Clinical trial NCT00884767: Biomarkers in Predicting Neurotoxicity in Patients With Colorectal Cancer Receiving Oxaliplatin
Official title: Characterization and Research of Predictive Markers of Neurotoxicity During Treatment With Oxaliplatin in Colorectal Carcinoma: a Genetic and Proteomic Approach. Phase II Multicenter Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Chemotherapeutic Agent Toxicity
Colorectal Cancer
Neurotoxicity
Keywords: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2009-04-21
Enrollment: 206
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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)

Primary outcomes:
measure: Correlation of genetic profiles and peptide, protein, and neurotrophic factors with neurological toxicity
Secondary outcomes:
Other outcomes:
Locations:
city: Angers
country: France
facility: Centre Paul Papin
Study officials:
affiliation: Institut Cancerologie de l'Ouest
name: Erick Gamelin, MD
role: PRINCIPAL_INVESTIGATOR
References: