Combination Chemotherapy as First-Line Therapy in Treating Older Patients With Metastatic Colorectal Cancer That Cannot Be Removed By Surgery

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin, and irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) in different doses or combinations may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective in treating colorectal cancer. PURPOSE: This randomized clinical trial is studying how well fluorouracil works together with leucovorin with or without irinotecan in treating older patients with metastatic colorectal cancer .

Detailed Description
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OBJECTIVES: Primary Compare the progression-free survival of elderly patients with unresectable metastatic colorectal cancer treated with 1 of 2 different chemotherapy regimens comprising fluorouracil and leucovorin calcium with vs without irinotecan hydrochloride. Secondary Compare the tumor response rate and overall survival of patients treated with these regimens. Compare the tolerability of these regimens in these patients. Compare the quality of life of patients treated with these regimens. OUTLINE: This is a randomized, multicenter, prospective study. Patients are stratified according to participating center, gender, Karnofsky score (60-70% vs 80-90% vs 100%), associated comorbidities (Charlson Index 0 vs 1-2 vs 3+), age (75 to 79 years vs ≥ 80 years), alkaline phosphatase level (≤ 2 times normal vs > 2 times normal), and prior adjuvant chemotherapy (yes vs no). Patients are randomized to 1 of 4 treatment arms. Arm I: Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 22 hours on days 1 and 2. Arm II: Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 46 hours on days 1 and 2. Arm III: Patients receive leucovorin calcium and fluorouracil as in arm I and irinotecan hydrochloride IV over 90 minutes on day 1. Arm IV: Patients receive leucovorin calcium and fluorouracil as in arm II and irinotecan hydrochloride as in arm III. In all arms, treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity. Patients undergo surgery within 3-10 weeks after completing chemotherapy. Quality of life is assessed at baseline and then every 2 months thereafter. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 282 patients will be accrued for this study.

Official Title
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Randomized Study of Classic vs Simplified Leucovorin Calcium and Fluorouracil With or Without Irinotecan in Patients Aged At Least 75 Years With Advanced Colorectal Cancer

Conditions
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Colorectal Cancer

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


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the colon or rectum Metastatic disease Unresectable disease Measurable disease that is outside the field of prior irradiation No brain metastases PATIENT CHARACTERISTICS: Karnofsky performance status 60-100% Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Transaminases ≤ 5 times normal Bilirubin ≤ 1.5 times normal Alkaline phosphatase < 3 times normal (5 times normal if due to hepatic involvement) Creatinine clearance > 45 mL/min Life expectancy > 3 months No psychological, social, or geographical situation that would preclude study treatment No chronic diarrhea or enteropathy No coronary insufficiency or symptomatic cardiac disease No other malignancy unless curatively treated No contraindication to chemotherapy PRIOR CONCURRENT THERAPY: At least 6 months since prior adjuvant chemotherapy for the primary tumor No prior extensive resection No other concurrent anticancer therapy

Ages Eligible for Study
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Minimum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: LV5FU2 classique<br>LV5FU2 classique | Drug: fluorouracil<br> <br> Drug: leucovorin calcium<br> <br> |
| Experimental: LV5FU2 classique + irinotécan<br>LV5FU2 classique + irinotécan | Drug: fluorouracil<br> <br> Drug: irinotecan hydrochloride<br> <br> Drug: leucovorin calcium<br> <br> |
| Active Comparator: LV5FU2 simplifié<br>LV5FU2 simplifié | Drug: fluorouracil<br> <br> Drug: leucovorin calcium<br> <br> |
| Experimental: LV5FU2 simplifié+ irinotécan<br>LV5FU2 simplifié + irinotécan | Drug: fluorouracil<br> <br> Drug: irinotecan hydrochloride<br> <br> Drug: leucovorin calcium<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (survie sans progression) | survie sans progression | 2011 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (survie globale) | survie globale | 2011 | 

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