Pemetrexed, Cisplatin, and Vitamin B12 in Treating Patients With Mesothelioma of the Chest That Cannot Be Removed by Surgery
Primary Purpose
Malignant Mesothelioma
Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
vitamin B12
cisplatin
pemetrexed disodium
gene expression analysis
laboratory biomarker analysis
pharmacological study
Sponsored by
About this trial
This is an interventional treatment trial for Malignant Mesothelioma focused on measuring advanced malignant mesothelioma, recurrent malignant mesothelioma
Eligibility Criteria
DISEASE CHARACTERISTICS:
Inclusion criteria:
Histologically confirmed pleural mesothelioma
- Unresectable disease
Exclusion criteria:
- Clinically detected pleural effusion or ascites that cannot be controlled by drainage or other procedures
PATIENT CHARACTERISTICS:
Inclusion criteria:
- WHO performance status 0-2
- Life expectancy > 3 months
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Creatinine clearance > 45 mL/min
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- Transaminases ≤ 3 times ULN (5 times ULN if liver metastases)
- Not pregnant or nursing
- Fertile patients of must use effective contraception during and for 6 months after completion of study treatment
Exclusion criteria:
- Hypersensitivity to pemetrexed disodium or any of its excipients
- Peripheral neuropathy ≥ grade 2
- Impossible to receive study therapy due to geographical, social, familial, or psychological reasons
PRIOR CONCURRENT THERAPY:
Inclusion criteria:
- At least 28 days since prior radiotherapy (21 days for injected radiotherapy)
Exclusion criteria:
- Prior chemotherapy
- Prior yellow fever vaccine
- Inability to discontinue aspirin (> 1.3 g/day) or NSAIDs for 2 days prior to, during, and 2 days after day 1 of each course of study therapy
- Concurrent participation in another clinical study
Sites / Locations
- Centre Oscar Lambret
Outcomes
Primary Outcome Measures
Individual dosage-adapted protocol
Secondary Outcome Measures
Relationship between pharmacokinetic and pharmacodynamic parameters
Pharmacokinetics
Pharmacogenetic variations (MTHFR, TS, GSTpi, ERCC1, XPD)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00541073
Brief Title
Pemetrexed, Cisplatin, and Vitamin B12 in Treating Patients With Mesothelioma of the Chest That Cannot Be Removed by Surgery
Official Title
Phase 2 Pharmacological Study of Pemetrexed Administered With Cisplatin and a Vitamin Supplement in Patients With Nonresectable Pleural Mesothelioma
Study Type
Interventional
2. Study Status
Record Verification Date
July 2009
Overall Recruitment Status
Completed
Study Start Date
June 2007 (undefined)
Primary Completion Date
May 2011 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
Centre Oscar Lambret
4. Oversight
5. Study Description
Brief Summary
RATIONALE: Pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving pemetrexed together with cisplatin and vitamin B12 may kill more tumor cells.
PURPOSE: This phase II clinical trial is studying how well giving pemetrexed together with cisplatin and vitamin B12 works in treating patients with mesothelioma of the chest that cannot be removed by surgery.
Detailed Description
OBJECTIVES:
Primary
Define an individually adapted (by dosage) protocol of pemetrexed disodium, cisplatin, and vitamin B12 in patients with unresectable pleural mesothelioma.
Secondary
Determine the relationship between pharmacokinetic and pharmacodynamic parameters (hematologic and nonhematologic).
Analyze the inter-individual pharmacokinetic variations and the influence of the covariables on the pharmacokinetics of pemetrexed disodium.
Analyze the impact of pharmacogenetic (MTHFR, TS, GSTpi, ERCC1, XPD) variations on the toxicity of pemetrexed disodium.
Validate a strategy of adapting dosage.
OUTLINE: This is a multicenter study.
Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive vitamin B12 intramuscularly on day -7 and then every 9 weeks until chemotherapy is completed.
Blood samples are collected during the first and third courses of chemotherapy. Samples are analyzed by pharmacogenetic (MTHFR, TS, GSTpi, ERCC1, xPD), pharmacokinetic, and other pharmacological methods.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Mesothelioma
Keywords
advanced malignant mesothelioma, recurrent malignant mesothelioma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Allocation
Non-Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Intervention Type
Dietary Supplement
Intervention Name(s)
vitamin B12
Intervention Type
Drug
Intervention Name(s)
cisplatin
Intervention Type
Drug
Intervention Name(s)
pemetrexed disodium
Intervention Type
Genetic
Intervention Name(s)
gene expression analysis
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Type
Other
Intervention Name(s)
pharmacological study
Primary Outcome Measure Information:
Title
Individual dosage-adapted protocol
Secondary Outcome Measure Information:
Title
Relationship between pharmacokinetic and pharmacodynamic parameters
Title
Pharmacokinetics
Title
Pharmacogenetic variations (MTHFR, TS, GSTpi, ERCC1, XPD)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS:
Inclusion criteria:
Histologically confirmed pleural mesothelioma
Unresectable disease
Exclusion criteria:
Clinically detected pleural effusion or ascites that cannot be controlled by drainage or other procedures
PATIENT CHARACTERISTICS:
Inclusion criteria:
WHO performance status 0-2
Life expectancy > 3 months
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Creatinine clearance > 45 mL/min
Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
Transaminases ≤ 3 times ULN (5 times ULN if liver metastases)
Not pregnant or nursing
Fertile patients of must use effective contraception during and for 6 months after completion of study treatment
Exclusion criteria:
Hypersensitivity to pemetrexed disodium or any of its excipients
Peripheral neuropathy ≥ grade 2
Impossible to receive study therapy due to geographical, social, familial, or psychological reasons
PRIOR CONCURRENT THERAPY:
Inclusion criteria:
At least 28 days since prior radiotherapy (21 days for injected radiotherapy)
Exclusion criteria:
Prior chemotherapy
Prior yellow fever vaccine
Inability to discontinue aspirin (> 1.3 g/day) or NSAIDs for 2 days prior to, during, and 2 days after day 1 of each course of study therapy
Concurrent participation in another clinical study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amelie Lansiaux, MD, PhD
Organizational Affiliation
Centre Oscar Lambret
Facility Information:
Facility Name
Centre Oscar Lambret
City
Lille
ZIP/Postal Code
59020
Country
France
12. IPD Sharing Statement
Learn more about this trial
Pemetrexed, Cisplatin, and Vitamin B12 in Treating Patients With Mesothelioma of the Chest That Cannot Be Removed by Surgery
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