Comparing Two Combination Chemotherapy Regimens in Treating Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which regimen of combination chemotherapy is more effective for metastatic colorectal cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of two combination chemotherapy regimens in treating patients who have metastatic colorectal cancer.

Detailed Description
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OBJECTIVES: Compare the efficacy of intermittent high-dose oxaliplatin in combination with a simplified bimonthly regimen of leucovorin calcium (LV) and fluorouracil (5-FU) vs standard dose oxaliplatin in combination with the standard bimonthly regimen of LV and 5-FU in patients with metastatic colorectal cancer. Determine the time to treatment failure, tolerance, response rate, and overall survival in patients treated with these 2 regimens. Compare quality of life of these patients treated with these regimens. OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to treatment center, performance status (0-1 vs 2), and number of metastatic sites (1 vs more than 1). Patients are randomized to one of two treatment arms. Arm I: Patients receive oxaliplatin IV over 2 hours on day 1, and leucovorin calcium IV over 2 hours followed by fluorouracil (5-FU) IV over 22 hours on days 1 and 2. Arm II: Patients receive oxaliplatin IV and leucovorin calcium IV over 2 hours followed by 5-FU IV over 46 hours beginning on day 1 for courses 1-6 and 19-24. For courses 7-18, patients receive leucovorin calcium IV followed by 5-FU IV as above beginning on day 1. Courses repeat every 14 days in both arms in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, after courses 4 and 6, and every 6 courses thereafter. Patients are followed monthly for 3 months and then every 3 months thereafter. PROJECTED ACCRUAL: A total of 460 patients (230 per treatment arm) will be accrued for this study within 18 months.

Official Title
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Phase III Study of An Optimized LV-5FU-Oxaliplatin Regimen in Metastatic Colorectal Cancer. C99-1.

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: FOLFOX regimen
* Drug: fluorouracil
* Drug: leucovorin calcium
* Drug: oxaliplatin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed unresectable metastatic adenocarcinoma of the colon or rectum Bidimensionally measurable or evaluable disease outside previously irradiated area No bone metastasis as target lesion At least 1 cm if spiral CT scan OR At least 2 cm if conventional CT scan No CNS metastasis No symptomatic ascites or pleural effusion that is not evacuated No total or partial bowel obstruction PATIENT CHARACTERISTICS: Age: 18 to 80 Performance status: ECOG 0-2 WHO 0-2 Life expectancy: Not specified Hematopoietic: Neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Alkaline phosphatase less than 5 times upper limit of normal (ULN) Renal: Creatinine less than 3 times ULN No uncontrolled hypercalcemia Cardiovascular: No uncontrolled congestive heart failure, angina pectoris, hypertension, or arrhythmias Other: No peripheral sensory neuropathy No prior significant neurologic or psychiatric disorders No other malignancy within past 5 years except adequately treated carcinoma in situ of the cervix or basal or squamous cell skin carcinoma No active infection No other concurrent serious disease Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: No prior immunotherapy for metastatic disease Chemotherapy: Prior adjuvant chemotherapy allowed, provided progression-free interval of more than 6 months since end of last course No prior oxaliplatin or irinotecan No prior chemotherapy for metastatic disease No other concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics No concurrent radiotherapy Surgery: Concurrent surgery allowed Other: At least 30 days since other prior investigational drugs No other concurrent investigational treatment No other concurrent antitumoral treatment

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: Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: FOLFOX regimen|nan|
|Drug: fluorouracil|nan|
|Drug: leucovorin calcium|nan|
|Drug: oxaliplatin|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 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, recurrent colon cancer, recurrent rectal cancer, adenocarcinoma of the colon, adenocarcinoma of the rectum