor lysate-loaded autologous dendritic cells

Exploiting the immunostimulatory capacities of dendritic cells holds great promise for cancer immunotherapy. A mouse model for malignant mesothelioma allowed us to prove that autologous dendritic cells presenting tumor antigens were very effective by (partly) inhibiting tumor growth. This study will test the feasibility and safety of a clinical trial using autologous DC as a therapeutic adjuvant for the treatment of malignant pleural mesothelioma.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study

Detailed Clinical Trial Description

For this phase I study, patients with end-stage malignant mesothelioma and who are deemed to be fit enough to be treated with chemotherapy will be asked to participate in this study.

Patients will first be treated with 4 courses of chemotherapy (standard treatment[Alimta/cisplatin]). After this chemotherapy a leukapherese is performed of which the monocytes are used for differentiation to dendritic cells. The procedure to grow these dendritic cells in vitro (culture) and pulse them with tumor lysate is performed in a cleanroom environment. Several quality control tests will be performed before the dendritic cells are ready for re-injection. Three doses of properly pulsed autologous dendritic cells are then re-injected every two weeks.

Using the proper procedure in mesothelioma patients, minor side effects are expected.

Ten (10) patients will be treated by this procedure to define the safety and toxicity of immunization and to observe (anti-tumor) immune responses.

Outcome Measures for this Clinical Trial

Primary:

• safety
• tolerability

Secondary:

• anti-tumor responses in vitro and in vivo
• clinical response evaluation Criteria for Participation in this Clinical Trial

Inclusion Criteria:

• Patients with clinically and histological or cytological confirmed newly diagnosed mesothelioma, that can be measured in two dimensions by a radiologic imaging study.
• Patients must be at least 18 years old and must be able to give written informed consent.
• Patients must be ambulatory (Karnofsky scale > 70, or WHO-ECOG performance status 0,1, or 2) and in stable medical condition. The expected survival must be at least 4 months.
• Patients must have normal organ function and adequate bone marrow reserve: absolute neutrophil count > 1.5*109/l, platelet count > 100*109/l, and Hb > 6.0 mmol/l.
• Positive delayed type hypersensitivity skin test (induration > 2mm after 48hrs) against at least one positive control antigen of MULTITEST CMI (Pasteur merieux).
• Stable disease or response after chemotherapy. • Availability of sufficient tumor material of the patient.
• Ability to return to the Erasmus MC for adequate follow-up as required by this protocol.

Exclusion Criteria:

• Conditions that make the patient unfit for chemotherapy or progressive disease after 4 cycles of chemotherapy.
• Pleurodesis at the affected side before the pleural fluid is obtained.
• Medical or psychological impediment to probable compliance with the protocol.
• Patients on steroid (or other immunosuppressive agents) are excluded on the basis of potential immune suppression. Patients must have had 6 weeks of discontinuation and must stop of any such treatment during the time of the study.
• No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, superficial or in-situ cancer of the bladder or other cancer for which the patient has been disease-free for five years.
• Serious concomitant disease, no active infections. Patients with a history of autoimmune disease or organ allografts, or with active acute or chronic infection, including HIV and viral hepatitis.
• Patients with serious intercurrent chronic or acute illness such as pulmonary (asthma or COPD) or cardiac (NYHA class III or IV) or hepatic disease or other illness considered by the study coordinators to constitute an unwarranted high risk for investigational DC treatment.
• Patients with a known allergy to shell fish (contains KLH). • Pregnant or lactating women.
• Patients with inadequate peripheral vein access to perform leukapheresis
• Concomitant participation in another clinical trial • An organic brain syndrome or other significant psychiatric abnormality which would comprise the ability to give informed consent, and preclude participation in the full protocol and follow-up.
• Absence of assurance of compliance with the protocol. Lack of availability for follow-up assessment.

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Erasmus Medical Center

Department of Pulmonary Medicine Rotterdam Zuid-Holland 3015 GE Netherlands

Overall Clinical Trial Officials and Contacts Joachim G Aerts, MD, PhD Principal Investigator

Erasmus Medical Center Overall Contact: Joachim G Aerts, MD, PhD +31 10 408 7703 j.aerts@sfg.nl

Related Publications

References Hegmans JP, Hemmes A, Aerts JG, Hoogsteden HC, Lambrecht BN. Immunotherapy of murine malignant mesothelioma using tumor lysate-pulsed dendritic cells. Am J Respir Crit Care Med. 2005 May 15;171(10):1168-77. Epub 2005 Mar 11.

Additional Information Information obtained from ClinicalTrials.gov on April 29, 2008 Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00280982

Study ID Number: MEC-2005-269 ClinicalTrials.gov

Identifier: NCT00280982

Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) Clinical Trials Authorship and Review Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org.

Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

posted by Your Attorney at 2:15 PM
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An Efficacy and Safety Study With Vandetanib to Treat Inoperable or Relapsed Malignant Mesothelioma

A clinical study to assess if a new investigational drug is effective in treating malignant mesothelioma, compared to a chemotherapy treatment (Navelbine®). In this study the patients will be assigned by chance to receive either the new drug or a chemotherapy treatment (Navelbine®). Treatment will continue as long as the cancer does not worsen and the patient wishes to continue in the study…

Date First Received: January 9, 2008

Last Updated: April 23, 2008

Verified by: AstraZeneca, April 2008

Clinical Trial Phase: Phase 2 Start Date: December 2007

Overall Status: Recruiting

Estimated Enrollment: 66

Brief Summary Official Title: “A Randomized Phase II Trial To Evaluate The Efficacy And Safety Of Vandetanib (ZD6474, ZACTIMA ™) Versus Vinorelbine In Patients With Inoperable Or Relapsed Malignant Mesothelioma.”

Condition Keyword(s):

• Mesothelioma

Intervention(s):

• Drug: Vinorelbine
• Drug: Vandetanib

A clinical study to assess if a new investigational drug is effective in treating malignant mesothelioma, compared to a chemotherapy treatment (Navelbine®). In this study the patients will be assigned by chance to receive either the new drug or a chemotherapy treatment (Navelbine®). Treatment will continue as long as the cancer does not worsen and the patient wishes to continue in the study. The study will recruit approximately 66 patients.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study Outcome Measures for this Clinical Trial

Primary:

• To evaluate the efficacy of vandetanib compared with vinorelbine by estimating the Overall Disease Control Rate (DCR=CR+PR+SD) Assessed from baseline to week 12

Secondary:

• To estimate the Overall Objective Response Rate (ORR=CR+PR), Progression-Free Survival (PSF) and Overall Survival (OS). time to progression and death
• To further characterise the safety profile of vandetanib. Quality of life over time assessed from baseline to week 12

Criteria for Participation in this Clinical Trial Inclusion Criteria:

• Men or women aged 18 or over
• Diagnosed with mesothelioma
• Previously treated with only one course of chemotherapy for mesothelioma
• No previous treatment with vinorelbine
• No serious heart problems within the last 3 months

Exclusion Criteria:

• Serious abnormal laboratory values
• Severe or uncontrolled disease or condition as judged by the Investigator
• Pregnant or breast-feeding women
• Other cancers within the last 5 years
• Major surgery or radiation therapy within 4 weeks prior to starting study therapy
• Receipt of any investigational agents within 30 days prior to commencing study treatment.

Clinical Trials Locations, Contact Details, and Sponsors Lead Sponsor: AstraZeneca

Research Site Heidelberg Germany

Research Site Essen Germany

Research Site Hamburg Germany

Research Site Halle-Dolau Germany

Research Site Zurich Switzerland

Research Site Chur Switzerland

Overall Clinical Trial Officials and Contacts Rolf Stahel Principal Investigator University of Zurich Overall Contact: AstraZeneca Switzerland Clinical Study Information +0041 41 725 76 14

Additional Information Information obtained from ClinicalTrials.gov on April 29, 2008 Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00597116

Study ID Number: D4200C00075 ClinicalTrials.gov

Identifier: NCT00597116

Health Authority: Germany: Federal Institute for Drugs and Medical Devices Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org.

Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

posted by Your Attorney at 2:13 PM
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Dasatinib in Resectable Malignant Pleural Mesothelioma

Primary Objective: The primary objective of this novel phase I trial will be the level of biomarker modulation of p-Src Tyr 419 by induction dasatinib therapy in patients with resectable malignant pleural mesothelioma.

Secondary Objectives: Secondary objectives include overall and progression-free survival, tumor radiographic and pathologic response, and safety-toxicity profiles.

Date First Received: March 27, 2008
Last Updated: April 8, 2008
Verified by: M.D. Anderson Cancer Center, April 2008
Clinical Trial Phase: Phase 1 | Start Date: March 2008
Overall Status: Recruiting
Estimated Enrollment: 24

Brief Summary

Official Title: “Phase I Trial of Induction Dasatinib Therapy in Patients With Resectable Malignant Pleural Mesothelioma”

Condition Keyword(s):

• Malignant Pleural Mesothelioma Intervention(s):
• Drug: Dasatinib

Primary Objective: The primary objective of this novel phase I trial will be the level of biomarker modulation of p-Src Tyr 419 by induction dasatinib therapy in patients with resectable malignant pleural mesothelioma.

Secondary Objectives: Secondary objectives include overall and progression-free survival, tumor radiographic and pathologic response, and safety-toxicity profiles. Exploratory analyses will include additional biomarker evaluation in pre- and post-treatment tumor specimens, and serum/platelet/pleural effusion biomarker modulation.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Detailed Clinical Trial Description

THE STUDY DRUG:

DASATINIB is designed to decrease the activity of one or more proteins that are responsible for the uncontrolled growth of tumor cells. This may cause the tumor cells to die.

SCREENING TESTS:
Before you can start taking the study drug, you will have “screening tests” to help the doctor decide if you are eligible to take part in this study. The following tests and procedures will be performed: – Your complete medical history will be recorded. – You will have a physical exam, including measurement of vital signs (temperature, blood pressure, pulse, and breathing rate) and weight. You will also have a test to check the amount of oxygen in your blood. – Blood (about 3-4 teaspoons) will be drawn for routine tests. – You will be asked how well you are able to perform the normal activities of daily living (performance status evaluation). – You will have an electrocardiogram (ECG–a test that measures the electrical activity of the heart). – Blood (about 1-2 teaspoons) will be drawn to check how well your blood clots. – You will have a positron emission tomography (PET) scan to check the status of the disease. – Women who are able to have children must have a negative blood (about 1-2 teaspoons) or urine pregnancy test.

Before you begin taking dasatinib, you will also be tested to check the status of the disease and to help the doctor decide which type of surgery you will have. You will have a laparoscopy, mediastinoscopy, bronchoscopy, and either a video-assisted thoracoscopy or intraoperative ultrasound-guided core biopsy. You will be given a separate consent for each of these procedures, which will describe the procedures and any risks in detail.

Laparoscopy is a surgical procedure that uses a thin, lighted tube put through a cut (incision) in the belly to look at the abdominal organs or the female pelvic organs.

Mediastinoscopy is a surgical procedure to examine the inside of the upper chest between and in front of the lungs (mediastinum). During a mediastinoscopy, a small incision is made in the neck just above the breastbone or on the left side of the chest next to the breastbone.

Then a thin scope (mediastinoscope) is inserted through the opening. A tissue sample (biopsy) can be collected through the mediastinoscope and then examined under a microscope for lung problems, such as infection, inflammation, or cancer.

Video-assisted horacoscopy (VATS) is a procedure to take a biopsy of lung tissue through a small incision between two ribs with the aid of a thin, lighted tube (videoscope) and small surgical instruments.

For the intraoperative ultrasound-guided core biopsy of the lung, subcutaneous, and/or lymph node biopsy, a tissue sample is withdrawn from an organ or suspected tumor mass using a very thin needle and a syringe. The needle is guided while being viewed by the physician on a computed tomography (CT) scan. Any site that can be safely biopsied will be considered for the collection of tissue.

For a bronchoscopy, you will be given drugs to relax, and then a local anesthetic will be sprayed into your nose and throat to numb those areas. A slim, flexible tube with a light will be placed through your nose or mouth and into your lungs. A small brush will be fed through the tube and into your lungs. The brush will gently scrape off a sample of lung tissue. Tweezers will then be fed through the tube to collect the tissue samples. A small amount of water will be sprayed into your lungs and then suctioned out through the tube to collect additional tissue samples.

STUDY DRUG ADMINISTRATION:

If you are found to be eligible to take part in this study, you will take 2 dasatinib tablets by mouth 2 times a day for the 4 weeks before surgery (in the morning and 12 hours later).

Dasatinib may be taken with or without food, but should be swallowed with at least 1 cup (8 ounces) of water. A light meal is not required, but may help you avoid getting a stomach ache when you take your dose. Tablets must be swallowed whole and may not be broken. If vomiting occurs within 30 minutes of swallowing the tablet(s), you can take another dose. If you miss a dose of dasatinib, take it as soon as you remember on the same day. If you miss taking your dose for 12 hours, take your regular dose the next scheduled day (do not take double your regular dose to make up for the missed dose). You will be given a “pill diary” to write down when you take the study drug. You will be shown how to fill it out and asked to bring the diary with you to each clinic visit.

STUDY VISITS:

On Days 7, 14, 21, and 28, the following tests and procedures will be performed: – You will have a physical exam, including measurement of vital signs and weight. – You will also have a test to check the amount of oxygen in your blood. – Blood (about 3-4 teaspoons) will be drawn for routine tests. – You will have a performance status evaluation. – You will have an ECG. – Blood (about 1-2 teaspoons) will be drawn to check your how well your blood clots.

You will have a PET scan to check the status of the disease. This PET scan will be before your surgery, the study doctor will tell you when this will be performed.

SURGERY: After you have taken dasatinib for 28 days, you will have surgery to remove the tumor. You will continue to take the dasatinib until midnight the night before the surgery. Depending on the status of the disease, you will have either a pleurectomy or extrapleural pneumonectomy. You will be given a separate consent for these procedures, which will describe the surgery and any risks in detail.

Pleurectomy is the surgical procedure to remove the parietal pleura (the outermost lining around the lungs).

An xtrapleural pneumonectomy is a surgical procedure that removes portions of the lung, the parietal pleura (the lining of the lung), the pericardium (the lining of the heart), and the diaphragm.

During surgery, 5-6 core biopsies, if possible, will be taken from different areas of the tumor for biomarker testing.

For the CT-guided core biopsy of the lung, a tissue sample is withdrawn from an organ or suspected tumor mass using a very thin needle and a syringe. The needle is guided while being viewed by the physician on a CT scan.

LENGTH OF STUDY:

After surgery, your doctor will decide the type of treatment you should receive for your condition. If the disease responded well to the 4 weeks of dasatinib, you may be eligible to continue taking dasatinib once a day starting 4-6 weeks after your surgery. The doctor may also decide that you can take dasatinib once a day starting 4-6 weeks after receiving radiation therapy. You may continue to take dasatinib as long as you are benefitting. You will be taken off study if intolerable side effects occur or the disease gets worse.

FOLLOW-UP VISITS: If you continue to receive the study drug after surgery, you will have a physical exam and a PET scan every 8 weeks.

If you are taken off study for any reason, you will return to the clinic once a month for 3 months and every 3 months for 2 years, for the following tests and procedures: – You will have a physical exam, including measurement of vital signs. – Blood (about 1-2 teaspoons) will be drawn for routine tests. – You will have a PET/CT.

This is an investigational study. asatinib is an investigational agent and ongoing clinical trials are using this drug in malignant mesothelioma. However, these studies have only recently started, and there is no information so far that shows the drug is effective in malignant mesothelioma. Dasatinib is FDA approved and commercially available for the treatment of acute lymphoid and chronic myeloid leukemia.

However, its use in this research study is investigational. While you are on study, there will be no cost to you for dasatinib or for any tests or procedures performed solely for this research study.

Up to 24 participants will take part in this study. All will be enrolled at M. D. Anderson.

Outcome Measures for this Clinical Trial

Primary:

• The goal of this clinical research study is to learn how dasatinib affects biomarker levels in patients with malignant pleural mesothelioma that may be able to be removed by surgery. 2 Years

Secondary:

• The safety and effectiveness of this drug will also be studied. 2 Years
• IIdentifying peripheral biomarkers to measure response. 2 Years

Criteria for Participation in this Clinical Trial

Inclusion Criteria:

1. Patients with potentially resectable malignant pleural mesothelioma, IMIG stage I-III
2. Subject, age >/= 18 years
3. Performance Status (ECOG) PS 0-1
4. No prior chemotherapy for mesothelioma within the last 3 years
5. No prior radiation to the area of primary disease. Radiation to chest wall port sites is acceptable.
6. No prior targeted biologic therapy (i.e. EGFR inhibitors, VEGF inhibitors) within the last 3 years
7. Adequate Organ Function: a) Total bilirubin < 2.0 times the institutional Upper Limit of Normal (ULN), b) Hepatic enzymes (AST, ALT )
   </= 2.5 times the institutional ULN, c) Serum Na, K+, Mg2+, Phosphate and Ca2+>/= Lower Limit of Normal (LLN), d) Serum
8. Creatinine < 1.5 time the institutional ULN, e) Hemoglobin, Neutrophil count, Platelets, PT, PTT all Grade 0-1
9. Ability to take oral medication (dasatinib must be swallowed whole)
10. Women of childbearing potential (WOCBP) must have: A negative serum or urine pregnancy test (sensitivity </= 25IU HCG/L) within 72 hours prior to the start of study drug administration
11. Persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 4 weeks after study drug is stopped
12. Signed written informed consent including HIPAA according to institutional guidelines

Exclusion Criteria:

1. Malignancy [other than the one treated in this study] which required radiotherapy or systemic treatment within the past 3 years.
2. Prior therapies to be excluded: any prior chemotherapy or targeted biologic therapy for mesothelioma used within the last 3 years
3. Concurrent medical condition which may increase the risk of toxicity, including: a)
4. Clinically-significant coagulation or platelet function disorder (e.g. known von Willebrand’s disease) b) Any disease which requires persistent anticoagulation therapy (and the patient may not be taken off the anti-coagulation safely) with coumadin, factor Xa inhibitors, or heparin (low-molecular weight, standard)
5. Cardiac Symptoms, consider the following: a) Uncontrolled angina, congestive heart failure or MI within (6 months), b) Diagnosed congenital long QT syndrome: 1. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes), 2. Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec), 3. Subjects with hypokalemia or hypomagnesemia if it cannot be corrected
6. History of significant bleeding disorder unrelated to cancer, including: a) Diagnosed congenital bleeding disorders (e.g., von Willebrand’s disease), b) Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies), c) Ongoing or recent (</= 3 months) significant gastrointestinal bleeding
7. Concomitant Medications, consider the following prohibitions: a) Drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (Patients must discontinue drug 7 days prior to starting dasatinib): A) quinidine, procainamide, disopyramide, B) amiodarone, sotalol, ibutilide, dofetilide, C) erythromycin, clarithromycin, D) chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide E) cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine. F) moxifloxacin, levofloxacin
8. The concomitant use of H2 blockers or proton pump inhibitors with dasatinib is not recommended.The use of antacids should be considered in place of H2 blockers or proton pump inhibitors in patients receiving dasatinib therapy.a)Patient agrees to discontinue St. Johns Wort while receiving dasatinib therapy,b)Patient agrees that IV bisphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia,c)Patient may not be receiving any prohibited CYP3A4 inhibitors,d)Patient may not be receiving any alternative herbal remedies during the dasatinib treatment period
9. Women: a) are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after cessation of study drug, or, b) have a positive pregnancy test at baseline, or c) are pregnant or breastfeeding, d)
   Sexually active women of childbearing potential (WOCBP) must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized.
10. continued from exclusion #8-: e) Prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy., f) All

    WOCBP MUST have a negative pregnancy test prior to first receiving dasatinib. If the pregnancy test is positive, the patient must not receive dasatinib and must not be enrolled in the study.

11. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness

Clinical Trials Locations, Contact Details, and Sponsors

• Lead Sponsor: M.D. Anderson Cancer Center
• U.T.M.D. Anderson Cancer Center
• Houston Texas 77030 United States
• Overall Clinical Trial Officials and Contacts
• Anne S. Tsao, MD Principal Investigator U.T.M.D. Anderson Cancer Center
• Overall Contact: Anne S. Tsao, MD 713-792-6363

Additional Information

• Information obtained from
  ClinicalTrials.gov on April 29, 2008
• Study ID Number: 2006-0935
• ClinicalTrials.gov Identifier: NCT00652574
• Health Authority: United States: Institutional Review Board
• Clinical Trials Authorship and Review
• Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

posted by Your Attorney at 2:10 PM
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Phase II Study of Valproate and Doxorubicin in Malignant Mesothelioma

The purpose of this study is to determine the response rate to the combination of doxorubicin and valproate acid in patients with MM failing after at least one previous chemotherapy regimen including platinum derivatives…

Date First Received: March 5, 2008
Last Updated: March 5, 2008
Verified by: European Lung Cancer Working Party, March 2008
Clinical Trial Phase: Phase 2 | Start Date: July 2006
Overall Status: Recruiting
Estimated Enrollment: 41

Brief Summary

Official Title: “A Phase II Study Assessing the Activity of Valproate Acid Plus Doxorubicin in Refractory or Recurrent Malignant Mesothelioma”

Condition Keyword(s):

• Malignant MesotheliomaIntervention(s):
• Drug: Valproate plus doxorubicin

The purpose of  this study is to determine the response rate to the combination of doxorubicin and valproate acid in patients with MM failing after at least one previous chemotherapy regimen including platinum derivatives.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Efficacy Study

Outcome Measures for this Clinical
Trial

Primary:

• Response rate Every 3 courses

Secondary:

• Survival Survival will be dated from the day of registration until death or last follow up
• Toxicity After each course of chemotherapy and at the end of treatment

Criteria for Participation in this Clinical Trial

Inclusion Criteria:

Histological diagnosis of malignant mesothelioma

• Unresectable or inoperable malignant mesothelioma failing after at least one prior chemotherapy regimen including platinum derivatives (cisplatin or carboplatin)
• At least one evaluable or measurable CT-lesion
• Availability for participating in the detailed follow-up of the protocol
• Signed informed consent

Exclusion Criteria:

• Patients who are candidates for surgery with curative intent
• Patient who were previously treated with anthracyclin derivatives
• Performance status < 60 on the Karnofsky scale
• A history of prior malignant tumour, except non-melanoma skin cancer or in situ carcinoma of the cervix and cured malignant tumour (more than 5-year disease free interval)
• A history of prior HIV infection
• Polynuclear cells < 2,000/mm³• Platelet cells < 100,000/mm³
• Abnormal coagulation tests (aPTT, PTT, prothrombin time) and/or decreased fibrinogen
• Serum bilirubin >1.5 mg/100 ml
• Transaminasesmore than twice the normal range
• Serum creatinine > 1.5 mg/100 ml
• Recent myocardial infarction (less than 3 months prior to date of diagnosis)
• Congestive cardiac failure (ejectional fraction of the left ventricle < 50%) or uncontrolled cardiac arrhythmia
• Uncontrolled infectious disease
• Active epilepsy needing a specific treatment
• Concomitant treatment with IMAO, carbamazepine, mefloquine, phenobarbital, primidone, phenytoïn, lamotrigine, zidovudine
• Pregnancy or refusal to use active contraception
• A known allergy to valproate acid and/or doxorubicin
• Serious medical or psychological factors which may prevent adherence to the treatment schedule

Clinical Trials Locations, Contact Details, and Sponsors

• Lead Sponsor: European Lung Cancer Working Party
• Department of Intensive Care Unit and Thoracic Oncology Institut Jules
  Bordet
  Brussels 1000 Belgium
• Department of
  Pneumology CHU Charleroi
   Charleroi 6000 Belgium
• Department of Pneumology Hôpital Saint-Joseph
  Gilly
  6060 Belgium
• Department of Pneumology CHR St joseph
  – Warquignies
  Boussu 7360 Belgium
• CH Peltzer-La
  Tourelle
  Verviers 4800 Belgium
• Hôpital
  Ambroise Paré
  Mons 7000 Belgium
• Department of
  Pneumology Hôpital Ixelles-Molière
  Brussels Belgium
• Department of Pneumology CHRU Lille
  Lille France
• Overall Clinical Trial Officials and Contacts
• Thierry Berghmans, MD Study Chair European Lung Cancer
  Working Party

  Overall Contact: Nathalie Leclercq,
  RN 0032/2/5390496
  nathalie.leclercq@bordet.be

Additional Information

• Information obtained from ClinicalTrials.gov on April 29, 2008
• Link to the current ClinicalTrials.gov record: http://clinicaltrials.gov/show/NCT00634205
• Study ID Number: ELCWP-01062
• ClinicalTrials.gov Identifier: NCT00634205
• Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
  Click here for more information on the protocol
• Trials registry of the French National Cancer Institute
• Clinical Trials Authorship and Review
• Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

posted by Your Attorney at 2:07 PM
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Suberoylanilide Hydroxamic Acid (SAHA) Versus Placebo in Advanced Malignant Pleural Mesothelioma

This is a Phase III a study which incorporates an initial Phase II component to determine the safety, tolerability, and anti-tumor effectiveness of an oral investigational drug suberoylanilide hydroxamic acid, in the treatment of advanced malignant pleural Mesothelioma.

Date First Received: August 5, 2005
Last Updated: April 24, 2008
Verified by: Merck, April 2008
Clinical Trial Phase: Phase 2/Phase 3 | Start
Date: July 2005
Overall Status: Recruiting
Estimated Enrollment: 660

Brief Summary

Official Title: “A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Oral Suberoylanilide Hydroxamic Acid (SAHA) in Patients With Advanced Malignant Pleural Mesothelioma Previously Treated With Systemic Chemotherapy”

Condition Keyword(s):

• Mesothelioma
• Lung Cancer

Intervention(s):

• Drug: Suberoylanilide Hydroxamic Acid (SAHA)
• Drug: Placebo (unspecified)

This is a Phase III a study which incorporates an initial Phase II component to determine the safety, tolerability, and anti-tumor effectiveness of an oral investigational drug suberoylanilide hydroxamic acid, in the treatment of advanced malignant pleural Mesothelioma.

Revised (20-Dec-2007)

Study Type: Interventional

Study Design: Treatment,

Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Outcome Measures for this Clinical Trial

Primary:

• Overall survival and safety/toxicity after 14 consecutive day treatment followed by 7 days of rest repeated in 21 day cycles until disease progression or unacceptable toxicity. Up to 24 weeks of treatment

Secondary:

• Overall objective response, response duration,
  progression-free-survival dyspnea score on LCSS-Meso and
  Forced Vital Capacity change. Treatment will continue
  until disease progression or unacceptable toxicity. Up
  to 24 weeks of treatment

Criteria for
Participation in this Clinical Trial

Inclusion Criteria:

• Patient must be 18 years or older with confirmed diagnosis of malignant pleural mesothelioma.
• Patient must have failed prior chemotherapy that included pemetrexed with either cisplatin or carboplatin.
• Patient must have adequate bone marrow, liver and kidney function.
• Patient must be capable of self-care and out of bed for more than 50% of waking hours.
• Patient must have ability to swallow pills.

Exclusion Criteria:

• Patient has been
  treated with other investigational agent that has
  similar properties
• Patient has an active
  infection within 2 weeks of the start of study drug, or
  had treatment with intravenous antibiotic, antiviral, or
  antifungal medications within 2 weeks of the start of
  study drug.
• Patient is pregnant or breast feeding

Clinical Trials Locations, Contact Details, and Sponsors

• Lead Sponsor: Merck
  Call for Information
  Pittsburgh Pennsylvania 15232 United States
• Merck Sharp & Dohme B.V.
  Bruxelles 1180 Belgium
• Msd Sharp & Dohme Gmbh
  Haar 85540 Germany
• Merck Sharp & Dohme B.V.
  Haarlem 2031 BN Netherlands
• Merck Sharp & Dohme (New Zealand) Ltd.,
  Auckland
  New Zealand
• Merck Sharp & Dohme De Espana, S.A.E.
  Madrid 28027 Spain
• Merck Sharp & Dohme (Sweden) AB
  Sollentuna 192 07 Sweden
• Merck Sharp & Dohme Ltd.
  Hoddesdon Hertfordshire EN11 9BU United Kingdom

Overall Clinical Trial Officials and Contacts

• Medical Monitor Study Director Merck
  Overall
  Contact: Toll Free Number 1-888-577-8839
• Additional Information Information obtained from ClinicalTrials.gov on April 29, 2008
• Link to the current ClinicalTrials.gov record.
  http://clinicaltrials.gov/show/NCT00128102
• Study ID Number: 2005_010
• ClinicalTrials.gov Identifier: NCT00128102
• Health Authority: United States: Food and Drug Administration
• (MedWatch – FDA maintained medical product safety Information)
• (PhRMA Clinical Study Results Database – web-based repository for clinical study results)
• (Merck: Patient & Caregiver U.S. Product Web Site)

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

posted by Your Attorney at 2:05 PM
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Early Diagnosis of Lung Cancer and Mesothelioma in Prior Asbestos Workers

Occupational exposure to asbestos is known increase the risk of developing cancer of the lungs (bronchogenic carcinoma) or of the pleura (mesothelioma). Symptoms are subtle and non-specific, diagnosis is often late and the prognosis consequently is dismal. Currently there is no accepted non-invasive tool for the early diagnosis of mesothelioma or lung cancer in asbestos-exposed subjects.

Date First Received: September 12, 2005
Last Updated: October 31, 2007
Verified by: University Health Network, Toronto, October 2007
Clinical Trial Phase: N/A | Start Date: March 2005
Overall Status: Recruiting
Estimated Enrollment: 1000

Brief Summary

Official Title: “Early Diagnosis of Mesothelioma and
Lung Cancer Following Asbestos Exposure Using Low-Dose
Computed Tomography”

Condition Keyword(s):

• Lung Cancer
• Mesothelioma

Occupational exposure to asbestos is known increase the risk of developing cancer of the lungs (bronchogenic carcinoma) or of the pleura (mesothelioma). Symptoms are subtle and non-specific, diagnosis is often late and the prognosis consequently is dismal. Currently there is no  accepted non-invasive tool for the early diagnosis of mesothelioma or lung cancer in asbestos-exposed subjects. In the last decade, low-dose computed tomography (LDCT) has been successfully developed and validated for the early diagnosis of lung cancer in high-risk smokers. Malignant mesothelioma might, in an early stage, resemble a benign pleural plaque, which is a common finding after asbestos exposure. We target to develop low-dose CT as a tool to serially image the pleural plaques, quantify their individual and overall volume, compute the growth rate with time, and, as such, identify the presence of mesothelioma early, before
symptoms occur.

Study Type: Observational

Study Design: Case Control, Other

Criteria for Participation in this Clinical Trial

Inclusion Criteria:

• prior asbestos exposure at least 20 years ago and/or documented pleural plaques (chest x-ray evidence)
• Resident of Ontario, Canada

Exclusion Criteria:

• prior cancer (except non-melanotic
  skin cancer)

Clinical Trials Locations, Contact Details, and Sponsors

• Lead Sponsor: University 
• Health Network, Toronto
• Princess Margaret Hospital
• Toronto Ontario Canada

Overall Clinical Trial Officials and Contacts

• Demetris Patsios, MD
  Principal Investigator University Health Network,
  Toronto
• Overall Contact: Demetris Patsios, MD
  Tel: (416) 603-5800
  demetris.patsios@uhn.on.ca

Additional Information

• Information obtained from ClinicalTrials.gov on April 29, 2008
• Link to the current ClinicalTrials.gov record.  http://clinicaltrials.gov/show/NCT00188890
• Study ID  Number: Asbestos Screening Study
• ClinicalTrials.gov Identifier: NCT00188890
• Health Authority: Canada: Health Canada

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

posted by Your Attorney at 2:03 PM
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Cisplatin, Imatinib Mesylate, and Pemetrexed in Malignant Mesothelioma Patients

Primary Objective: 1. To determine the maximum tolerated dose of the combination of cisplatin, imatinib mesylate, and pemetrexed in metastatic malignant mesothelioma. Secondary Objectives: 1. To explore the biologic effects of cisplatin, imatinib mesylate, and pemetrexed on tumor tissue by: 1. histologic analysis of biopsy tissue 2. by non-invasive assessments of tumor vascularity performed…

Date First Received: November 20, 2006
Last Updated: December 18, 2007
Verified by: M.D. Anderson Cancer Center, December 2007
Clinical Trial Phase: Phase 1 | Start Date: August 2006
Overall Status: Recruiting
Estimated Enrollment: 42

Brief Summary

Official Title: “Phase I Trial of Cisplatin, Pemetrexed, and Imatinib Mesylate in Unresectable or
Metastatic Malignant Mesothelioma”

Condition Keyword(s):

• Mesothelioma

Intervention(s):

• Drug: Cisplatin
• Drug: Imatinib Mesylate
• Drug: Pemetrexed

Primary Objective:

1. To determine the maximum tolerated dose of the combination of cisplatin, imatinib mesylate, and pemetrexed in metastatic malignant mesothelioma.

Secondary Objectives:

1. To explore the biologic effects of cisplatin, imatinib mesylate, and pemetrexed on tumor tissue by:
   1. histologic analysis of biopsy tissue
   2. by non-invasive assessments of tumor vascularity performed before, during and after treatment
   3. electron microscopy analysis of endothelial cell architecture after patient treatment with imatinib mesylate
   4. To explore the effects of cisplatin, imatinib mesylate, and pemetrexed on surrogate markers in serum.
   5. To assess the rate of response to therapy.
   6. To determine the doses of the combination regimen of cisplatin, imatinib mesylate, and pemetrexed that enables de-phosphorylation of PDGF-R on malignant mesothelioma tumor cells.
   7. To determine the pharmacokinetic interaction between agents in this combination regimen.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single
Group Assignment, Safety/Efficacy Study

Detailed Clinical Trial Description

Cisplatin is used to treat different cancers, including testicular, germ cell, head and neck, bladder, and lung cancer. This drug has an atom-containing platinum, which is designed to poison cancer cells, causing them to die.

Pemetrexed is designed to block enzymes in the body that play a part in tumor growth.

Imatinib mesylate is a drug that blocks certain proteins that play a part in the development of cancer. Imatinib mesylate has also been shown to increase the effect of chemotherapy in tumor cells.

Before you can start treatment on this study, you will have what are called “screening tests.” These tests will help the doctor decide if you are eligible to take part in this study. You will have your complete medical history recorded and a physical exam, including measurement of your vital signs (temperature, pulse, breathing rate, and blood pressure) and weight. An ECOG performance status evaluation (a test looking at your ability to perform day-to-day activities) will be done. Blood will be drawn (about 3 to 4 teaspoons) through a needle in your vein for routine tests. You will be asked about any medications you are taking. Women who are able to have children must have a negative blood pregnancy test. Also, your tumor will be evaluated by  magnetic resonance imaging (MRI) or computerized tomography (CT) scans before the start of this study.

If you are found to be eligible to take part in this study, you will begin taking imatinib mesylate. Depending on when you begin treatment on this study, you may be asked to take 3, 4, or 6 tablets of imatinib mesylate by mouth once a day. Your doctor will also ask you to take folic acid tablets (or a multivitamin with folic acid) during the week before you receive your first infusion of pemetrexed and then every day while you are on this study. You will also be given an injection of vitamin B12. The vitamin B12 shot will be repeated every 9 weeks during treatment on this study. Folic acid and vitamin B12 will help to decrease the risk of severe side effects from pemetrexed.

After 1 week of imatinib mesylate and folic acid, you will receive cisplatin and pemetrexed by IV infusion. Cisplatin (given over 2 hours) and pemetrexed (given over 40 minutes) will be given on the first day of each treatment cycle for a total of 6 cycles. Each cycle is 28 days long.

Dexamethasone will also be given by vein before you receive pemetrexed. Dexamethasone will help to decrease the risk of rash and nausea that may be caused by pemetrexed. Your doctor will also ask you to take dexamethasone tablets by mouth twice a day (12 hours apart) only on Day 2 of each cycle.

Every 2 weeks during the first 3 treatment cycles, you will have a physical exam, including measurement of your vital signs and weight. You will also have a performance status evaluation. Blood will be drawn (about 3 to 4 teaspoons) through a needle in your vein for routine tests every 4 weeks. After the first 3 treatment cycles, you will have these evaluations performed every 4 weeks. Also, at every 8 weeks, your tumor will be measured by a CT or an MRI scan.

After you complete 6 treatment cycles of cisplatin and pemetrexed, you will continue to take imatinib mesylate tablets every day up to 1 month after the 6 treatment cycles. If you develop any intolerable side effects or if your disease gets worse, your treatment on this study may be delayed; the dose of the study drugs decreased until your side effects are gone; or you may be taken completely off this study. Your doctor will talk with you about any changes in your dosing schedule or in the doses of your medication after you been evaluated in the clinic

After you have completed all of your treatment, you will have what is called an end-of-study visit. At this visit, you will have a physical exam, including measurement of your vital signs and weight. You will have an ECOG performance status evaluation. You will have blood drawn (about 3 to 4 teaspoons) through a needed in your vein for routine tests. You will also have your tumor measured by CT or an MRI scan.

This is an investigational study. Both cisplatin and pemetrexed have been approved by the FDA for the treatment of malignant mesothelioma. The FDA has approved imatinib mesylate for the treatment of leukemia and certain sarcomas; however, it has been authorized by the FDA for use in research only in the treatment of malignant mesothelioma. Imatinib mesylate will be provided to you free of charge during this study. Cisplatin and pemetrexed will not be provided free of charge during this study and will be billed to you or your insurance company. Up to 42 patients will take part in this study. All will be
enrolled at M. D. Anderson.

Outcome Measures for this Clinical Trial

Primary:

• Determine the maximum tolerated dose of the combination of cisplatin,
  imatinib mesylate, and pemetrexed. 2 Years

Secondary:

• Explore the biologic effects of cisplatin, imatinib mesylate, and
  pemetrexed on tumor tissue by histologic analysis of
  biopsy tissue. 2 Years
• Explore the biologic effects of cisplatin, imatinib mesylate, and
  pemetrexed on tumor tissue by non-invasive assessments
  of tumor vascularity. 2 Years
• Explore the biologic effects of cisplatin, imatinib mesylate, and
  pemetrexed on tumor tissue by electron microscopy
  analysis of endothelial cell architecture. 2 Years
• Explore the effects of cisplatin, imatinib mesylate, and pemetrexed
  on surrogate markers in serum. 2 Years
• Assess the rate of response to therapy. 2 Years
• Determine the doses of the combination regimen of cisplatin,
  imatinib mesylate, and pemetrexed that enables de-phosphorylation
  of PDGF-R on malignant mesothelioma tumor cells. 2 Years
• Determine the pharmacokinetic interaction between agents in this
  combination regimen. 2 Years

Criteria for Participation in this Clinical Trial

Inclusion Criteria:

1. A written, voluntary informed consent form must be completed
   prior to beginning any study procedure.
2. Patients >/= 18 years of age.
3. Histologically documented diagnosis of malignant mesothelioma.
4. Performance status 0-2 (ECOG)
5. Pts must have adequate hepatic,renal,& bone marrow function,defined as the following:(1) total bilirubin </=1.5xULN;(2) SGOT & SGPT</=2.5xULN;(3)creatinine </= 1.5xULN;(4) ANC >/= 1.5×10^9/L;(5) platelets>/=100 x 10^9/L.Note:Renal function is only based on serum creatinine level </= 1.5xULN.The standard Cockcroft & Gault formula or the measured glomerular filtration rate (GFR) using the appropriate radiolabelled method (51-CrEDTA or Tc99m-DTPA) must be used to calculate CrCl for enrollment or dosing.The same method used @ baseline should be used throughout the study.CrCl should be >/= 45mg/dl.
6. Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug.
7. Patients who have not received prior chemotherapy for their metastatic or recurrent unresectable malignant mesothelioma; with the exception of patients who have
   recurrent mesothelioma after induction chemotherapy followed by definitive treatment (surgery +/- radiotherapy). Patients must have had 2 or fewer cycles/doses of induction chemotherapy and must have had tumor response to the induction therapy.
8. Patients must have documented unresectable malignant mesothelioma (pleural or peritoneal).
9. Patients with treated brain metastasis who have stable brain disease (i.e. no steroids at least 4 weeks prior to study enrollment).

Exclusion Criteria:

1. Patient has received any other investigational agents within 28 days of first day of study drug dosing.
2. Patient is </= 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer, squamous skin cancer, or a cervical carcinoma in situ.
3. Patient with Grade III/IV cardiac problems as defined by the New York Heart
4. Association Criteria. (i.e., congestive heart failure)
5. Patients with myocardial infarction within 6 months of study.
6. Female patients who are pregnant or breast-feeding.
7. Patient has a severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection).
8. Patient has a known untreated or unstable brain metastasis.
9. Patient has known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis).
10.  Patient has a known diagnosis of human immunodeficiency virus (HIV) infection. HIV patients are at much greater risk of infection when receiving highly myelosuppressive agents (cisplatin, pemetrexed, and imatinib) and for safety reasons are not eligible for this trial.
11. Patient who received prior chemotherapy for their malignant mesothelioma with the exception listed in inclusion criteria #7.
12. Patient previously received radiotherapy to >/= 25 % of the bone marrow.
13. Patient had a major surgery within 2 weeks prior to study entry.
14. Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
15. Patients must agree not to use herbal remedies or other over-the-counter biologics (i.e. shark cartilage).
16. Prior exposure to imatinib mesylate.
17. Patients taking therapeutic levels of warfarin. However, patients receiving 1 mg daily for catheter related anticoagulation are eligible for the study.

Clinical Trials Locations, Contact Details, and Sponsors

• Lead Sponsor: M.D. Anderson Cancer Center
• U.T.M.D. Anderson Cancer Center
  Houston Texas 77030 United States

Overall Clinical Trial Officials and Contacts

• Anne S. Tsao, MD Principal Investigator U.T.M.D. Anderson Cancer Center
• Overall Contact: Anne S. Tsao, MD 713-792-6363

Additional Information

• Information obtained from ClinicalTrials.gov on April 29, 2008
• Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00402766
• Study ID Number: 2005-0288
• ClinicalTrials.gov Identifier: NCT00402766
• Health Authority: United States: Food and Drug Administration

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National
Institutes of Health via ClinicalTrials.gov and is not
reviewed separately by ClinicalTrialsFeeds.org. Every
page of specific clinical trials information contains a
unique identifier which can be used to find further
details directly from the National Institutes of Health.

Labels: ClinicalTrial

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Study of Patients With Non-Small Cell Lung Cancer, Esophageal Cancer, or Malignant Pleural Mesothelioma

Study of Patients With Non-Small Cell Lung Cancer, Esophageal Cancer, or Malignant Pleural Mesothelioma

Date First Received: March 13, 2007

Last Updated: December 25, 2007

Verified by: National Cancer Institute (NCI), March 2007

Clinical Trial Phase: N/A | Start Date: November 2005

Overall Status: Recruiting

Estimated Enrollment: 375

Brief Summary

Official Title: “Prospective Evaluation of Epigenetic Alterations in Patients With Lung and Esophageal Cancers and Malignant Pleural Mesotheliomas”

Condition Keyword(s):

• Esophageal Cancer
• Lung Cancer
• Malignant Mesothelioma

Intervention(s):

• Procedure: DNA methylation analysis
• Procedure: bronchoalveolar lavage
• Procedure: bronchoscopy
• Procedure: diagnostic procedure
• Procedure: endoscopic biopsy
• Procedure: gene expression analysis
• Procedure: needle biopsy

RATIONALE: Collecting and storing samples of tissue, blood, and urine from patients with cancer to study in the laboratory may help the study of cancer. It may also help doctors identify patients who are eligible for clinical trials.

PURPOSE: This study is collecting and examining tissue, blood, and urine samples from patients with non-small cell lung cancer, esophageal cancer, or Malignant Pleural Mesothelioma.

Study Type: Interventional

Study Design: Diagnostic

Detailed Clinical Trial Description

OBJECTIVES: - Evaluate patients referred to the Thoracic Oncology Section of the Surgery Branch, NCI in order to identify patients who are suitable candidates for clinical research protocols. – Obtain biopsies during staging studies of tumor and adjacent normal tissues as well as serum and urine samples from patients with primary aerodigestive tract malignancies to support preclinical research endeavors in the Thoracic Oncology Section. – Permit standard treatment for patients who are not eligible for investigational therapy on a current Thoracic Oncology protocol, but who present a novel and unique clinical training opportunity, or who manifest a clinical condition that requires immediate intervention to prevent compromise to the patient’s well-being.

OUTLINE: This is a prospective study.

Patients undergo bronchoscopy and/or bronchoalveolar lavage (BAL). Tumor tissue and normal tissue are collected via endoscopy, fine-needle aspiration, core-needle techniques, or single-port site thoracoscopic methods. Biopsies and BAL fluids are examined for gene expression and DNA methylation analysis. Blood and urine are also collected.

PROJECTED ACCRUAL: A total of 375 patients will be accrued for this study.

Outcome Measures for this Clinical Trial

Primary:

• Identification of patients who are suitable candidates for clinical research protocols
• Biopsies

Criteria for Participation in this Clinical Trial

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed or radiographic evidence of primary non-small cell lung cancer, esophageal cancer, or malignant pleural mesothelioma
• Intracranial metastases potentially treatable with surgery and/or radiotherapy allowed

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Normal coagulation parameters

PRIOR CONCURRENT THERAPY:

• Not specified

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: National Cancer Institute (NCI)

Warren Grant Magnuson Clinical Center – NCI Clinical Trials Referral Office

Bethesda Maryland 20892-1182 United States

Overall Clinical Trial Officials and Contacts

David S. Schrump, MD Study Chair NCI – Surgery Branch

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00447447

Study ID Number: CDR0000456443

ClinicalTrials.gov Identifier: NCT00447447

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute’s PDQ® database

Web site for additional information

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

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Pemetrexed, Cisplatin, and Vitamin B12 in Treating Patients With Mesothelioma of the Chest That Cannot Be Removed by Surgery

Pemetrexed, Cisplatin, and Vitamin B12 in Treating Patients With Mesothelioma of the Chest That Cannot Be Removed by Surgery

Date First Received: October 5, 2007

Last Updated: December 25, 2007

Verified by: National Cancer Institute (NCI), October 2007

Clinical Trial Phase: Phase 2 | Start Date: June 2007

Overall Status: Recruiting

Estimated Enrollment: 60

Brief Summary

Official Title: “Phase 2 Pharmacological Study of Pemetrexed Administered With Cisplatin and a Vitamin Supplement in Patients With Nonresectable Pleural Mesothelioma”

Condition Keyword(s):

• Malignant Mesothelioma

Intervention(s):

• Drug: cisplatin
• Drug: pemetrexed disodium
• Drug: vitamin B12
• Procedure: chemoprotection
• Procedure: chemotherapy
• Procedure: diagnostic procedure
• Procedure: enzyme inhibitor therapy
• Procedure: gene expression analysis
• Procedure: laboratory biomarker analysis
• Procedure: pharmacological study

RATIONALE: Pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving pemetrexed together with cisplatin and vitamin B12 may kill more tumor cells.

PURPOSE: This phase II clinical trial is studying how well giving pemetrexed together with cisplatin and vitamin B12 works in treating patients with mesothelioma of the chest that cannot be removed by surgery.

Study Type: Interventional

Study Design: Treatment, Non-Randomized

Detailed Clinical Trial Description

OBJECTIVES:

• Primary - Define an individually adapted (by dosage) protocol of pemetrexed disodium, cisplatin, and vitamin B12 in patients with unresectable pleural mesothelioma.
• Secondary – Determine the relationship between pharmacokinetic and pharmacodynamic parameters (hematologic and nonhematologic). – Analyze the inter-individual pharmacokinetic variations and the influence of the covariables on the pharmacokinetics of pemetrexed disodium. – Analyze the impact of pharmacogenetic (MTHFR, TS, GSTpi, ERCC1, XPD) variations on the toxicity of pemetrexed disodium. – Validate a strategy of adapting dosage.

OUTLINE: This is a multicenter study.

Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive vitamin B12 intramuscularly on day -7 and then every 9 weeks until chemotherapy is completed.

Blood samples are collected during the first and third courses of chemotherapy. Samples are analyzed by pharmacogenetic (MTHFR, TS, GSTpi, ERCC1, xPD), pharmacokinetic, and other pharmacological methods.

Outcome Measures for this Clinical Trial

Primary:

• Individual dosage-adapted protocol

Secondary:

• Relationship between pharmacokinetic and pharmacodynamic parameters
• Pharmacokinetics
• Pharmacogenetic variations (MTHFR, TS, GSTpi, ERCC1, XPD)

Criteria for Participation in this Clinical Trial

DISEASE CHARACTERISTICS:

Inclusion criteria:

• Histologically confirmed pleural mesothelioma
• Unresectable disease

Exclusion criteria:

• Clinically detected pleural effusion or ascites that cannot be controlled by drainage or other procedures

PATIENT CHARACTERISTICS:

Inclusion criteria:

• WHO performance status 0-2
• Life expectancy > 3 months
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Creatinine clearance > 45 mL/min
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• Transaminases ≤ 3 times ULN (5 times ULN if liver metastases)
• Not pregnant or nursing
• Fertile patients of must use effective contraception during and for 6 months after completion of study treatment

Exclusion criteria:

• Hypersensitivity to pemetrexed disodium or any of its excipients
• Peripheral neuropathy ≥ grade 2
• Impossible to receive study therapy due to geographical, social, familial, or psychological reasons

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

• At least 28 days since prior radiotherapy (21 days for injected radiotherapy)

Exclusion criteria:

• Prior chemotherapy
• Prior yellow fever vaccine
• Inability to discontinue aspirin (> 1.3 g/day) or NSAIDs for 2 days prior to, during, and 2 days after day 1 of each course of study therapy
• Concurrent participation in another clinical study

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Centre Oscar Lambret

Centre Oscar Lambret

Lille 59020 France

Overall Clinical Trial Officials and Contacts

Amelie Lansiaux, MD, PhD Centre Oscar Lambret

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00541073

Study ID Number: CDR0000564058

ClinicalTrials.gov Identifier: NCT00541073

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute’s PDQ® database

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

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Cisplatin, Pemetrexed and Bevacizumab for Untreated Malignant Mesothelioma

Date First Received: February 22, 2006
Last Updated: September 15, 2006
Verified by: University of Texas Southwestern Medical Center
Clinical Trial Phase: Phase 2 Start Date: February 2006
Overall Status: Recruiting
Estimated Enrollment: 65

Brief Summary

Condition Keyword(s): Mesothelioma

Intervention(s):
Drug: bevacizumab
Drug: cisplatin
Drug: pemetrexed

Rationale

To estimate the time to progression of cancer in patients with previously untreated mesothelioma receiving cisplatin, pemetrexed and bevacizumab

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Secondary endpoints will include:

• objective response rate
• overall survival
• In addition, the objective of the analysis of the correlative science data is to determine any association between tumor expression of VEGF/KDR complex and/or the presence of sv40 (as detected by PCR amplification) and objective response.

Outcome Measures for this Clinical Trial

Primary: progression free survival

Secondary: response rate; overall survival

Inclusion criteria

• 5.2.1 Patients must have histologically proven malignant mesothelioma (epithelial, sarcomatoid, or mixed subtype) not amenable to curative surgery or radiotherapy. Eligible sites of origin include the pleura, peritoneum, and tunica vaginalis.
• 5.2.2 Patient’s disease must not be amenable to curative treatment with surgery. Evidence of gross unresectability will include but not be limited to direct extension into the chest wall, mediastinal or hilar lymphadenopathy, pulmonary or cardiac function that is inadequate to tolerate resection, and sarcomatoid or mixed histology.
• 5.2.3 Patients must be > 18 years old 5.2.4 Patients must have measurable disease.
• Adequate organ function and functional status

Exclusion Criteria

• 5.3.1 Patients must not be pregnant or breast feeding.
• 5.3.2 No “currently active” second malignancy other than non-melanoma skin cancer. Patients are not considered to have a “currently active” second malignancy if they have completed therapy and have a less than 30% risk of relapse.
• 5.3.3 No uncontrolled intercurrent illness including but not limited to: active infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric/social situations that would limit compliance with study requirements.
• 5.3.4 No HIV positive patients receiving combination anti-retroviral therapy because of possible pharmacokinetic interactions with study medications.
• 5.3.5 History of allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab or other agents used in the study.
• 5.3.6 Inability to interrupt aspirin or other non-steroidal medication for a 5 day period.
• 5.3.7 Patients with brain metastases are excluded
• 5.3.8 History of myocardial infarction or CVA (stroke) within 6 months of study entry.
• 5.3.9 Evidence of bleeding diathesis or coagulopathy. Patients on therapeutic doses of coumadin are eligible as long as the INR is maintained in the range of 2-3 and there is no evidence of active bleeding.
• 5.3.10 Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study 5.3.11 1.0 at screening (see appendix F for³Urine protein:creatinine ratio instructions on calculating the ratio) 5.3.12 Serious, non-healing wound, ulcer, or bone fracture

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: University of Texas Southwestern Medical Center
University of Texas Southwestern Medical Center
Dallas Texas 75390-8852 United States

Overall Clinical Trial Officials and Contacts: Jonathan E Dowell, MD Principal Investigator University of Texas Southwestern

Overall Contact: Jonathan E Dowell, MD 214-648-4180 jonathan.dowell@utsouthwestern.edu

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00295503

Study ID Number: AVF3442S

ClinicalTrials.gov Identifier: NCT00295503

Labels: ClinicalTrial

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Immunotoxin Therapy, Pemetrexed, and Cisplatin in Treating Patients With Malignant Pleural Mesothelioma That Cannot Be Removed by Surgery

Date First Received: December 15, 2007
Last Updated: April 1, 2008
Verified by: National Cancer Institute (NCI), March 2008
Clinical Trial Phase: Phase 1 Start Date: June 2007
Overall Status: Recruiting
Estimated Enrollment: 24

Condition Keyword(s): Malignant Mesothelioma

Intervention(s):
Drug: SS1(dsFv)-PE38 immunotoxin
Drug: cisplatin
Drug: pemetrexed disodium
Procedure: chemotherapy
Procedure: immunoenzyme technique
Procedure: immunohistochemistry staining method
Procedure: immunotoxin therapy
Procedure: pharmacological study
Procedure: quality-of-life assessment

Rationale

Immunotoxins can find tumor cells and kill them without harming normal cells.

Drugs used in chemotherapy, such as pemetrexed and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Giving more than one drug (combination chemotherapy) together with immunotoxin therapy may kill more malignant mesothelioma cells.

PURPOSE: This phase I trial is studying the side effects and best dose of immunotoxin therapy when given together with pemetrexed and cisplatin in treating patients with malignant pleural mesothelioma that cannot be removed by surgery.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Active Control

OBJECTIVES
Primary – To estimate the maximum tolerated dose (MTD) of SS1(dsFv)-PE38 immunotoxin when administered with pemetrexed disodium and cisplatin and to establish a safe dose, based on the MTD for subsequent clinical testing (phase II recommended dose) in patients with unresectable malignant epithelial pleural mesothelioma. – To characterize the toxicity profile of SS1(dsFv)-PE38 immunotoxin. – To study the clinical pharmacology (i.e., pharmacokinetics) which may dictate modification of SS1(dsFv)-PE38 immunotoxin schedule and administration in future studies. – To observe antitumor activity, if any, especially in patients who receive SS1(dsFv)-PE38 immunotoxin at or near the MTD (or phase II recommended dose).

Secondary – To monitor antibody formation to SS1(dsFv)-PE38 immunotoxin and to assess the impact of these antibodies on SS1(dsFv)-PE38 immunotoxin pharmacokinetics (PKs). – To investigate the potential of soluble mesothelin levels to predict PKs or any therapeutic or toxic response. – To perform a pilot assessment of a validated quality of life instrument.

OUTLINE
This is a dose-escalation study of SS1(dsFv)-PE38 immunotoxin.

Patients receive SS1(dsFv)-PE38 immunotoxin IV over 30 minutes on days 1, 3, and 5, pemetrexed disodium IV over 10 minutes on day 1, and cisplatin IV over 2 hours on day 1 in courses 1 and 2. Beginning in course 3 and all subsequent courses, patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection at baseline, prior to course 2, and day 21 of course 2 for laboratory and pharmacokinetic studies. Samples are analyzed for the presence of anti-SS1(dsFv)-PE38 immunotoxin antibodies using a study drug-specific immunoassay and for concentrations of circulating mesothelin using enzyme-linked immunosorbent assay. Tumor cells from archival paraffin block biopsy specimens are analyzed for expression of mesothelin via immunohistochemistry.

Patients complete a quality of life questionnaire (i.e., LCSS-MESO) at baseline, after course 2, and subsequently after every even course to assess symptoms including appetite loss, fatigue, cough, dyspnea, and pain.

After completion of study treatment, patients are followed at 1, 3, 6, 12, 15, 18, 21, and 24 months.

Outcome Measures for this Clinical Trial

Primary:

• Maximum tolerated dose of SS1(dsFv)-PE38 immunotoxin
• Pharmacokinetics of SS1(dsFv)-PE38 immunotoxin
• Antitumor response

Secondary: Measurement of antibody formation to drug and impact on pharmacokinetics

DISEASE CHARACTERISTICS

• Histologically confirmed epithelial pleural mesothelioma not amenable to potentially curative surgical resection
• Unresectable disease, defined as any 1 of the following:
  • Metastatic disease
  • Patient found at surgery not to be amenable to resection
  • Not to benefit from surgery due to extensive local disease or not a surgical candidate due to comorbid medical conditions as deemed by a qualified oncologist
  • Measurable disease
• No documented and ongoing CNS involvement with malignant disease (history of CNS involvement is not an exclusion criterion)

PATIENT CHARACTERISTICS

Inclusion criteria:

• Karnofsky performance status 70-100%
• Life expectancy > 3 months (assessed by the principal investigator)
• ALT, AST, or bilirubin ≤ grade 1 (unless due to cancer or Gilbert disease) OR ≤ grade 2 (if due to cancer)
• Serum creatinine clearance ≥ 60 mL/min
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• FEV_1 ≥ 50% of predicted value (post-pleural drainage and bronchodilation if these are indicated)
• Must be able to understand and sign informed consent
• Other (non-mesothelioma) cancers that meet eligibility criteria and have had less than 5 years of disease-free survival are considered on a case by case basis
• May only be enrolled in this study once (i.e., no second time or later cohort re-enrollment)

Exclusion criteria:

• Clinically significant heart disease (New York Heart Association class III or IV)
• Active bacterial or fungal infection
• Baseline coagulopathy ≥ grade 3 (unless due to anticoagulant therapy)
• HIV-positive serology
• Hepatitis B surface antigen positivity
• Uncontrolled, symptomatic, intercurrent illness including, but not limited to, any of the following:
  • Infections requiring systemic antibiotics
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness or social situation that would limit compliance with study requirements

PRIOR CONCURRENT THERAPY:

• More than 4 weeks since prior radiotherapy (except palliative extra-thoracic localized radiotherapy) or biologic therapy for malignant pleural mesothelioma
• More than 2 weeks since prior surgery or pleurodesis
• No prior systemic chemotherapy for malignant pleural mesothelioma

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: National Cancer Institute (NCI)
Warren Grant Magnuson Clinical Center – NCI Clinical Trials Referral Office
Bethesda Maryland 20892-1182 United States

Overall Clinical Trial Officials and Contacts
Raffit Hassan, MD Principal Investigator National Cancer Institute (NCI)

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00575770

Study ID Number: CDR0000579640

ClinicalTrials.gov Identifier: NCT00575770

Labels: ClinicalTrial

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Pemetrexed Disodium and Cisplatin Followed by Surgery With or Without Radiation Therapy in Treating Patients With Malignant Pleural Mesothelioma

Date First Received: June 7, 2006
Last Updated: December 25, 2007
Verified by: National Cancer Institute (NCI), October 2007
Clinical Trial Phase: Phase 2 Start Date: November 2005
Overall Status: Recruiting
Estimated Enrollment: 155

Condition Keyword(s): Malignant Mesothelioma

Intervention(s):
Drug: cisplatin
Drug: pemetrexed disodium
Procedure: adjuvant therapy
Procedure: chemotherapy
Procedure: conventional surgery
Procedure: diagnostic procedure
Procedure: enzyme inhibitor therapy
Procedure: laboratory biomarker analysis
Procedure: neoadjuvant therapy
Procedure: quality-of-life assessment
Procedure: radiation therapy

Rationale

Drugs used in chemotherapy, such as pemetrexed disodium and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This randomized phase II trial is studying how well giving pemetrexed disodium together with cisplatin followed by surgery with or without radiation therapy works in treating patients with malignant pleural mesothelioma.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label

OBJECTIVES:

Primary – Evaluate the short-term outcomes and feasibility of neoadjuvant therapy with pemetrexed disodium and cisplatin followed by extrapleural pneumonectomy in patients with malignant pleural mesothelioma. – Evaluate the long-term outcomes and feasibility of postoperative hemithoracic radiotherapy in patients with R0 or R1 resection.

Secondary – Determine the quality of life of these patients. – Identify predictive and prognostic markers in these patients. – Determine relapse-free or progression-free survival and overall survival of these patients. – Collect tissue and blood from these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, histology (sarcomatous or other vs epithelial or mixed histology), nodal status (N0-1 vs N2), and extent of disease (T1-2 vs T3). – Part 1 (neoadjuvant therapy and surgery): Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Within 8 weeks after completion of neoadjuvant therapy, patients without progressive disease undergo extrapleural pneumonectomy. – Part 2 : Patients achieving R0 or R1 resection proceed to part 2 of study treatment and are randomized to 1 of 2 treatment arms. Patients with R2 resection, disease progression, or symptomatic deterioration after treatment in part 1 are taken off study. – Arm I (no postoperative radiotherapy): Patients do not undergo radiotherapy.

Quality of life is assessed at baseline and at 6, 10, 16, and 22 weeks after randomization. – Arm II (postoperative radiotherapy): Beginning within 10 weeks after surgery, patients undergo radiotherapy to the hemithoracic region 5 days a week for approximately 5 weeks in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline and at 4, 8, 14, and 20 weeks after initiation of radiotherapy.

Patients undergo blood and tissue collection at registration and surgery for laboratory and biomarker analysis.

After completion of study treatment, patients are followed periodically for up to 5 years after surgery.

PROJECTED ACCRUAL: A total of 155 patients will be accrued for this study.

Outcome Measures for this Clinical Trial

Primary:

• Complete macroscopic resection (part 1)
• Loco-regional relapse-free survival (part 2)

Secondary:

• Response to neoadjuvant therapy (part 1)
• Adverse drug reaction to neoadjuvant therapy (part 1)
• Operability (part 1)
• Surgical complications (part 1)
• Reasons for non-randomization (part 1)
• Relapse-free or progression-free survival (part 1)
• Adverse reaction to postoperative radiotherapy (part 2)
• Late toxicity (part 2)
• Feasibility of postoperative radiotherapy (part 2)
• Relapse-free survival (part 2)
• Psychological distress (quality of life) (part 2)
• Overall survival

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed malignant pleural mesothelioma
• T1-3, N0-2, M0 disease according to International Mesothelioma Interest Group staging system
• No obvious invasion of mediastinal structures by CT scan (e.g., heart, aorta, spine, esophagus)
• No obvious widespread chest wall invasion
• Resectable chest wall lesions allowed

PATIENT CHARACTERISTICS:

• WHO performance score 0-1
• Fit for neoadjuvant therapy, surgery, and postoperative radiotherapy
• Creatinine clearance > 60 mL/min
• Hemoglobin ≥ 10.0 g/dL
• WBC ≥ 3,500/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 1.5 times ULN
• Alkaline phosphatase ≤ 1.5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for up to 12 months after completion of study treatment
• FEV_1 ≥ 40% of predicted based on spirometry and lung perfusion scan, if necessary
• No serious underlying medical condition that would preclude study requirements (e.g., active autoimmune disease or uncontrolled diabetes)

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy
• No treatment on another clinical trial within the past 30 days
• No prior pleurectomy or lung resection
• No prior radiotherapy of the lower neck, thorax, or upper abdomen
• No aspirin, cyclooxygenase-2 inhibitors, or nonsteroidal anti-inflammatory agents for 5 days prior to, during, and for 2 days after pemetrexed disodium administration
• No other concurrent experimental drugs or anticancer therapy
• No concurrent drugs that would contraindicate study drugs

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Swiss Group for Clinical Cancer Research
Universitaets Spital Zuerich
Zurich CH-8091 Switzerland

Overall Clinical Trial Officials and Contacts
Rolf A. Stahel, MD Study Chair UniversitaetsSpital Zuerich

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00334594

Study ID Number: CDR0000481153

ClinicalTrials.gov Identifier: NCT00334594

Labels: ClinicalTrial

posted by Your Attorney at 1:39 PM
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Tomotherapy Treatment for Mesothelioma

Date First Received: May 2, 2007
Last Updated: May 2, 2007
Verified by: Alberta Cancer Board, May 2007
Clinical Trial Phase: Phase 2 | Start Date: October 2006
Overall Status: Recruiting
Estimated Enrollment: 17

Brief Summary

Official Title: “Tomotherapy Treatment for Mesothelioma”

Condition Keyword(s):

• Mesothelioma

Intervention(s):

• Procedure: Tomotherapy

Mesothelioma is an incurable cancer involving the lining of the lung. Patients usually suffer progressive symptoms of shortness of breath and chest pain, until they ultimately succumb to the disease. While a very small number of patients qualify for aggressive treatment with surgery, chemotherapy and radiation, and enjoy long-term survival, the vast majority of patients have incurable disease. The treatment options currently available, including chemotherapy and radiation treatment, are only modestly effective at alleviating symptoms and improving life expectancy. This trial explores the use of new radiation technology (tomotherapy), to treat mesothelioma more aggressively than has been possible before. Tomotherapy’s ability to treat unusual shaped tumours, particularly when they are wrapped around sensitive normal tissues (the lung), enable higher doses of radiation to be used and this may improve its effectiveness. We will treat 17 patients with tomotherapy and assess the breathing, symptoms, and quality of life of the patients before and after treatment

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Historical Control, Single Group Assignment, Safety/Efficacy Study

Detailed Clinical Trial Description

Background

Malignant mesothelioma of the pleura is one of the most challenging diseases to treat in oncology. It is often associated with previous exposure to asbestos many years in the past with the mean latency period between asbestos exposure and the development of mesothelioma being approximately 48 years. The disease most commonly presents in the fifth to seventh decade of life, and the natural history is one of relentless progression and eventual death in nearly all patients. It can metastasize to regional nodes and/or distant sites, but most of the morbidity and mortality comes from local disease in the chest, causing progressive constriction, and death from pulmonary insufficiency or infection. Common clinical manifestations can include pleural effusions, superior vena cava obstruction, dysphagia, and laryngeal nerve palsy. Median survival rates are generally less than one year from the time of diagnosis, although there may be a small subset of patients with more indolent disease that have longer survival durations. Patients generally suffer from significant symptoms over the course of their illness, particularly progressive dyspnea and chest pain.

Treatment options with mesothelioma

The treatment of mesothelioma has been characterized by disappointment. The only form of “curative” treatment that has been attempted is a combination of surgery (extrapleural pneumonectomy), chemotherapy, and radiation treatment to the hemithorax. This was described by Sugerbaker, who reported 5-year survival rates of 22% of 120 patients treated.

Unfortunately, this approach is only possible for early stage disease (clinical stage I with no nodal involvement) in the absence of comorbid medical illness, and the vast majority of patients present with disease too advanced to consider this approach.

Role of radiotherapy in malignant mesothelioma:

Radiation therapy has been used with both radical and palliative intent. Radical treatment with tumoricidal doses is difficult to achieve with conventional treatment machines due to the dose limitations of normal tissues. The liver, heart, stomach, and normal lung tissue is routinely encompassed within the planning target volumes and all of these tissues have tolerances below the doses necessary to control disease. Curative (adjuvant) treatment has also been given after extrapleural pneumonectomy, which does not have the problem of underlying lung to deal with, but the other nearby normal structures are still difficult to avoid.

A main component of the problem in both curative and adjuvant radiotherapy is the presence of chest wall and diaphragm motion during radiotherapy. Breathing motion affects the chest wall and diaphragm primarily, two of the principal targets in mesothelioma. Maneuvers such as breath holding and respiratory gating, which have shown limited success in lung cancer radiotherapy, are more difficult in mesothelioma due to the presence of significant dyspnea and pain in a majority of patients. Clearly any attempt to treat the thoracic pleura with high-dose radiotherapy must either limit or at least account for this organ motion.

The published results from treating mesothelioma with primary radiotherapy have been suboptimal. High dose treatment to the hemithorax using conventional linear accelerators has typically resulted in complete loss of function of the underlying lung, with no survival benefit over palliative radiotherapy or no treatment. However, studies have suggested that specific symptoms can be effectively palliated with focused radiation treatment. Gordon et al reviewed 29 courses of palliative radiotherapy in 19 patients, with varying dose/fractionation schedules. Overall 11/29 treatment courses resulted in complete, “substantial”, or partial relief of symptoms. Furthermore, palliation of symptoms strongly correlated with doses over 40 Gy, suggesting a dose-response relationship. Other investigators have shown effective palliation with lower doses. Davis et al treated patients with 20-30 Gy in 4-10 fractions, with response rates of 60-68%. De Graaf-Strukowska showed 50% pain response rates in patients treated to a mean dose of 36 Gy at a minimum of 4 Gy per fraction.

These studies suggest that although radiation is an effective treatment modality against mesothelioma, the technical difficulties in treating the pleural space effectively limit the risk-benefit ratio.

Helical tomotherapy as a technique to treat mesothelioma

Tomotherapy is a relatively new technology which delivers intensity modulated radiation in a helical fashion, much like a spiral CT scan. Because treatment is given from all angles around a patient, the resulting dose distributions are highly conformal and effectively reduce nearby normal tissues. Mesothelioma was identified early in tomotherapy’s development as an ideal site for this technology, since the target volume is extremely difficult to treat using conventional techniques but well suited to the tangential beams of tomotherapy. A test plan using tomotherapy to “treat” a sample patient resulted in excellent dose coverage of the pleural disease with acceptable dose delivered to the ipsilateral and contralateral lungs [unpublished data]. Nevertheless, these test plans were designed on static systems in the absence of respiratory motion, so the feasibility of treatment on breathing patients remains unproven. Tomotherapy is currently in routine clinical and research use in several centres across North America, including the Cross Cancer Institute where it was commissioned in 2003.

Study Objectives

Primary Endpoint

The primary endpoint is disease-specific symptom control rate post-treatment, based on Palliation Index [Gordon 1982].

Secondary Endpoints

Overall survival Radiographic response rate at 3 months post-treatment Quality of life scores (QLQ-L30) at 1-, 3- and 6-months post-treatment Acute and subacute toxicity of treatment Feasibility of using cine-MR, using 3T-MRI, to define target volumes in mesothelioma Performance status at 1-, 3- and 6-months post-treatment Pulmonary function test results at 1-, 3- and 6-months post-treatment

Study Design

Description of the study

This is a single institution single-arm phase II study, assessing the efficacy of tomotherapy-delivered radiation in patients with symptomatic mesothelioma. Patients are treated with radiation alone (no concurrent chemotherapy), and assessed for symptoms and performance status post-therapy.

Duration of study

Based on our statistical analysis (see below), we will require 14 analyzable patients. With a potential drop-out rate of 20%, we will accrue 17 patients in total. Assuming a possible accrual rate of one patient every 1-2 months, it may take 24-34 months to complete the accrual process.

Selection of Patients

Eligibility Criteria

Histologic diagnosis of pleural mesothelioma Age>18 Life expectancy > 4 months Able to breathe comfortably in a supine position for periods of approximately 20 minutes (with or without supplemental O2) Has denied treatment with pemetrexed chemotherapy, or has evidence of progressive or refractory disease on treatment with pemetrexed.

Not eligible or has declined aggressive multimodality (surgical) management for early-stage disease Signed informed consent CT scan of chest performed within 6 weeks of study entry

Ineligibility Criteria

Any contraindications to thoracic radiotherapy In the judgment of the treating physician, inadequate pulmonary reserve to tolerate the proposed radiotherapy.

Unable to perform shallow breathing in a manner to make tomotherapy delivery possible Presence of symptomatic distant metastatic disease

Pre-treatment imaging

Pre-simulation imaging is required as part of this study in order to quantify the extent of chest wall and diaphragm movement during the breathing cycle. Two approaches to this analysis are acceptable: MR imaging (using the 3T MRI in the CBIAR facility) or CT/fluoroscopy (using equipment in the radiation oncology department). The decision on which technique to use will depend on the status of the MRI equipment for breathing assessment at the time of patient accrual.

Patient follow-up and evaluations

Baseline 1- month 3-months 6-months History/physical a a a a PFTs a a a a PS a a a a Palliation index a a a a QOL a a a a CT chest a a Planning MR imaging a

Statistical considerations

The number of patients required is based on the estimated efficacy of the proposed treatment regimen and the desired level of statistical significance. The table below indicates the relationship between these factors and the number of patients required:

Response rate Required “n” P-value 0.05 59 0.048 0.10 29 0.047 0.15 19 0.046 0.20 14 0.044 0.25 11 0.042 0.30 9 0.040

Based on the estimated response rate of the proposed treatment (ability to achieve some relief of symptoms), if “n” patients are treated then at least one patient will demonstrate a measurable response more than 95% of the time. In this study, an efficacy of 20% was chosen as a worst-case scenario, below which the treatment would likely not be offered for palliation. Therefore, 14 evaluable patients will be required to refute the null hypotheses of the treatment being ineffective.

If the true efficacy rate is higher, then the likelihood of a false negative result is lower, and an estimate of the true response rate can be learned.

Criteria for Participation in this Clinical Trial

Inclusion Criteria:

• histologic mesothelioma
• refused/ineligible for surgery or chemotherapy
• life expectancy >3 months

Exclusion Criteria:

• contraindications to thoracic radiotherapy
• unable to lie flat for duration of radiation therapy

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Alberta Cancer Board

Cross Cancer Institute

Edmonton Alberta T5N 2R8 Canada

Overall Clinical Trial Officials and Contacts

Rufus Scrimger, MD Principal Investigator Alberta Cancer Board

Overall Contact: Rufus Scrimger, MD 780-432-8517 rufusscr@cancerboard.ab.ca

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008

Study ID Number: LU-11-0077

ClinicalTrials.gov Identifier: NCT00469196

Health Authority: Canada: Health Canada

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

posted by Your Attorney at 1:35 PM
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Study of NGR-hTNF as Single Agent in Patients Affected by Advanced or Metastatic Malignant Pleural Mesothelioma

Date First Received: June 7, 2007
Last Updated: June 7, 2007
Verified by: MolMed S.p.A., June 2007
Clinical Trial Phase: Phase 2 | Start Date: May 2007
Overall Status: Recruiting
Estimated Enrollment: 27

Brief Summary

Official Title: “NGR010: A Phase II Study of NGR-hTNF Administered as Single Agent Every 3 Weeks in Patients Affected by Advanced or Metastatic Malignant Pleural Mesothelioma Previously Treated With no More Than One Systemic Therapeutic Regimen”

Condition Keyword(s):

• Mesothelioma

Intervention(s):

• Drug: NGR-hTNF

The main objective of the trial is to document the progression free survival (PFS) in advanced or metastatic malignant pleural mesothelioma patients treated with NGR-hTNF as single agent.

Safety will be established by clinical and laboratory assessment according to NCI-CTC criteria.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Historical Control, Single Group Assignment, Efficacy Study

Detailed Clinical Trial Description

This is a phase II, open-label, non-randomized study that will be conducted in patients affected by advanced or metastatic malignant pleural mesothelioma previously treated with no more than one systemic therapeutic regimen , that will be conducted using Simon’s two-stage design method.

Outcome Measures for this Clinical Trial

Primary:

• Antitumor activity defined as progression free survival (PFS)

Secondary:

• Tumor Growth Control Rate (TGCR) according to RECIST criteria
• Overall survival (OS)

Criteria for Participation in this Clinical Trial

Inclusion Criteria:

• Patients >18 years affected by malignant pleural mesothelioma previously treated with no more than one systemic therapeutic regimen
• Histologically or cytological confirmed malignant pleural mesothelioma of any of the following subtype: epithelial, sarcomatous, mixed
• Prior intrapleural cytotoxic agents including bleomycin not considered systemic chemotherapy
• ECOG Performance status 0 – 2
• Adequate baseline bone marrow, hepatic and renal function, defined as follows:
• Neutrophils > 1.5 x 109/L and platelets > 100 x 109/L
• Bilirubin
• AST and/or ALT
• AST and/or ALT
• Serum creatinine
• Absence of any conditions in which hypervoleamia and its consequences (e.g. increased stroke volume, elevated blood pressure) or haemodilution could represent a risk for the patient (take as reference
• “Technical data sheet human albumin” specifically used in Pharmacy Department for
• NGR-hTNF dilution)
• Patients may have had prior therapy providing the following conditions are met:
• Chemotherapy and radiotherapy: wash-out MolMed S.p.A. CLINICAL STUDY PROTOCOL
• Internal Code: IPR/16.B Confidential page 3 of 50 period of 28 days
• Surgery: wash-out period of 14 days
• Normal cardiac function and absence of uncontrolled hypertension
• Patients must give written informed consent to participate in the study

Exclusion Criteria:

• Concurrent anticancer therapy
• Patients may not receive any other investigational agents while on study
• Clinical signs of CNS involvement
• Patients with active or uncontrolled systemic disease/infections or with serious illness or medical conditions, which is incompatible with the protocol
• Known hypersensitivity/allergic reaction to human albumin preparations or to any of the excipients
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol
• Pregnancy or lactation. Patients – both males and females – with reproductive potential (i.e. menopausal for less than 1-year and not surgically sterilized) must practice effective contraceptive measures throughout the study. Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: MolMed S.p.A.

Istituto Europeo Oncologico

Milan Italy

Istituto Clinico Humanitas

Rozzano Milan Italy

Overall Clinical Trial Officials and Contacts

Federico Caligaris-Cappio, MD Principal Investigator Fondazione San Raffaele del Monte Tabor

Overall Contact: Federico Caligaris-Cappio, MD +39 02 2643

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008

Study ID Number: NGR010

ClinicalTrials.gov Identifier: NCT00484276

Health Authority: Italy: National Institute of Health

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

posted by Your Attorney at 1:31 PM
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Antineoplaston Therapy in Treating Patients With Advanced Mesothelioma

Date First Received: November 1, 1999
Last Updated: April 9, 2008
Verified by: National Cancer Institute (NCI), April 2008
Clinical Trial Phase: Phase 2 | Start Date: March 1996
Overall Status: Recruiting
Estimated Enrollment: 40

Brief Summary

Official Title: “Phase II Study of Antineoplastons A10 and AS2-1 in Patients With Mesothelioma”

RATIONALE: Antineoplastons are naturally-occurring substances that may also be made in the laboratory. Antineoplastons may inhibit the growth of cancer cells.

PURPOSE: This phase II trial is studying how well antineoplaston therapy works in treating patients with advanced mesothelioma.

Study Type: Interventional

Study Design: Treatment

Detailed Clinical Trial Description

OBJECTIVES: – Provide treatment with antineoplastons A10 and AS2-1 to patients with stage IV mesothelioma. – Describe the response to, tolerance to, and side effects of this regimen in these patients.

OUTLINE: Patients receive gradually escalating doses of antineoplaston A10 and antineoplaston AS2-1 IV six times per day until the maximum dose is reached.

Treatment continues for at least 3 months in the absence of disease progression or unacceptable toxicity. After 3 months, patients with stable or responding disease may continue treatment. Patients achieving complete response (CR) continue treatment for at least 8 months beyond CR.

Patients are followed every 2 months for 1 year and then every 3 months for the second year.

PROJECTED ACCRUAL: Approximately 20-40 patients will be accrued for this study.

Outcome Measures for this Clinical Trial

Primary:

• Response rate based on tumor measurements taken at 12 weeks

Secondary:

• Survival at 1, 2, and 5 years from the start of treatment

Criteria for Participation in this Clinical Trial

DISEASE CHARACTERISTICS:

• Histologically confirmed stage IV mesothelioma that is unlikely to respond to existing therapy and for which no curative therapy exists
• Evidence of disease by CT scan or MRI

PATIENT CHARACTERISTICS:

Age:

• 1 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• At least 2 months

Hematopoietic:

• WBC at least 2,000/mm^3
• Platelet count at least 50,000/mm^3

Hepatic:

• Bilirubin no greater than 2.5 mg/dL
• SGOT and SGPT no greater than 5 times upper limit of normal
• Hepatic function adequate

Renal:

• Creatinine no greater than 2.5 mg/dL
• No renal insufficiency
• No history of renal conditions that contraindicate high dosages of sodium

Cardiovascular:

• No uncontrolled hypertension
• No history of congestive heart failure
• No cardiovascular conditions that contraindicate high dosages of sodium

Pulmonary:

• No serious lung disease (e.g., chronic obstructive pulmonary disease)

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 4 weeks after study participation
• Not at high medical or psychiatric risk
• No nonmalignant systemic disease
• No active infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 weeks since prior immunotherapy and recovered
• No concurrent immunomodulatory agents

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered

Endocrine therapy:

• Concurrent corticosteroids allowed

Radiotherapy:

• At least 8 weeks since prior radiotherapy (or less if multiple tumors) and recovered

Surgery:

• Recovered from prior surgery

Other:

• Prior cytodifferentiating agents allowed
• No prior antineoplastons
• No other concurrent antineoplastic agents

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Burzynski Research Institute

Burzynski Clinic

Houston Texas 77055-6330 United States

Overall Clinical Trial Officials and Contacts

Stanislaw R. Burzynski, MD, PhD Study Chair Burzynski Research Institute

Additional Information

Information obtained from ClinicalTrials.gov on April 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00003508

Study ID Number: CDR0000066551

ClinicalTrials.gov Identifier: NCT00003508

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute’s PDQ® database

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via
ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org.
Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

posted by Your Attorney at 1:20 PM
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Mesothelioma Avastin Plus Pemetrexed-Cisplatin Study

Date First Received: March 29, 2008
Last Updated: April 2, 2008
Verified by: Intergroupe Francophone de Cancerologie Thoracique, April 2008
Clinical Trial Phase: Phase 2/Phase 3 | Start Date: February 2008
Overall Status: Recruiting
Estimated Enrollment: 445

Brief Summary

Official Title: “A Phase II-III Randomized Trial Pemetrexed-Cisplatin Chemotherapy With or Without Bevacizumab (Avastin), 15 mg/kg, for Malignant Pleural Mesothelioma (MPM)”

Our hypothesis is that the addition of bevacizumab to the standard chemotherapy treatment of MPM will improve overall survival and quality of life beyond that achieved with chemotherapy alone.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Detailed Clinical Trial Description

A phase II trial associating the reference chemotherapy (pemetrexed plus cisplatin) with bevacizumab is needed to ensure that no specific toxicity is induced by this association, and that this triplet have interesting activity. As pleural mesothélioma is a rare tumor, a phase III trial, using the survival data from the phase II part study, will be able to include a sufficient number of patients, in a reasonable period of time, to answer the question of efficacy of the anti-angiogenic triplet, providing the efficacy outcomes could be considered as favorable, at the end of the phase II part of the study.

Outcome Measures for this Clinical Trial

Primary:

• % of patients with controled disease (responder and stable patients) at 6 months 3-month

Secondary:

• Overall Survival month

Criteria for Participation in this Clinical Trial

Inclusion Criteria:

• Malignant, histologically proved, non resectable pleural Mesothelioma
• In case of pleural effusion, a talc pleurodesis, although not recommended, is allowed in accordance with current local practice, at the time of diagnostic thorascopy, with inclusion CT scan performed after pleurodesis.
• ECOG Performance status 0-2
• Mesothelioma with only pleural effusion without uni- or bidimensionally measurable disease will be eligible (adapted RECIST criteria)
• At least 18 years of age, less than 76 years of age
• Radiation therapy of thoracocentis tract (3 x 7Gy) performed before beginning medical study treatment, and the interval between thoracoscopic procedure and radiation will not exceed 28 days

Exclusion Criteria:

• Prior chemotherapy
• Brain metastasis
• History of cerebral vascular accident (CVA) or transient ischemic attack

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Intergroupe Francophone de Cancerologie Thoracique

Institut Jules Bordet

BRUXELLES 1000 Belgium

APHP – Hopital Tenon – Pneumologie

PARIS 75020 France

Centre Hospitalier – Pneumologie

Belfort 90016 France

CHU – Pneumologie

CAEN 14000 France

CHU Besancon – Pneumologie

Besancon 25000 France

CHU Grenoble – pneumologie

Grenoble 38000 France

CHU Lyautey – Pneumologie

Strasbourg 63000 France

Institut Gustave Roussy

VILLEJUIF 94805 France

APHM – Hôpital Sainte Marguerite

Marseille 13000 France

HCL – Croix-Rousse

LYON 69000 France

HCL – Lyon Sud (Pneumologie)

Pierre Bénite 69495 France

CHU Toulouse – Pneumologie

Toulouse France

Hôpital Percy-Armées – Pneumologie

Clamart 92140 France

Centre Hospitalier – Pneumologie

Le Havre 76600 France

Centre Hospitalier – Pneumologie

Le Mans 72000 France

CHU (Hôpital Calmette) – Pneumologie

Lille 59000 France

Overall Clinical Trial Officials and Contacts

Gilles Robinet, Dr Study Director GFPC

Overall Contact: Gérard Zalcman, Pr 33-2-31-06-44-76

Related Publications

References

Porret E, Madelaine J, Galateau-Sallé F, Bergot E, Zalcman G. [Epidemiology, molecular biology, diagnostic and therapeutic strategy of malignant pleural mesothelioma in 2007 - an update] Rev Mal Respir. 2007 Oct;24(8 Pt 2):6S157-64. French.

Additional Information

Information obtained from ClinicalTrials.gov on April 15, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00651456

Study ID Number: IFCT-GFPC-ELCWP-0701

ClinicalTrials.gov Identifier: NCT00651456

Health Authority: France: Afssaps – French Health Products Safety Agency

Official website

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

posted by Your Attorney at 4:22 AM
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AZD2171 in Treating Patients With Malignant Mesothelioma That Cannot Be Removed By Surgery

Date First Received: March 29, 2006
Last Updated: December 25, 2007
Verified by: National Cancer Institute (NCI), June 2007
Clinical Trial Phase: Phase 2 | Start Date: December 2005
Overall Status: Recruiting
Estimated Enrollment: 50

Brief Summary

Official Title: “Phase II Study of AZD2171 (NSC#732208) in Patients With Malignant Mesothelioma”

RATIONALE: AZD2171 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well AZD2171 works in treating patients with malignant mesothelioma that cannot be removed by surgery.

Study Type: Interventional

Study Design: Treatment, Open Label

Detailed Clinical Trial Description

OBJECTIVES:

Primary – Determine the objective response rate in patients with malignant pleural, peritoneal, or tunica vaginalis mesothelioma that is not amenable to curative surgery who are treated with AZD2171.

Secondary – Determine the progression-free survival of patients treated with AZD2171. – Determine the toxicity experienced by patients treated with AZD2171. – Determine median and overall survival of patients treated with AZD2171.

Tertiary – Generate preliminary data regarding potential utility of pharmacogenomic and plasma/serum biomarkers of angiogenesis as predictive or prognostic markers for future investigations of this drug in malignant mesothelioma.

OUTLINE: This is a multicenter study.

Patients receive oral ADZ2171 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood collection periodically during study for biomarker and optional pharmacogenomic correlative studies.

After completion of study treatment, patients are followed for up to 8 weeks.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Criteria for Participation in this Clinical Trial

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed malignant pleural, peritoneal, or tunica vaginalis mesothelioma
• Epithelial, sarcomatoid, or mixed subtype
• International Mesothelioma Interest Group stage II-IV disease (for patients with pleural mesothelioma)
• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR > 10 mm by spiral CT scan
• Pleural effusion and ascites are not considered measurable lesions
• Disease not amenable to curative surgery
• No known brain metastases

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100%
• Life expectancy > 3 months
• WBC ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Hemoglobin ≥ 8 g/dL
• Platelets ≥ 100,000/mm³
• Total bilirubin normal
• AST/ALT ≤ 2.5 times upper limit of normal (ULN)
• Creatinine normal OR creatinine clearance > 60 mL/min
• Fertile patients must use effective contraception
• Not pregnant or nursing
• Negative pregnancy test
• No history of allergic reactions to compounds of similar chemical or biologic composition to AZD2171
• Mean QTc ≤ 500 msec (with Bazett’s correction) by EKG
• No history of long QT syndrome
• Proteinuria ≤ 1+ on two consecutive dipsticks taken ≥ 1 week apart
• No other concurrent malignancy
• No New York Heart Association class III or IV cardiac disease
• No uncontrolled intercurrent illness including, but not limited to, any of the following:
• Hypertension
• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness or social situations that would limit study compliance

PRIOR CONCURRENT THERAPY:

• No more than 1 prior cytotoxic chemotherapy
• Prior intrapleural cytotoxic agents (including bleomycin) do not count towards prior cytotoxic chemotherapy
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
• No prior radiotherapy to the only site of measurable disease
• At least 4 weeks since prior radiotherapy and recovered
• At least 4 weeks since prior major surgery and recovered
• More than 30 days since prior participation in an investigational trial
• No prior treatment with a vascular endothelial growth factor (VEGF) inhibitor
• No other concurrent investigational agents
• No concurrent commercial agents for the malignancy
• No concurrent medication that may markedly affect renal function (e.g., vancomycin, amphotericin, or pentamidine)
• No concurrent hematopoietic growth factors except epoetin alfa
• No concurrent palliative radiotherapy
• No combination antiretroviral therapy for HIV-positive patients
• No concurrent drugs or biologics with proarrhythmic potential

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: University of Chicago

City of Hope Comprehensive Cancer Center

Duarte California 91010-3000 United States

City of Hope Medical Group

Pasadena California 91105 United States

Contra Costa Regional Medical Center

Martinez California 94553 United States

Tower Cancer Research Foundation

Beverly Hills California 90211-1850 United States

University of California Davis Cancer Center

Sacramento California 95817 United States

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles California 90089-9181 United States

Cardinal Bernardin Cancer Center at Loyola University Medical Center

Maywood Illinois 60153 United States

Central Illinois Hematology Oncology Center

Springfield Illinois 62701 United States

Decatur Memorial Hospital Cancer Care Institute

Decatur Illinois 62526 United States

Evanston Northwestern Healthcare – Evanston Hospital

Evanston Illinois 60201-1781 United States

Ingalls Cancer Care Center at Ingalls Memorial Hospital

Harvey Illinois 60426 United States

Oncology Hematology Associates of Central Illinois, PC – Peoria

Peoria Illinois 61615-7828 United States

University of Chicago Cancer Research Center

Chicago Illinois 60637-1470 United States

CCOP – Northern Indiana CR Consortium

South Bend Indiana 46601 United States

Fort Wayne Medical Oncology and Hematology

Fort Wayne Indiana 46885-5099 United States

Oncology Care Associates, PLLC

Saint Joseph Michigan 49085 United States

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey Pennsylvania 17033-0850 United States

Medical College of Wisconsin Cancer Center

Milwaukee Wisconsin 53226 United States

Princess Margaret Hospital

Toronto Ontario M5G 2M9 Canada

Overall Clinical Trial Officials and Contacts

Hedy L. Kindler, MD Principal Investigator University of Chicago

Additional Information

Information obtained from ClinicalTrials.gov on April 01, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00309946

Study ID Number: CDR0000463521

ClinicalTrials.gov Identifier: NCT00309946

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute’s PDQ® database

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

posted by Your Attorney at 12:06 AM
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Bortezomib in Treating Patients With Malignant Pleural Mesothelioma

Date First Received: August 8, 2007
Last updated: March 18, 2008
Verified by: National Cancer Institute (NCI), August 2007
Clinical Trial Phase: Phase 2 | Start Date: May 2006
Overall Status: Recruiting
Estimated Enrollment: 111

Brief Summary

Official Title: “An Open Label Phase II Multicentre Clinical Trial of Single Agent Bortezomib in Patients With Malignant Pleural Mesothelioma”

Condition Keyword(s):

• Malignant Mesothelioma

Intervention(s):

• Drug: bortezomib
• Procedure: enzyme inhibitor therapy
• Procedure: quality-of-life assessment

RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying the side effects of bortezomib and how well it works in treating patients with malignant pleural mesothelioma.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label

Detailed Clinical Trial Description

OBJECTIVES:

Primary – Assess the clinical efficacy of bortezomib based on the evaluation of objective tumor response rate.

Secondary – Assess additional clinical efficacy of bortezomib based on the evaluation of time to early disease progression and median overall 2-year survival rate. – Assess safety and toxicity in these patients. – Assess quality of life using the Lung Cancer Symptom Score.

OUTLINE: This is a multicenter study. Patients are stratified according to current treatment (first-line vs second-line)

Patients receive bortezomib IV on days 1, 8, 15, and 22. Treatment repeats every 5 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients exhibiting objective response or stable disease by week 20, may continue treatment at the discretion of the investigator until evidence of disease progression.

Quality of life is assessed periodically.

After completion of study treatment, patients are followed for up to 2 years.

PROJECTED ACCRUAL: 57 first-line setting and 54 second-line setting patients will be accrued for this study.

Outcome Measures for this Clinical Trial

Primary:

• Objective tumor response rate (complete response or partial response) as assessed by modified RECIST criteria

Secondary:

• Time to disease progression
• Overall survival
• Safety
• Quality of life

Criteria for Participation in this Clinical Trial

DISEASE CHARACTERISTICS:

Inclusion criteria:

• Histologically confirmed malignant pleural mesothelioma
• Meets 1 of the following criteria for first-line or second-line chemotherapy:
• Patients in the first-line setting must be unsuitable for, cannot access locally, or refuse combination chemotherapy
• Patients in the second-line setting must be unsuitable for, cannot access locally, or refuse cytotoxic chemotherapy after failure of a first-line regimen
• Second-line patients may not have received more than 1 prior line of antineoplastic treatment for this cancer
• Pleural effusions should be drained before treatment whenever possible
• Talc or tetracycline pleurodesis may be used per standard practice for uncontrollable pleural effusions (recurrent despite regular drainage)

Exclusion criteria:

• Symptomatic or known brain or leptomeningeal metastases

PATIENT CHARACTERISTICS:

Inclusion criteria:

• ECOG performance status 0-2
• Hemoglobin ≥ 10 g/dL
• Neutrophil count ≥ 1,500 mm^3
• Platelet count ≥ 100,000/mm^3
• Creatinine clearance ≥ 30 mL/min
• AST and ALT
• Fertile patients must use effective contraception during study therapy

Exclusion criteria:

• Pregnant or breastfeeding
• History of prior malignant tumor within the past 3 years except for nonmelanoma skin tumor or carcinoma in situ of the cervix
• Patients suitably fit to receive a platinum doublet based chemotherapy (first-line only)
• Uncontrolled or severe cardiovascular disease including any of the following:
• Myocardial infarction within the past 6 months
• New York Heart Association class III or IV heart failure
• Uncontrolled angina
• Clinically significant pericardial disease
• Cardiac amyloidosis
• Neuropathy ≥ grade 2 OR grade 1 with pain
• Serious medical (e.g., uncontrolled diabetes, hepatic disease, or infection) or psychiatric illness that would interfere with study participation
• Patients with known HIV or hepatitis B or C infection

PRIOR CONCURRENT THERAPY:

• No prior bortezomib
• No prior extensive radiation therapy, systemic chemotherapy, or other antineoplastic therapy within 4 weeks before enrollment
• No preplanned surgery or procedures that would interfere with the study
• More than 4 weeks since enrollment in another therapeutic clinical trial (i.e., received an experimental drug or used an experimental medical device)
• Concurrent participation in non-treatment studies is allowed provided they do not interfere with participation in this study
• No concurrent experimental or antineoplastic agent other than bortezomib
• Medications that may have antineoplastic activity, but are taken for other reasons than specific antineoplastic effect (e.g., megestrol [Megace®], cyclo-oxygenase-2 [COX-2] inhibitors, or bisphosphonates) are allowed

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Irish Clinical Oncology Research Group

Universitair Ziekenhuis Gent

Ghent B-9000 Belgium

Adelaide and Meath Hospital, Dublin Incorporating the National Children’s Hospital

Dublin 24 Ireland

Beaumont Hospital

Dublin 9 Ireland

Cork University Hospital

Cork Ireland

Galway University Hospital

Galway Ireland

Mater Misericordiae University Hospital

Dublin 7 Ireland

St. James’s Hospital

Dublin 8 Ireland

St. Vincent’s University Hospital

Dublin 4 Ireland

Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital

Amsterdam 1066 CX Netherlands

Royal Marsden – Surrey

Sutton England SM2 5PT United Kingdom

Saint Bartholomew’s Hospital

London England EC1A 7BE United Kingdom

Centre for Cancer Research and Cell Biology at Queen’s University Belfast

Belfast Northern Ireland BT9 7BL United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow Scotland G11 6NT United Kingdom

Overall Clinical Trial Officials and Contacts

Dean A. Fennell, MD, PhD Principal Investigator Centre for Cancer Research and Cell Biology at Queen’s University Belfast

Additional Information

Information obtained from ClinicalTrials.gov on April 01, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00513877

Study ID Number: CDR0000560151

ClinicalTrials.gov Identifier: NCT00513877

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute’s PDQ® database

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

posted by Your Attorney at 12:05 AM
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Bortezomib and Cisplatin as First-Line Therapy in Treating Patients With Malignant Mesothelioma

Date First Received: April 9, 2007
Last Updated: March 18, 2008
Verified by: National Cancer Institute (NCI), April 2007
Clinical Trial Phase: Phase 2 | Start Date: February 2007
Overall Status: Recruiting
Estimated Enrollment: 76

Brief Summary

Official Title: “Phase II Study of Bortezomib (VELCADE) With Cisplatin as First Line Treatment of Malignant Mesothelioma”

RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with cisplatin may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects and how well giving bortezomib together with cisplatin works as first-line therapy in treating patients with malignant mesothelioma.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label
Detailed Clinical Trial Description

OBJECTIVES: – Determine the activity and safety of bortezomib and cisplatin as first-line treatment in patients with malignant mesothelioma. – Validate the use of progression-free survival rate as a primary endpoint for the design of phase II mesothelioma trials.

OUTLINE: This is a nonrandomized, open-label, multicenter study.

Patients receive cisplatin IV over 1 hour on day 1 and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 76 patients will be accrued for this study.

Outcome Measures for this Clinical Trial

Primary:

• Progression-free survival (PFS) rate at 18 weeks

Secondary:

• Overall objective response rate
• Symptomatic response rate
• Safety as measured by NCI CTCAE v3.0 and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity questionnaire
• Duration of PFS
• Overall survival

Criteria for Participation in this Clinical Trial

DISEASE CHARACTERISTICS:

• Histologically confirmed pleural malignant mesothelioma, meeting 1 of the following criteria:
• Recurrent disease after radical surgery
• Disease not considered suitable for radical treatment
• Measurable or evaluable disease
• No clinical evidence of brain or leptomeningeal metastases

PATIENT CHARACTERISTICS:

• WHO performance status 0-1
• Life expectancy > 12 weeks
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Absolute neutrophil count > 1,500/mm³
• Platelet count > 100,000/mm³
• Creatinine clearance > 60 mL/min OR > 50 mL/min
• ALT and AST
• Bilirubin
• No concurrent secondary malignancy except carcinoma in situ of the cervix or adequately treated basal cell skin cancer
• No other malignancy treated within the past 5 years
• Melanoma, breast cancer, or hypernephroma treated within the past 5 years and without recurrence are allowed
• No uncontrolled or severe cardiovascular disease, including any of the following:
• Myocardial infarction within the past 6 months
• New York Heart Association class III-IV heart failure
• Uncontrolled angina
• Clinically significant pericardial disease or cardiac amyloidosis
• No preexisting peripheral neuropathy
• No known or suspected allergy or intolerance to boron, mannitol, or heparin, if an indwelling catheter is used
• No psychological, familial, sociological, or geographical condition that would preclude protocol compliance

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior systemic chemotherapy for mesothelioma
• No other concurrent antineoplastic agents except medications that may have antineoplastic activity but are taken for other reasons (e.g., megestrol acetate, cyclooxygenase-2 inhibitors, or bisphosphonates)
• No other concurrent experimental agents

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: European Organization for Research and Treatment of Cancer

Royal Marsden – Surrey

Sutton England SM2 5PT United Kingdom

Overall Clinical Trial Officials and Contacts

Mary O’Brien, MD Study Chair Royal Marsden – Surrey

Additional Information

Information obtained from ClinicalTrials.gov on April 01, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00458913

Study ID Number: CDR0000538677

ClinicalTrials.gov Identifier: NCT00458913

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute’s PDQ® database

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

posted by Your Attorney at 12:03 AM
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Dasatinib in Treating Patients With Previously Treated Malignant Mesothelioma

Date First Received: July 30, 2007
Last Updated: February 9, 2008
Verified by: National Cancer Institute (NCI), February 2008
Clinical Trial Phase: Phase 2 | Start Date: August 2007
Overall Status: Recruiting
Estimated Enrollment: 42

Brief Summary

Official Title: “A Phase II Study of Dasatinib (NSC #732517) in Patients With Previously Treated Malignant Mesothelioma”

RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well dasatinib works in treating patients with previously treated malignant mesothelioma.

Study Type: Interventional

Study Design: Treatment, Open Label

Detailed Clinical Trial Description

OBJECTIVES:

Primary – To determine the rate of progression-free survival (PFS) at 24 weeks (or 5.5 months) in patients with malignant mesothelioma treated with dasatinib.

Secondary – To determine the response rate (partial response [PR] and complete response [CR]) in patients with malignant mesothelioma treated with dasatinib. – To determine the response duration in patients with malignant mesothelioma treated with dasatinib. – To describe the overall survival (OS) of patients with malignant mesothelioma treated with dasatinib. – To describe the toxicity profile of dasatinib in patients with malignant mesothelioma. – To determine whether the amount of expression of EphA2 and PDGFRβ, as measured by immunohistochemistry from tumor specimens, correlates with PFS in patients with malignant mesothelioma. – To determine whether plasma levels of VEGF and PDGFRβ, serum levels of CSF-1, and soluble mesothelin-related protein correlate with PFS in patients with malignant mesothelioma. – To determine whether inhibition of Src phosphorylation in PBMC correlates with PFS. – To assess inhibition of phosphorylation of Src, EphA2, and PDGFRβ in tumor tissue by dasatinib.

OUTLINE: Patients receive oral dasatinib twice daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo tumor tissue and blood sample collection periodically for correlative studies. Tumor tissue samples are analyzed for EphA2 and PDGFRβ expression by immunohistochemistry. Tumor tissue samples may also be analyzed for phosphorylation of Src, EphA2, and PDGFRβ by western blot. Blood samples are analyzed for concentration of VEGF and PDGF by quantitative sandwich enzyme immunoassay technique; mesothelin-related protein level by Mesomark® assay; CSF-1 level by ELISA assay; and phosphorylation of Src by phospho-Src (pTyr418) human ELISA.

After completion of study treatment, patients are followed periodically.

Outcome Measures for this Clinical Trial

Primary:

• Progression-free survival (PFS) at 24 weeks (or 5.5 months)

Secondary

• Response rate (complete and partial response) as measured by RECIST criteria
• Response duration
• Overall survival
• Toxicity profile
• Correlation of expression levels of EphA2 and PDGFRβ with response, PFS, and overall survival
• Correlation of plasma levels of VEGF and PDGFRβ, serum levels of CSF-1, and soluble mesothelin-related protein with response, PFS, and overall survival
• Correlation of a decrease in Src phosphorylation in PBMC with response, PFS, and overall survival
• Correlation of a decrease in the phosphorylation of Src, EphA2, and PDGFRβ in tumor tissue with response

Criteria for Participation in this Clinical Trial

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant mesothelioma of any of the following subtypes:
• Epithelial
• Sarcomatoid
• Mixed
• Any site of origin of malignant mesothelioma allowed including, but not limited to, any of the following:
• Pleura
• Peritoneum
• Pericardium
• Tunica vaginalis
• Pathology blocks or slides from a core surgical biopsy must be available
• Not amenable to curative surgery
• Measurable disease, defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques (CT scan , MRI, or x-ray) or as ≥ 10 mm with spiral CT scan
• Patients with pleural rind only disease must have at least one level with one rind measurement ≥ 1.5 cm
• Lesions that are considered nonmeasurable include the following:
• Bone lesions
• Leptomeningeal disease
• Ascites
• Pleural/pericardial effusion
• Lymphangitis cutis/pulmonis
• Abdominal masses that are not confirmed and followed by imaging techniques
• Cystic lesions
• Prior treatment with one and only one systemic chemotherapy regimen, which must have included pemetrexed disodium required
• Treatment may have been with pemetrexed disodium alone or in combination with any other agent
• No symptomatic pleural effusions, unless the patient undergoes a therapeutic thoracentesis
• Patients with pleural effusions who have had a pleurodesis are eligible
• No known brain metastases
• Must be registered on CALGB-150707 companion study

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Granulocytes ≥ 1,500/μL
• Platelet count ≥ 100,000/μL
• Total bilirubin ≤ 2 x upper limit of normal (ULN)
• AST (SGOT) ≤ 2.5 x ULN
• Creatinine clearance ≥ 60 mL/min
• INR
• PTT
• QTc
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No significant cardiac disease, including any of the following:
• New York Heart Association (NYHA) class III-IV congestive heart failure (CHF)
• Unstable angina
• Myocardial infarction or ventricular tachyarrhythmia within 6 months of study entry
• Ejection fraction less than institutional normal (in patients with a history of CHF or currently with NYHA class I or II CHF)
• Prolonged QTc > 450 msec (Fridericia correction)
• Major conduction abnormality, unless a cardiac pacemaker is present
• Hypokalemia or hypomagnesemia that cannot be corrected
• No history of significant bleeding disorder unrelated to cancer, including any of the following:
• Congenital bleeding disorder (e.g., von Willebrand disease)
• Acquired bleeding disorder within the past year (e.g., acquired anti-factor VIII antibodies)
• Ongoing or recent (≤ 3 months) significant GI bleeding or hemoptysis
• No requirement for supplemental oxygen (i.e., pulse oximetry

PRIOR CONCURRENT THERAPY:

• At least 4 weeks since prior pemetrexed disodium-containing chemotherapy
• At least 4 weeks since prior major surgery
• At least 4 weeks since prior radiation therapy
• Measurable disease must be outside the radiation port
• Prior intracavitary cytotoxic or sclerosing therapy (including bleomycin) allowed
• Intrapleural cytotoxic chemotherapy will not be considered systemic chemotherapy
• No prior tyrosine kinase, signal transduction, or angiogenesis inhibitor therapy
• At least 7 days since prior and no concurrent antithrombotic or anti-platelet agents, including any of the following:
• Aspirin or aspirin-containing combinations
• Clopidogrel
• Dipyridamole
• Tirofiban
• Epoprostenol
• Eptifibatide
• Cilostazol
• Abciximab
• Ticlopidine
• Warfarin
• Low-dose warfarin for prophylaxis to prevent catheter thrombosis allowed
• Heparin or low molecular weight heparin
• Heparin for IV line flush allowed
• At least 7 days since prior and no concurrent use of the following drugs:
• Itraconazole
• Ketoconazole (at doses > 200 mg/day)
• Miconazole
• Voriconazole
• Telithromycin
• Primidone
• Rifabutin
• Rifampin
• St. John’s wort
• Carbamazepine
• Oxcarbazepine
• Rifapentine
• Phenobarbital
• Phenytoin
• Quinidine
• Procainamide
• Disopyramide
• Amiodarone
• Sotalol
• Ibutilide
• Dofetilide
• Erythromycin
• Clarithromycin
• Chlorpromazine
• Haloperidol
• Mesoridazine
• Thioridazine
• Pimozide
• Bepridil
• Droperidol
• Halofantrine
• Levomethadyl
• Sparfloxacin
• No concurrent H2 blockers or proton pump inhibitors
• No bisphosphonate therapy during the first 8 weeks of study treatment
• No concurrent hormones or other chemotherapeutic agents except for steroids administered for dasatinib-related pleural effusion or hormones administered for non-disease-related conditions (e.g., insulin for diabetes)
• No concurrent palliative radiation therapy

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Cancer and Leukemia Group B

CCOP – Christiana Care Health Services

Newark Delaware 19713 United States

Tunnell Cancer Center at Beebe Medical Center

Lewes Delaware 19958 United States

Lombardi Comprehensive Cancer Center at Georgetown University Medical Center

Washington District of Columbia 20007 United States

Florida Hospital Cancer Institute at Florida Hospital Orlando

Orlando Florida 32803-1273 United States

University of Chicago Cancer Research Center

Chicago Illinois 60637-1470 United States

Fort Wayne Medical Oncology and Hematology

Fort Wayne Indiana 46815 United States

Harry & Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center

Baltimore Maryland 21237 United States

Union Hospital Cancer Program at Union Hospital

Elkton MD Maryland 21921 United States

Arch Medical Services, Incorporated at Center for Cancer Care and Research

Saint Louis Missouri 63141 United States

Missouri Baptist Cancer Center

St. Louis Missouri 63131 United States

Methodist Estabrook Cancer Center

Omaha Nebraska 68114 United States

Cancer Institute of New Jersey at Cooper – Voorhees

Voorhees New Jersey 08043 United States

SUNY Upstate Medical University Hospital

Syracuse New York 13210 United States

Kinston Medical Specialists

Kinston North Carolina 28501 United States

Wayne Memorial Hospital, Incorporated

Goldsboro North Carolina 27534 United States

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Columbus Ohio 43210-1240 United States

Danville Regional Medical Center

Danville Virginia 24541 United States

Overall Clinical Trial Officials and Contacts

Arkadiusz Dudek, MD Study Chair University of Minnesota

Additional Information

Information obtained from ClinicalTrials.gov on April 01, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00509041

Study ID Number: CDR0000558362

ClinicalTrials.gov Identifier: NCT00509041

Health Authority: Unspecified

href=”http://www.cancer.gov/clinicaltrials/CALGB-30601″>Clinical trial summary from the National Cancer Institute’s PDQ® database

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

posted by Your Attorney at 12:01 AM
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Pharmacokinetic, Safety, and Efficacy Effects of Oral LBH589 on Dextromethorphan in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer or

Date First Received: September 26, 2007
Last Updated: September 26, 2007
Verified by: Novartis, September 2007
Clinical Trial Phase: Phase 1 Start Date: September 2007
Overall Status: Recruiting
Estimated Enrollment: 24

Brief Summary

Official Title: “A Phase IB, Open-Label, Multicenter Study to Investigate the Effect of Oral LBH589 on Dextromethorphan, a CYP2D6 Substrate, and to Assess the Efficacy and Safety of Oral LBH589 in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) or Malignant Pleural Mesothelioma”

This study will investigate the effect of oral LBH589 on dextromethorphan, a CYP2D6 substrate, and to assess safety and efficacy of oral LBH589 when used with this co-medication in advanced stage NSCLC or malignant pleural mesothelioma patients

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study

Outcome Measures for this Clinical Trial

Primary:

• Pharmacokinetic (PK) parameters Safety and tolerability (days 1-10) assessed by AEs, SAEs, labs, ECG reports, radiology reports.

Secondary:

• Response rate assessed by comparing tumor size via radiology scans (CTs or MRIs) Safety and tolerability (until disease progression, unacceptable toxicity or study completion) assessed by duration of patient participation

Criteria for Participation in this Clinical Trial

Inclusion criteria

• Age ≥ 18 years
• At time of diagnosis or relapse, histologically confirmed NSCLC with locally advanced or metastatic disease (stage IIIA, IIIB, or IV) or histologically confirmed mesothelioma of the pleura which is unresectable
• Must have failed prior standard systemic therapy NSCLC patients must have failed at least two prior therapies, including a platinum-based chemotherapy regimen Malignant Pleural Mesothelioma patients must have failed at least one pemetrexed- or cisplatin-based chemotherapy regimen
• Must have measurable disease (by computerized tomography [CT] or magnetic resonance imaging [MRI]) per disease specific criteria (RECIST criteria for NSCLC and modified RECIST criteria for mesothelioma)
• Mesothelioma patients may have undergone pleurodesis
• Written informed consent obtained prior to any screening procedures
• Willingness to have multiple blood draws
• Ability to swallow capsules or tablets

Exclusion criteria

• Known brain metastases
• Prior treatment with an HDAC inhibitor
• Presence of clinically detectable third-space fluid collections (e.g., ascites or pleural effusions) that can be controlled by drainage or other procedures prior to study entry
• Concomitant use of any anti-cancer therapy, including radiation therapy
• Significant cardiac disease
• Concomitant use of drugs with a risk of causing torsades de pointes
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LBH589
• Previous use of monoamine oxidase inhibitors (e.g. clorgyline, iproniazid, isocarboxazid, moclobemide, sibutramine, phenelzine, tranylcypromine) within 14 days prior to the first dose of dextromethorphan

Other protocol-defined inclusion/exclusion criteria may apply

Clinical Trials Locations, Contact Details, and Sponsors

Lead Sponsor: Novartis
RUSH Medical Center
Chicago Illinois United States
MD Anderson Cancer Center
Houston Texas United States
Ontario Canada

Overall Clinical Trial Officials and Contacts

Novartis Study Chair Novartis
Overall Contact: Novartis U.S. 800 340 6843

Additional Information

Information obtained from ClinicalTrials.gov on April 01, 2008
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00535951
Study ID Number: CLBH589B2109
ClinicalTrials.gov Identifier: NCT00535951
Health Authority: Canada: Health Canada (Sante Canada)

Clinical Trials Authorship and Review

Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

Labels: ClinicalTrial

posted by Your Attorney at 12:00 AM
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