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.
|First Received Date||October 5, 2007|
|Last Changed Date||May 14, 2011|
|Start Date||June 2007|
|Actual Primary Completion Date||May 2011|
|Primary Outcome Measures||
Individual dosage-adapted protocol
|Secondary Outcome Measures||
Relationship between pharmacokinetic and pharmacodynamic parameters
Pharmacogenetic variations (MTHFR, TS, GSTpi, ERCC1, XPD)
- Define an individually adapted (by dosage) protocol of pemetrexed disodium, cisplatin, and vitamin B12 in patients with unresectable pleural mesothelioma.
- 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.
|Ages||18 Years - N/A|
|Accepts Healthy Volunteers||No|
- Histologically confirmed pleural mesothelioma
- Unresectable disease
- Clinically detected pleural effusion or ascites that cannot be controlled by drainage or other procedures
- 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
- 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:
- At least 28 days since prior radiotherapy (21 days for injected radiotherapy)
- 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
|Sponsor||Centre Oscar Lambret|
|Verification Date||July 2009|