Irinotecan, Fluorouracil, Leucovorin, and Oxaliplatin as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as irinotecan, fluorouracil, leucovorin, and oxaliplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy as first-line therapy in treating patients who have metastatic colorectal cancer.

Detailed Description
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OBJECTIVES: Primary Determine the tumor response rate in patients with metastatic colorectal cancer treated with irinotecan, fluorouracil, leucovorin calcium, and oxaliplatin as first-line treatment. Secondary Determine the time to tumor progression, time to treatment failure, and overall survival of patients treated with this regimen. Determine the toxicity of this regimen in these patients. Determine the quality of life of patients treated with this regimen. Determine whether UGT1A1 polymorphism is related to toxicity (especially leukopenia, diarrhea, or neutropenia) or response in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive irinotecan IV over 90 minutes and oxaliplatin IV over 2 hours on day 1 and leucovorin calcium IV and fluorouracil IV over 90 minutes on days 2-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, before each chemotherapy course, and at the end of treatment. Patients are followed every 3 months until 5 years after registration.

Official Title
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Phase II Trial Of Irinotecan + 5-Fluorouracil + Leucovorin + Oxaliplatin As First-Line Treatment For Metastatic Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: fluorouracil
* Drug: irinotecan hydrochloride
* Drug: leucovorin calcium
* Drug: oxaliplatin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of colorectal adenocarcinoma Metastatic disease Not curable by surgery or amenable to radiotherapy with curative intent Measurable disease Patients with only lesions measuring ≥ 1 cm but < 2 cm must use spiral CT scan for pre- and post-treatment tumor assessments No known CNS metastases or carcinomatous meningitis PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy At least 12 weeks Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic AST ≤ 5 times upper limit of normal (ULN) Bilirubin ≤ 0.5 mg/dL above ULN Renal Creatinine ≤ 1.5 times ULN OR Creatinine clearance ≥ 60 mL/min Cardiovascular No unstable angina No symptomatic congestive heart failure No serious uncontrolled cardiac arrhythmia Pulmonary No prior clinical diagnosis of interstitial lung disease Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active or uncontrolled infection No other concurrent serious illness No pre-existing paraesthesias/dysesthesias of ≥ grade 2 that would interfere with function No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or adequately treated noninvasive carcinomas PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent sargramostim (GM-CSF) Chemotherapy At least 6 months since prior adjuvant chemotherapy No prior fluorouracil for advanced colorectal cancer No prior adjuvant oxaliplatin No prior adjuvant irinotecan Endocrine therapy Not specified Radiotherapy No prior radiotherapy to > 25% of bone marrow Surgery At least 4 weeks since prior major surgery

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: irinotecan + oxaliplatin + leucovorin + fluorouracil<br>Patients receive irinotecan IV over 90 minutes and oxaliplatin IV over 2 hours on day 1 and leucovorin calcium IV and fluorouracil IV over 90 minutes on days 2-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, before each chemotherapy course, and at the end of treatment. Patients are followed every 3 months until 5 years after registration. | Drug: fluorouracil<br> <br> Drug: irinotecan hydrochloride<br> <br> Drug: leucovorin calcium<br> <br> Drug: oxaliplatin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| tumor response rate |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to progression |  | Up to 5 years | 
| overall survival |  | Up to 5 years | 
| time to treatment failure |  | Up to 5 years | 
| quality of life |  | Up to 5 years | 

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