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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00541073
First received: October 5, 2007
Last updated: May 14, 2011
Last verified: July 2009
  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 2

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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
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 July 26, 2014