Malignant Mesothelioma
Conditions
Keywords
advanced malignant mesothelioma, recurrent malignant mesothelioma
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.
Interventions
DIETARY_SUPPLEMENTvitamin B12
DRUGcisplatin
DRUGpemetrexed disodium
GENETICgene expression analysis
OTHERlaboratory biomarker analysis
OTHERpharmacological study
Sponsors
Centre Oscar Lambret
Study design
Allocation
NON_RANDOMIZED
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Individual dosage-adapted protocol | — |
Secondary
| Measure | Time frame |
|---|---|
| Relationship between pharmacokinetic and pharmacodynamic parameters | — |
| Pharmacokinetics | — |
| Pharmacogenetic variations (MTHFR, TS, GSTpi, ERCC1, XPD) | — |
Countries
France
Contacts
Overall OfficialAmelie Lansiaux, MD, PhD
Centre Oscar Lambret
Outcome results
None listed