Phase II-III Study of an Optimized LV-5FU-Oxaliplatin Strategy in Metastatic Colorectal Cancer. Optimox2 Study. C02-2

Brief Summary

Detailed Description

OBJECTIVES: Primary * Compare progression-free survival of patients with inoperable metastatic colorectal cancer treated with oxaliplatin, leucovorin calcium, and fluorouracil with vs without maintenance leucovorin calcium and fluorouracil. * Demonstrate that time of disease control (TDC) can be increased by 15% at 9 months and that maintenance therapy can be avoided. Secondary * Compare the overall survival and response rate in patients treated with these regimens. * Compare the salvage surgery rate in patients treated with these regimens. * Compare the tolerability of these regimens in these patients. * Compare the quality of life in patients treated with these regimens. * Compare the duration of chemotherapy-free intervals in patients treated with these regimens. * Compare the pharmacoeconomy and pharmacogenetics of these regimens in these patients. OUTLINE: This is a randomized, controlled, open-label, multicenter study. Patients are stratified according to participating center, performance status (0-1 vs 2), number of metastatic sites (1 vs \> 1), age (18-50 years vs 51-75 years vs 76-80 years), adjuvant chemotherapy, and baseline alkaline phosphatase (≤ 3 times upper limit of normal \[ULN\] vs \> 3 times ULN). Patients are randomized to 1 of 2 treatment arms. Arm I * FOLFOX chemotherapy: Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance chemotherapy. * Maintenance chemotherapy: Patients receive leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression on maintenance chemotherapy receive 6 additional courses of FOLFOX as above. Patients with continued disease progression while receiving the additional courses of FOLFOX proceed to irinotecan-based chemotherapy off study. Arm II * FOLFOX chemotherapy: Patients receive 6 courses of FOLFOX as in arm I. Patients with disease progression on FOLFOX receive 6 additional courses of FOLFOX. Patients with continued disease progression while receiving the additional courses of FOLFOX proceed to irinotecan-based chemotherapy off study. In both arms, patients with stable or responding disease may undergo surgical resection after completion of the initial 6 courses of FOLFOX. Quality of life is assessed at baseline, after courses 4 and 6, and then every 2-3 months thereafter. After completion of study treatment, patients are followed at 1 month and then every 3 months thereafter. PROJECTED ACCRUAL: A total of 600 patients will be accrued for this study.

Primary Outcomes