Fluorouracil and Irinotecan With or Without Leucovorin Compared With Observation in Treating Patients Who Have Undergone Surgery for Stage II Colon Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as irinotecan, leucovorin, and fluorouracil, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them after surgery may kill any remaining tumor cells. It is not yet known whether combination chemotherapy is more effective than observation alone in treating patients who have undergone surgery for colon cancer. PURPOSE: This randomized phase III trial is studying irinotecan and fluorouracil with or without leucovorin to see how well they work compared to observation alone in treating patients who have undergone surgery for stage II colon cancer.

Detailed Description
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OBJECTIVES: Primary Compare 5-year disease-free survival in patients with resected stage II adenocarcinoma of the colon treated with adjuvant chemotherapy comprising fluorouracil and irinotecan with or without leucovorin calcium vs no adjuvant therapy. Secondary Compare 8-year overall survival in patients treated with these regimens. Compare tolerability of these regimens in these patients. Correlate clinical, histological, and biological prognostic factors with outcome in patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, disease stage (pT3 vs pT4), pathological differentiation (poorly or undifferentiated vs well or moderately differentiated), and microsatellite instability (positive vs negative vs unknown). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients are further randomized to receive 1 of 3 adjuvant chemotherapy regimens. Regimen A: Patients receive irinotecan IV over 90 minutes followed by leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 46 hours on days 1, 15, and 29. Treatment repeats every 42 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Regimen B: Patients receive irinotecan IV over 30-90 minutes followed by leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 24 hours on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 56 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Regimen C: Patients receive irinotecan IV over 60 minutes followed by fluorouracil IV continuously over 48 hours on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 42 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients undergo observation only. Patients are followed every 6 months. PROJECTED ACCRUAL: A total of 1,976 patients (988 per treatment arm [247 each in regimens A and B of arm I and 494 in regimen C of arm I]) will be accrued for this study within 4.5 years.

Official Title
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Randomized Phase III Intergroup Trial in Resected Stage 2 (Dukes B) Colon Cancer: 6-Month Infusional 5FU-CPT11 (+/- Folinic Acid) Versus Observation - Determination of Biologic Predictive and Response Factors

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: FOLFIRI regimen
* Drug: fluorouracil
* Drug: irinotecan hydrochloride
* Drug: leucovorin calcium
* Procedure: adjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the colon Stage II disease (pT3, N0 or pT4, N0) Penetration of the subserosa or serosa No lymph node metastases At least 12 lymph nodes analyzed More than 1 synchronous primary colon tumor allowed Staging determined for the more advanced tumor Curative radical resection within the past 2-8 weeks required Proximal, distal, and radical margins must be free of tumor (R0 resection) No rectal tumors Gross distal margin of the primary tumor must lie above the peritoneal reflection No known familial adenomatous polyposis No hereditary nonpolyposis colorectal cancer No distant metastases PATIENT CHARACTERISTICS: Age 18 to 75 Performance status WHO 0-1 Life expectancy Not specified Hematopoietic Granulocyte count ≥ 2,000/mm^3 Platelet count ≥ 100,000mm^3 Hemoglobin ≥ 10 g/dL Hepatic Bilirubin < 1.25 times upper limit of normal (ULN) No known Gilbert's syndrome Renal Creatinine < 1.25 times ULN Cardiovascular No severe or uncontrolled coronary disease No severe heart failure No uncontrolled arterial hypertension No myocardial infarction within the past year No cerebral vascular accident within the past year Cardiac arrhythmia allowed provided patient is on proper anticoagulation therapy* NOTE: *Aspirin is not considered proper anticoagulation Gastrointestinal No Gardner's syndrome No Turcot's syndrome No Crohn's disease No ulcerative colitis Other No other prior malignancy except adequately treated basal cell skin cancer or carcinoma in situ of the cervix No other serious disease No contraindication to any study drugs No known allergy to leucovorin calcium Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for up to 6 months after study treatment PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior chemotherapy Endocrine therapy Not specified Radiotherapy No prior radiotherapy Surgery See Disease Characteristics Other No other concurrent anticancer therapy No concurrent vitamin supplements containing folic acid

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: FOLFIRI regimen|nan|
|Drug: fluorouracil|nan|
|Drug: irinotecan hydrochloride|nan|
|Drug: leucovorin calcium|nan|
|Procedure: adjuvant therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival at 5 years |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival at 8 years |  |  | 
| Tolerability |  |  | 
| Correlation of clinical, histological, and biological prognostic factors with outcome |  |  | 

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