Official Title: “Phase 2 Pharmacological Study of Pemetrexed Administered With Cisplatin and a Vitamin Supplement in Patients With Nonresectable Pleural Mesothelioma”

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.

Study Type: Interventional

Study Design: Treatment, Non-Randomized

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.

Intervention(s) in this Clinical Trial

• Dietary Supplement: vitamin B12
• Drug: cisplatin
• Drug: pemetrexed disodium
• Genetic: gene expression analysis
• Other: laboratory biomarker analysis
• Other: pharmacological study

Primary Measures

• Individual dosage-adapted protocol
  • Safety Issue?: No

Secondary Measures

• Relationship between pharmacokinetic and pharmacodynamic parameters
  • Safety Issue?: No
• Pharmacokinetics
  • Safety Issue?: No
• Pharmacogenetic variations (MTHFR, TS, GSTpi, ERCC1, XPD)
  • Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Centre Oscar Lambret

Overall Clinical Trial Officials and Contacts

Amelie Lansiaux, MD, PhD  Centre Oscar Lambret  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00541073

Study ID Number: CDR0000564058

ClinicalTrials.gov Identifier: NCT00541073

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database