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

Malignant Mesothelioma Clinical Trial

Official title:

Phase 2 Pharmacological Study of Pemetrexed Administered With Cisplatin and a Vitamin Supplement in Patients With Nonresectable Pleural Mesothelioma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00541073
• Other study ID #: CDR0000564058
• Secondary ID: COL-ALIMESOINCA-
• Status: Completed
• Phase: Phase 2
• First received: October 5, 2007
• Last updated: May 14, 2011
• Start date: June 2007

Study information

• Verified date: July 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lung Neoplasms
• Malignant Mesothelioma
• Mesothelioma

Intervention

Dietary Supplement:
• vitamin B12

Drug:
• cisplatin

• pemetrexed disodium

Genetic:
• gene expression analysis

Other:
• laboratory biomarker analysis

• pharmacological study

Locations

Country	Name	City	State
France	Centre Oscar Lambret	Lille

Sponsors (1)

Lead Sponsor	Collaborator
Centre Oscar Lambret

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Individual dosage-adapted protocol			No
Secondary	Relationship between pharmacokinetic and pharmacodynamic parameters			No
Secondary	Pharmacokinetics			No
Secondary	Pharmacogenetic variations (MTHFR, TS, GSTpi, ERCC1, XPD)			No