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Australian Company to Conduct Clinical Trial on Mesothelioma Drug

Thursday, December 10, 2009

Another new mesothelioma drug clinical trial is slated to begin in December 2009. Australian drug maker Bionomics Ltd plans to conduct a Phase II clinical trial of its anti-cancer drug BNC105. They will conduct the tests on 60 mesothelioma patients in Australia.

The drug has shown great promise thus far by killing cancer cells when testing with solid tumors in animals. Bionomics believes patients will not become resistant to this drug as often happens with other chemotherapy treatments. BNC105 will also undergo a Phase II trial in the United States for the treatment of renal cancer.

The primary goal of this study is to determine the safety and maximum tolerated dose of BNC105 in patients with advanced solid tumors. Bionomics says BNC105 “can extend the life of people suffering from mesothelioma and provide them with a better quality of life.”

Sources:
Bionomics Clinical Trials
The Sydney Morning Herald

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Labels: ClinicalTrial, mesothelioma

posted by Nancy Meredith at 7:00 AM
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Clinical Trial Spotlight: Everolimus (RAD001) for the Treatment of Malignant Pleural Mesothelioma

Wednesday, December 9, 2009

Study: Phase II Study of Everolimus (RAD001) for the Treatment of Malignant Pleural Mesothelioma With Merlin/NF2 Loss as a Biomarker to Predict Sensitivity

Start Date: December 2009
End Date: December 2011

Recruiting Contacts:
Contact: Lee Krug, MD (212)639-8420
Contact: Christopher Azzoli, MD (212)639-2131

Information:
Memorial Sloan-Kettering Cancer Center is conducting a clinical trial for patients with a confirmed diagnosis of epithelioid, sarcomatoid, or mixed-type malignant pleural mesothelioma that is not amenable to surgery for treatment with everolimus.

The purpose of this study is to find out what effects, both good and bad, that everolimus has on the cancer. Everolimus works by blocking a protein that helps the cancer grow. The goal of this clinical research study is to learn if the study drug everolimus can shrink or slow the growth of mesothelioma.

The enrollment goal for this study is 39 participants. At the end of the study, if 17 or more patients show clinical benefit out of a total of 39 patients enrolled, the regimen will be considered worthy of further investigation.

For complete information see ClinicalTrials.

© MesotheliomaHelp.Net. All Rights Reserved. Reprinting or republication of this article or any portion of its content is permitted but must include the MesotheliomaHelp.Net link.

Labels: ClinicalTrial, mesothelioma

posted by Nancy Meredith at 8:00 AM
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Lung Cancer Clinical Trial Matching Service

Thursday, November 26, 2009

As part of the Lung Cancer Clinical Trials Call to Action Campaign , Lung Cancer Alliance, National Lung Cancer Partnership, and other advocacy groups have partnered with EmergingMed to offer a personalized service for lung cancer patients “to take charge of their diagnosis and learn about clinical trials, which are an important part of treatment innovation.”

The initiative matches lung cancer patients with currently recruiting clinical trials based on the patient’s diagnosis. After building a profile covering areas such as activity level, level of cancer metastasis, type of cancer such as mesothelioma, treatment regimen, and other conditions, the patient is presented with a list of clinical trials for consideration.

The campaign partners recommend that patients search for clinical trial options prior to the start of their treatment and again when faced with new treatment decisions.

EmergingMed was founded in 2000 with a goal “to increase clinical trial awareness and access through one-on-one, personalized services provided through collaborations with a growing partner network.”

Search for a Clinical Trial

Labels: ClinicalTrial

posted by Nancy Meredith at 2:00 PM
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Clinical Trial Spotlight: Pemetrexed (ALIMTA) Plus Cisplatin for Mesothelioma

Tuesday, October 13, 2009

Study: Pemetrexed (ALIMTA) Plus Cisplatin Followed by Surgery and Radiation Therapy for Mesothelioma

Start Date: January 2009
End Date: January 2020

Recruiting Contacts
Andrea Foster, 416-946-4501 ext 5010, Andrea.Foster@Uhn.on.ca
Jennifer Hornby, BSc CCRP 416-340-4857, Jennifer.Hornby@uhn.on.ca

Information
The University Health Network of Toronto is currently recruiting participants for a clinical trial using a combination of Pemetrexed (Alimta) with Cisplatin prior to surgery followed by radiation therapy after surgery. The goal enrollment for the trial is 45 patients that have been diagnosed with malignant pleural mesothelioma but have not yet undergone treatment.

Previous studies have shown that complete removal of mesothelioma is possible in approximately 30% of the patients, with treatment typically continuing with chemotherapy followed by radiation. The chances of the tumor returning after this trimodal therapy remains high, and the chances of long term survival remains low.

According to the trial information, the combination of Pemetrexed (Alimta) with Cisplatin as chemotherapy treatment is likely to benefit, and potentially cure, a group of patients.

For complete information see ClinicalTrials.

Labels: ClinicalTrial, mesothelioma

posted by Nancy Meredith at 1:07 PM
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Mesothelioma Patients Sought for Clinical Trial

Monday, September 14, 2009

Researchers are seeking 40 patients that have confirmed malignant mesothelioma, who are not candidates for surgery or radiation, to test the drug gefitinib. Gefitinib inhibits cellular growth in cancerous cells by targeting the proteins. The trade name for gefitinib is Iressa.

Malignant mesothelioma is a cancer caused by exposure to airborne asbestos fibers. The fibers are either inhaled or swallowed then travel through the body becoming lodged, resulting in cancer decades later. Often called “asbestos cancer,” mesothelioma is resistant to many current treatments. Currently there is no known cure for mesothelioma, and the average survival time varies from 4 – 18 months after diagnosis.

The study, conducted by researchers at the National Cancer Institute in Bethesda, Maryland, is a Phase II clinical trial to determine the efficacy of the drug for mesothelioma patients. Currently, the drug is used for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC), and who have previously been treated with chemotherapy.

Patients involved in the study will receive daily doses of oral gefitinib while being monitored. Clinicians will follow study participants for up to four years.

Gefitinib Clinical Trial

Labels: ClinicalTrial, mesothelioma, treatments

posted by Nancy Meredith at 1:00 PM
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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

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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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