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

May 14, 2011 updated by: Centre Oscar Lambret

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 Overview

Status

Completed

Conditions

Malignant Mesothelioma

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

Phase

Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

France
- - Lille, France, 59020
    - Centre Oscar Lambret

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: TREATMENT
Allocation: NON_RANDOMIZED

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Individual dosage-adapted protocol

Secondary Outcome Measures

Outcome Measure
Pharmacokinetics
Relationship between pharmacokinetic and pharmacodynamic parameters
Pharmacogenetic variations (MTHFR, TS, GSTpi, ERCC1, XPD)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Oscar Lambret

Investigators

Amelie Lansiaux, MD, PhD, Centre Oscar Lambret

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2007

Primary Completion (ACTUAL)

May 1, 2011

Study Registration Dates

First Submitted

October 5, 2007

First Submitted That Met QC Criteria

October 5, 2007

First Posted (ESTIMATE)

October 8, 2007

Study Record Updates

Last Update Posted (ESTIMATE)

May 17, 2011

Last Update Submitted That Met QC Criteria

May 14, 2011

Last Verified

July 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

CDR0000564058
COL-ALIMESO
INCA-RECF0441
COL-2006-04

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.