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

Sponsor:	Centre Oscar Lambret
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00541073

Purpose

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	Intervention	Phase
Malignant Mesothelioma	Dietary Supplement: vitamin B12 Drug: cisplatin Drug: pemetrexed disodium Genetic: gene expression analysis Other: laboratory biomarker analysis Other: pharmacological study	Phase II

Study Type:	Interventional
Study Design:	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

Resource links provided by NLM:

MedlinePlus related topics: B Vitamins Cancer Dietary Supplements Mesothelioma

Drug Information available for: Vitamin B 12 Hydroxocobalamin Cisplatin Pemetrexed Pemetrexed disodium

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Individual dosage-adapted protocol [ Designated as safety issue: No ]

Secondary Outcome Measures:

Relationship between pharmacokinetic and pharmacodynamic parameters [ Designated as safety issue: No ]
Pharmacokinetics [ Designated as safety issue: No ]
Pharmacogenetic variations (MTHFR, TS, GSTpi, ERCC1, XPD) [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	June 2007
Primary Completion Date:	May 2011 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00541073

Locations

France
Centre Oscar Lambret
Lille, France, 59020

Sponsors and Collaborators

Centre Oscar Lambret

Investigators

Investigator:

Amelie Lansiaux, MD, PhD

Centre Oscar Lambret

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

ClinicalTrials.gov Identifier:	NCT00541073 History of Changes
Other Study ID Numbers:	CDR0000564058, COL-ALIMESO, INCA-RECF0441, COL-2006-04
Study First Received:	October 5, 2007
Last Updated:	May 14, 2011
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

advanced malignant mesothelioma
recurrent malignant mesothelioma

Additional relevant MeSH terms:

Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial
Pemetrexed
Cisplatin
Vitamin B 12
Hydroxocobalamin
Vitamin B Complex
Vitamins
Antineoplastic Agents

Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Micronutrients
Growth Substances
Hematinics
Hematologic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on February 09, 2012