Biomarkers in Predicting Neurotoxicity in Patients With Colorectal Cancer Receiving Oxaliplatin

Institut Cancerologie de l'Ouest

Status and phase: Unknown; Phase 2

Conditions: Chemotherapeutic Agent Toxicity; Neurotoxicity; Colorectal Cancer

Treatments: Other: laboratory biomarker analysis; Other: pharmacogenomic studies; Drug: leucovorin calcium; Genetic: proteomic profiling; Drug: fluorouracil; Genetic: gene expression analysis; Drug: oxaliplatin; Drug: FOLFOX regimen; Genetic: protein expression analysis

Study type: Interventional

Funder types: Other

Identifiers

NCT00884767

EUDRACT-2007-001287-75

CPP-CPP340

CPP-NEUROTOXALI

CDR0000633477

INCA-RECF0453

Details and patient eligibility

About

RATIONALE: Studying samples of blood in the laboratory from patients receiving oxaliplatin for cancer may help doctors learn more about changes that occur in DNA and identify biomarkers related to neurotoxicity.

PURPOSE: This phase II trial is studying biomarkers in predicting neurotoxicity in patients with colorectal cancer receiving oxaliplatin.

Full description

OBJECTIVES:

Primary

• Correlate predictive genetic, proteomic, and/or neurotrophic markers with neurological manifestations related to the administration of oxaliplatin in patients with colorectal carcinoma.

Secondary

• Differentiate between risk factors predictive of acute and chronic neurotoxicity.
• Establish a possible relationship between acute and chronic neurotoxicity.

OUTLINE: This is a multicenter study.

Patients receive oxaliplatin every 2 weeks as part of a FOLFOX chemotherapy regimen.

Blood samples are collected 15 days prior to beginning chemotherapy, prior to each course of chemotherapy, and at 1 month after completion of chemotherapy for pharmacogenetic and laboratory biological studies. Patients with chronic neurotoxicity undergo additional blood sample collection at 3, 6, 9, and 12 months after completion of chemotherapy. Samples are analyzed for the detection of gene variants involved in the oxalate and fluorouracil metabolic pathway; neurotrophic factors; proteomic analysis of plasma proteins and peptides; and for biological testing of neurotoxicity.

Enrollment: 206 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal cancer
• Requires treatment with oxaliplatin (as part of a FOLFOX regimen)
• No brain metastases or symptomatic meningitis

PATIENT CHARACTERISTICS:

• WHO performance status 0-2
• Life expectancy > 3 months
• ANC ≥ 1 x 10^9/L
• Platelet count ≥ 100 x 10^9/L
• Total bilirubin ≤ 2 times upper limit of normal (ULN)
• Transaminases ≤ 3 times ULN
• Alkaline phosphatase ≤ 5 times ULN
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No prior or concurrent clinical neuropathy (regardless of the etiology)
• No dihydropyrimidine dehydrogenase deficiency
• No psychiatric illness that would preclude comprehension of the study or of the informed consent
• No other severe illness that may worsen during treatment, including unstable cardiac disease, myocardial infarction within the past 6 months, or active uncontrolled infection
• No psychological, social, familial, or geographical reason that would preclude study follow-up
• Other cancer within the past 5 years allowed provided treatment did not include platinum derivatives or taxanes

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Prior chemotherapy allowed (except for platinum derivatives or taxanes)