Cetuximab and Combination Chemotherapy in Treating Patients With Advanced or Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as irinotecan, fluorouracil, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving cetuximab together with combination chemotherapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving cetuximab together with combination chemotherapy works in treating patients with advanced or metastatic colorectal cancer.

Detailed Description
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OBJECTIVES: Primary Improve hematologic and gastrointestinal tolerance to cetuximab and irinotecan hydrochloride, fluorouracil, and leucovorin calcium (FOLFIRI) in patients with advanced or metastatic colorectal cancer. Secondary Increase the effectiveness of this regimen by intensifying the treatment. Specify the constitutional genetic and genomic tumor parameters that could interfere with and predict the toxicity and/or antitumor efficacy of this regimen. Assess the time to progression. OUTLINE: This is a multicenter study. Patients receive irinotecan hydrochloride IV over 90 minutes, leucovorin calcium IV over 2 hours, and cetuximab IV over 1-2 hours on day 1. Patients also receive fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity. Pharmacokinetic and pharmacogenetic studies are also conducted.

Official Title
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Phase 2 Study to Improve Tolerance of Chemotherapy Involving Cetuximab and Multidrug FOLFIRI, With Pharmacokinetic and Pharmacogenetic Studies, in Patients With Metastatic Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Biological: cetuximab
* Drug: fluorouracil
* Drug: irinotecan hydrochloride
* Drug: leucovorin calcium
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed colorectal cancer Advanced or metastatic disease Scheduled to receive first- or second-line therapy for metastatic disease No cerebral metastases or symptomatic or uncontrolled meningeal disease PATIENT CHARACTERISTICS: WHO performance status 0-2 ANC ≥ 2,000/mm^3 Platelet count ≥ 100,000/mm^3 Total bilirubin ≤ 2 times upper limit of normal (ULN) AST and ALT ≤ 3 times ULN Alkaline phosphatase ≤ 5 times ULN Not pregnant or nursing Fertile patients must use effective contraception No intestinal blockage No complete dihydropyrimidine dehydrogenase deficiency No chronic inflammatory disease of the colon No other cancer except for nonmelanoma skin cancer or curatively treated carcinoma of the cervix or breast No other severe condition, or condition that is likely to worsen, including any of the following: Unstable heart disease Myocardial infarction within the past 6 months Active uncontrolled infection No contraindication to atropine PRIOR CONCURRENT THERAPY: See Disease Characteristics Recovered from prior anticancer therapy More than 4 weeks since prior and no other concurrent investigational therapy Prior adjuvant chemotherapy allowed No prior fluorouracil or irinotecan hydrochloride No other concurrent anticancer therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: cetuximab|nan|
|Drug: fluorouracil|nan|
|Drug: irinotecan hydrochloride|nan|
|Drug: leucovorin calcium|nan|
|Other: pharmacological study|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of hematologic and gastrointestinal tolerance to therapy |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy |  |  | 
| Genetic and genomic tumor parameters that could interfere with and predict the toxicity and/or antitumor efficacy of therapy |  |  | 
| Time to progression |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV colon cancer, recurrent colon cancer, stage IV rectal cancer, recurrent rectal cancer