RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, irinotecan, and capecitabine, 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) may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of capecitabine when given together with oxaliplatin and irinotecan and to see how well they work in treating patients with advanced or metastatic colorectal cancer that cannot be removed by surgery.
OBJECTIVES: Primary * Determine the maximum tolerated dose and recommended phase II dose of capecitabine administered in combination with oxaliplatin and irinotecan in patients with unresectable advanced or metastatic colorectal cancer. (Phase I) * Determine the efficacy of this regimen in these patients. (Phase II) Secondary * Determine the tolerability of this regimen in these patients. (Phase II) OUTLINE: This is a multicenter, phase I dose-escalation study of capecitabine followed by a phase II study. * Phase I: Patients receive oxaliplatin IV over 2 hours on days 1 and 15, irinotecan IV over 1 hour on days 8 and 22, and oral capecitabine twice daily on days 1-29. Treatment repeats every 5 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. * Phase II: Patients receive capecitabine at the MTD and irinotecan and oxaliplatin as in phase I. After completion of study treatment, patients are followed every 2 months for 1 year and then every 4 months thereafter. PROJECTED ACCRUAL: A total of 23-32 patients (3-12 for the phase I portion and 20 for the phase II portion) will be accrued for this study within 2.75 years
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
23
Kantonsspital Graubuenden
Chur, Switzerland
Hopital Cantonal Universitaire de Geneve
Geneva, Switzerland
Hirslanden Klinik Aarau
Lausanne, Switzerland
City Hospital Triemli
Zurich, Switzerland
capecitabine + oxaliplatin + irinotecan dose finding
Determine the maximum tolerated dose and recommended phase II dose of capecitabine administered in combination with oxaliplatin and irinotecan in patients with unresectable advanced or metastatic colorectal cancer. (Phase I)
Time frame: 30 days
Efficacy of Oxaliplatin, Irinotecan, and Capecitabine
Determine the efficacy of this regimen in these patients (Phase II)
Time frame: 2 months
Objective response (CR or PR) as measured after completion of study treatment
Time frame: 2 months
Adverse events as measured after completion of study treatment
Time frame: 2 months
Time to progression
Time frame: life-long
Time to treatment failure as measured after completion of study treatment
Time frame: life-long
Overall survival
Time frame: life-long
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