Pemetrexed, Cisplatin, and Vitamin B12 in Treating Patients With Mesothelioma of the Chest That Cannot Be Removed by Surgery

NCT ID: NCT00541073

Last Updated: 2011-05-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-06-30

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.

Conditions

Malignant Mesothelioma

Study Design

• Allocation Method: NON_RANDOMIZED
• Primary Study Purpose: TREATMENT

Interventions

vitamin B12

Intervention Type: DIETARY_SUPPLEMENT

cisplatin

Intervention Type: DRUG

pemetrexed disodium

Intervention Type: DRUG

gene expression analysis

Intervention Type: GENETIC

laboratory biomarker analysis

Intervention Type: OTHER

pharmacological study

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed pleural mesothelioma

• Unresectable disease

• 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

• At least 28 days since prior radiotherapy (21 days for injected radiotherapy)

Exclusion Criteria

• Clinically detected pleural effusion or ascites that cannot be controlled by drainage or other procedures

PATIENT CHARACTERISTICS:

• 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:

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Oscar Lambret

OTHER

Sponsor Role: lead

Principal Investigators

Amelie Lansiaux, MD, PhD

Role:

Centre Oscar Lambret

Locations

Centre Oscar Lambret

Lille, , France

Countries

France

Other Identifiers

COL-ALIMESO

Identifier Type: -

Identifier Source: secondary_id

INCA-RECF0441

Identifier Type: -

Identifier Source: secondary_id

COL-2006-04

Identifier Type: -

Identifier Source: secondary_id

CDR0000564058

Identifier Type: -

Identifier Source: org_study_id