Biomarkers in Predicting Neurotoxicity in Patients With Colorectal Cancer Receiving Oxaliplatin

Characterization and Research of Predictive Markers of Neurotoxicity During Treatment With Oxaliplatin in Colorectal Carcinoma: a Genetic and Proteomic Approach. Phase II Multicenter Study

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.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer; Neurotoxicity; Chemotherapeutic Agent Toxicity
• Intervention / Treatment: Genetic: gene expression analysis; Drug: fluorouracil; Drug: leucovorin calcium; Genetic: protein expression analysis; Other: laboratory biomarker analysis; Genetic: proteomic profiling; Other: pharmacogenomic studies; Drug: oxaliplatin; Drug: FOLFOX regimen

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 206
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Angers, France, 49036
    • Recruiting
    • Centre Paul Papin
    • Contact: Erick Gamelin, MD; Phone Number: 33-2-4135-2700; Email: e.gamelin@unimedia.fr

Participation Criteria

Eligibility Criteria

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

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Correlation of genetic profiles and peptide, protein, and neurotrophic factors with neurological toxicity

Collaborators and Investigators

• Sponsor: Institut Cancerologie de l'Ouest
• Investigators: Principal Investigator: Erick Gamelin, MD, Institut Cancerologie de l'Ouest

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Anticipated): August 1, 2009

Study Registration Dates

• First Submitted: April 18, 2009
• First Submitted That Met QC Criteria: April 18, 2009
• First Posted (Estimate): April 21, 2009

Study Record Updates

• Last Update Posted (Estimate): July 8, 2009
• Last Update Submitted That Met QC Criteria: July 7, 2009
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Keywords: stage IV rectal cancer; stage IV colon cancer; recurrent colon cancer; recurrent rectal cancer; stage III colon cancer; neurotoxicity; stage II rectal cancer; stage III rectal cancer; stage II colon cancer; stage I rectal cancer; stage I colon cancer; chemotherapeutic agent toxicity
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Poisoning; Colorectal Neoplasms; Neurotoxicity Syndromes; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin; Calcium; Levoleucovorin
• Other Study ID Numbers: CDR0000633477; CPP-NEUROTOXALI; CPP-CPP340; INCA-RECF0453; EUDRACT-2007-001287-75