Clinical trial NCT00541073: Pemetrexed, Cisplatin, and Vitamin B12 in Treating Patients With Mesothelioma of the Chest That Cannot Be Removed by Surgery
Official title: Phase 2 Pharmacological Study of Pemetrexed Administered With Cisplatin and a Vitamin Supplement in Patients With Nonresectable Pleural Mesothelioma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malignant Mesothelioma
Keywords: advanced malignant mesothelioma
recurrent malignant mesothelioma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-10-08
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Individual dosage-adapted protocol
Secondary outcomes:
measure: Relationship between pharmacokinetic and pharmacodynamic parameters
measure: Pharmacokinetics
measure: Pharmacogenetic variations (MTHFR, TS, GSTpi, ERCC1, XPD)
Other outcomes:
Locations:
city: Lille
country: France
facility: Centre Oscar Lambret
Study officials:
affiliation: Centre Oscar Lambret
name: Amelie Lansiaux, MD, PhD
References: