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

• ClinicalTrials.gov Identifier: NCT00541073
• Recruitment Status: Completed
• First Posted: October 8, 2007
• Last Update Posted: May 17, 2011
• Sponsor: Centre Oscar Lambret
• Information provided by: National Cancer Institute (NCI)

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Malignant Mesothelioma	Dietary Supplement: vitamin B12; Drug: cisplatin; Drug: pemetrexed disodium; Genetic: gene expression analysis; Other: laboratory biomarker analysis; Other: pharmacological study	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Non-Randomized
• Primary Purpose: Treatment
• Official Title: Phase 2 Pharmacological Study of Pemetrexed Administered With Cisplatin and a Vitamin Supplement in Patients With Nonresectable Pleural Mesothelioma
• Study Start Date: June 2007
• Actual Primary Completion Date: May 2011

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

1. Individual dosage-adapted protocol

Secondary Outcome Measures :

1. Relationship between pharmacokinetic and pharmacodynamic parameters
2. Pharmacokinetics
3. Pharmacogenetic variations (MTHFR, TS, GSTpi, ERCC1, XPD)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

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

Contacts and Locations

Locations

France

Centre Oscar Lambret

Lille, France, 59020

Sponsors and Collaborators

Centre Oscar Lambret

Investigators

• OverallOfficial: Amelie Lansiaux, MD, PhD; Centre Oscar Lambret

More Information

• ClinicalTrials.gov Identifier: NCT00541073
• Other Study ID Numbers: CDR0000564058; COL-ALIMESO; INCA-RECF0441; COL-2006-04
• First Posted: October 8, 2007
• Last Update Posted: May 17, 2011
• Last Verified: July 2009

Keywords provided by National Cancer Institute (NCI):

advanced malignant mesothelioma; recurrent malignant mesothelioma

Additional relevant MeSH terms:

Mesothelioma; Mesothelioma, Malignant; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases; Vitamin B 12; Hydroxocobalamin; Pemetrexed; Vitamins; Micronutrients; Physiological Effects of Drugs; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Vitamin B Complex; Hematinics