Combination Chemotherapy in Treating Patients With Advanced or 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. PURPOSE: Randomized phase II trial to study the effectiveness of combination chemotherapy in treating patients who have advanced or metastatic colorectal cancer.

Detailed Description
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OBJECTIVES: Compare the efficacy of different schedules of irinotecan in combination with capecitabine as first-line therapy, in terms of objective response rate, in patients with advanced or metastatic colorectal cancer. Compare the time to treatment failure, time to progression, and overall survival of patients treated with these regimens. Compare the safety profile, in terms of toxicity, of these regimens in these patients. Determine the quality of life in patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to performance status (0 vs 1); disease symptoms, including pain, weight loss, loss of appetite, malaise, and fever of unknown origin (yes vs no); weight loss during the past 6 months (more than 5% vs 5% or less); and disease-free interval (more than 6 months vs 6 months or less). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive irinotecan IV over 1 hour on days 1, 8, 15, 22, and 29 and oral capecitabine twice daily on days 1-14 and 22-35. Arm II: Patients receive irinotecan IV over 1 hour on days 1 and 22 and oral capecitabine as in arm I. Treatment in both arms repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, on day 1 of each course, and at the first visit after treatment failure. Patients are followed every 12 weeks for 1 year and then every 6 months thereafter. PROJECTED ACCRUAL: A total of 28-74 patients (14-37 per treatment arm) will be accrued for this study.

Official Title
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A Randomized Phase II Trial Of Capecitabine And Different Schedules Of Irinotecan As First Line Treatment For Advanced Or Metastatic Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Irinotecan 70 mg/m2
* Drug: Irinotecan 240 mg/m2


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed advanced or metastatic colorectal cancer Unresectable disease At least 1 bidimensionally measurable lesion At least 2 cm in perpendicular diameters No evidence of CNS metastases PATIENT CHARACTERISTICS: Age: 18 to 75 Performance status: 0-1 Life expectancy: At least 3 months Hematopoietic: WBC at least 3,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin normal SGOT/SGPT no greater than 2.5 times upper limit of normal (ULN) Alkaline phosphatase no greater than 2.5 times ULN Renal: Creatinine no greater than 1.25 times ULN Cardiovascular: No clinically significant cardiac disease No congestive heart failure No New York Heart Association class III or IV heart disease No symptomatic coronary artery disease No uncontrolled cardiac arrhythmia No myocardial infarction within the past year Gastrointestinal: No evidence of dysphagia No malabsorption or intestinal obstruction that would affect absorption or excretion of study drugs No chronic diarrhea Other: No other malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix or localized nonmelanoma skin cancer No psychiatric disability that would preclude study compliance No other significant medical condition Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy for advanced or metastatic disease Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: At least 4 weeks since prior major surgery to the gastrointestinal tract Other: No concurrent therapy for history of seizures or CNS disorder

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
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A<br>Irinotecan i.v. 70 mg/m2, day 1, 8, 15, 22, 29; Capecitabine p.o. 2 x 1000 mg/m2, d1-14, d22-35; | Drug: Irinotecan 70 mg/m2<br>* Irinotecan i.v. 70 mg/m2, day 1, 8, 15, 22, 29<br>|
| Active Comparator: Arm B<br>Irinotecan i.v. 240 mg/m2 day 1 and day 22; Capecitabine p.o. 2 x 1000 mg/m2, d1-14, d22-35; | Drug: Irinotecan 240 mg/m2<br>* Irinotecan i.v. 240 mg/m2 day 1 and day 22<br>|

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 III colon cancer, stage IV colon cancer, stage III rectal cancer, stage IV rectal cancer