Saturday, March 1, 2008

Extrapleural Pneumonectomy, IHOC Cisplatin and Gemcitabine With Amifostine and Sodium Thiosulfate Cytoprotection for Resectable Malignant Pleural Meso
Extrapleural Pneumonectomy, IHOC Cisplatin and Gemcitabine With Amifostine and Sodium Thiosulfate Cytoprotection for Resectable Malignant Pleural Mesothelioma

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: “A 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
Intervention(s):
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.

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
Criteria for Participation in this Clinical Trial

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 15, 2008
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00571298
Study ID Number: 07-091
ClinicalTrials.gov Identifier: NCT00571298
Health Authority: United States: Institutional Review Board
International Mesothelioma Program
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

A Phase II Study of the Association of Glivec® Plus Gemzar® in Patients With Unresectable, Refractory, Malignant Mesothelioma

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...

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”

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

Study Type: Interventional

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

Detailed Clinical Trial Description

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"

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

Criteria for Participation in this Clinical Trial

Inclusion Criteria:

• Age of > 18 years and <>
• Patients with a histologically proven malignant mesothelioma of the pleura or of the peritoneum, expressing either PDFGR-beta or C-Kit by immunochemistry (ICH)
• Locally advanced disease, unsuitable for curative surgical resection, or metastatic disease
• Confirmed progression of the disease according to modified REcist-criteria, documented after a first-line, systemic (premetrex+cisplatin regimen) or local treatment (i.e., intrapleuric)
• ECOG Performance Status of 0, 1 or 2
• Life expectancy of at least 3 months
• Capability of understanding the objectives of the study and giving written informed consent
• Willingness and ability to comply with study requirements
• Sufficient caloric and fluid intake, including patients under enteral or parenteral nutrition

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 <>
• WBC <>
• Neutrophils <>
• Platelets <>
• Serum bilirubin > 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

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

Related Publications

References

Bertino P, Porta C, Barbone D, Germano S, Busacca S, Pinato S, Tassi G, Favoni R, Gaudino G, Mutti L. Preliminary data suggestive of a novel translational approach to mesothelioma treatment: imatinib mesylate with gemcitabine or pemetrexed. Thorax. 2007 Aug;62(8):690-5. Epub 2007 Feb 20.

Additional Information

Information obtained from ClinicalTrials.gov on April 15, 2008

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

Study ID Number: GIMe/01/06

ClinicalTrials.gov Identifier: NCT00551252

Health Authority: Italy: Ethics Committee

Italian Mesothelioma Group Homepage

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

Phase II Study of Bevacizumab, Pemetrexed and Carboplatin as First-Line Therapy in Malignant Pleural Mesothelioma

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

Date First Received: December 4, 2006

Last Updated: August 28, 2007

Verified by: Istituto Clinico Humanitas, August 2007

Clinical Trial Phase: Phase 2 Start Date:

Overall Status: Not yet recruiting

Estimated Enrollment: 77

Brief Summary

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

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

Study Type: Interventional

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

Detailed Clinical Trial Description

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.

Criteria for Participation in this Clinical Trial

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

Related Publications

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

Health Authority: Italy: 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

A Study of VEGF-Antisense Oligonucleotide in Combination With Pemetrexed and Cisplatin for the Treatment of Advanced Malignant Mesothelioma

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...

Date First Received: April 25, 2008
Last Updated: April 28, 2008
Verified by: Norris Comprehensive Cancer Center, April 2008
Clinical Trial Phase: Phase 1/Phase 2 | Start Date: April 2008
Overall Status: Not yet recruiting
Estimated Enrollment: 71
Brief Summary
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
Intervention(s):
• 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
Criteria for Participation in this Clinical Trial
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 as defined below:
• 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
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

Mesothelioma Avastin Plus Pemetrexed-Cisplatin Study

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...

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)”
Condition Keyword(s):
• Mesothelioma
Intervention(s):
• 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
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 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
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

Extrapleural Pneumonectomy, IHOC Cisplatin and Gemcitabine With Amifostine and Sodium Thiosulfate Cytoprotection for Resectable Malignant Pleural Mesothelioma

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: “A 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
Intervention(s):
• 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.
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
Criteria for Participation in this Clinical Trial
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
Health Authority: United States: Institutional Review Board
International Mesothelioma Program
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

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

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...

Date First Received: November 9, 2006
Last Updated: April 1, 2008
Verified by: National Cancer Institute (NCI), March 2008
Clinical Trial Phase: Phase 1 | Start Date: October 2006
Overall Status: Recruiting
Estimated Enrollment: 20
Brief Summary
Official Title: “Pilot Trial of a WT-1 Analog Peptide Vaccine in Patients With Thoracic and Myeloid Neoplasms”
Condition Keyword(s):
• Leukemia
• Lung Cancer
• Malignant Mesothelioma
• Myelodysplastic Syndromes
• Peritoneal Cavity Cancer
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
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.
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
Criteria for Participation in this Clinical Trial
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
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

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

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...

Date First Received: September 12, 2005

Last Updated: February 11, 2008

Verified by: Eli Lilly and Company, February 2008

Clinical Trial Phase: Phase 2 | Start Date: June 2005

Overall Status: Recruiting

Estimated Enrollment: 53

Brief Summary

Official Title: “Phase II Trial of Neoadjuvant ALIMTA Plus Cisplatin Followed by Surgery and Radiation in the Treatment of Pleural Mesothelioma”

Condition Keyword(s):

• Mesothelioma

Intervention(s):

• 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

Criteria for Participation in this Clinical Trial

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.

Mestre/Venezia 30170 Italy

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.

Milano 20141 Italy

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.

Padova 35100 Italy

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.

Rome 00128 Italy

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.

Napoli 80131 Italy

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

Health Authority: Italy: Ministry of Health

Lilly Clinical Trial Registry

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

Decitabine and FR901228 in Treating Patients With Advanced Lung Cancer, Esophageal Cancer, Pleural Mesothelioma, or Lung Metastases

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...

Date First Received: July 8, 2002
Last Updated: December 25, 2007
Verified by: National Cancer Institute (NCI), September 2007
Clinical Trial Phase: Phase 1 | Start Date: May 2002
Overall Status: Recruiting
Estimated Enrollment: 40
Brief Summary
Official Title: “Phase I Study of Gene Induction Mediated by Sequential Decitabine/Depsipeptide Infusion in Subjects With Pulmonary and Pleural Malignancies”
Condition Keyword(s):
• Esophageal Cancer
• Lung Cancer
• Malignant Mesothelioma
• Metastatic Cancer
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
Detailed Clinical Trial Description
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.
Criteria for Participation in this Clinical Trial
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) by
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
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.

Labels: ClinicalTrial

Study of Pemetrexed in Mesothelioma and Lung Cancer Patients With Fluid Around the Lungs or Abdomen

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

Date First Received: April 18, 2006
Last Updated: January 21, 2008
Verified by: Eli Lilly and Company, January 2008
Clinical Trial Phase: Phase 2 | Start Date: December 2006
Overall Status: Recruiting
Estimated Enrollment: 30
Brief Summary
Official Title: “A Phase 2 Study of ALIMTA in Solid Tumor Patients With Stable Third-Space Fluid”
Condition Keyword(s):
• Non-Small Cell Lung Cancer
• Mesothelioma
• Lung Neoplasms
Intervention(s):
• Drug: pemetrexed
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
Criteria for Participation in this Clinical Trial
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
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.
Odense 5000 Denmark
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.
Hannover D-30625 Germany
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.
Madrid 28041 Spain
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
Health Authority: United States: Food and Drug Administration
Lilly Clinical Trial Registry
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

Phase I Dose-Escalation Study Of Azacitidine In Combination With Temozolomide

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...

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
Brief Summary

Official Title: “A Phase I Dose-Escalation Study Of Azacitidine In Combination With Temozolomide In Patients With Unresectable Or Metastatic Soft Tissue Sarcoma or Malignant Mesothelioma”

Condition Keyword(s):

* Soft Tissue Sarcoma
* Mesothelioma

Intervention(s):

* Drug: Azacitidine In Combination With Temozolomide

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
Detailed Clinical Trial Description

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

Criteria for Participation in this Clinical Trial

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 < 1.5 times upper limit of normal (ULN) for the laboratory.
* Transaminases: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels must be < 2 x ULN. If there is known hepatic metastasis, transaminases may be < 5 times upper limit of normal.
* Serum creatinine levels < 1.5 x ULN.
* 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

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

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
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

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