Biomarkers in Predicting Neurotoxicity in Patients With Colorectal Cancer Receiving Oxaliplatin

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Chemotherapeutic Agent Toxicity, Colorectal Cancer, Neurotoxicity

Intervention / Treatment
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* Drug: FOLFOX regimen
* Drug: fluorouracil
* Drug: leucovorin calcium
* Drug: oxaliplatin
* Genetic: gene expression analysis
* Genetic: protein expression analysis
* Genetic: proteomic profiling
* Other: laboratory biomarker analysis
* Other: pharmacogenomic studies


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: FOLFOX regimen|nan|
|Drug: fluorouracil|nan|
|Drug: leucovorin calcium|nan|
|Drug: oxaliplatin|nan|
|Genetic: gene expression analysis|nan|
|Genetic: protein expression analysis|nan|
|Genetic: proteomic profiling|nan|
|Other: laboratory biomarker analysis|nan|
|Other: pharmacogenomic studies|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of genetic profiles and peptide, protein, and neurotrophic factors with neurological toxicity |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neurotoxicity, chemotherapeutic agent toxicity, recurrent colon cancer, stage I colon cancer, stage II colon cancer, stage III colon cancer, stage IV colon cancer, recurrent rectal cancer, stage I rectal cancer, stage II rectal cancer, stage III rectal cancer, stage IV rectal cancer