Adaptive, Individualized Dose Escalation of Fluorouracil-Based Chemotherapy for Gastrointestinal Cancer: Pilot Study of the FOX Regimen

What this Trial Is About

Researchers are evaluating an adaptive, individualized dose escalation approach of 5-fluorouracil (5-FU) chemotherapy combined with oxaliplatin for patients with metastatic or locally advanced gastrointestinal cancers, including colorectal, stomach, esophagus, appendix, small bowel, and ampullary cancers. This single-arm trial aims to determine the feasibility and effectiveness of increasing the 5-FU dose in patients who tolerate the initial dose well, using a clinical algorithm to guide dosing. The study is sponsored by Dartmouth-Hitchcock Medical Center and does not specify a phase. Participants will receive the FOX chemotherapy regimen, which includes oxaliplatin 85 mg/m2 and leucovorin calcium 350 mg intravenously on Day 1, with a continuous 46-hour infusion of 5-FU starting at 2,400 mg/m2. Over Cycles 2 to 4, the 5-FU dose will be adjusted toward a maximum of 3,200 mg/m2 based on tolerance, using a dose-escalation algorithm. Each treatment cycle lasts 14 days, and the dose intensity of both drugs will be monitored through Cycle 6. During the study, participants will undergo clinical evaluations including imaging of the chest, abdomen, and pelvis for staging, laboratory tests to monitor blood counts and organ function, and measurement of drug exposure and plasma uracil concentration. The main outcome is the proportion of patients who receive a dose-intensified 5-FU by Cycle 6. Secondary outcomes include response rate, progression-free survival, and chemotherapy dose intensity. The study also tracks safety through lab monitoring and excludes patients with specific health conditions or prior treatments. Total participation time includes treatment cycles and follow-up assessments up to 12 months.

Individualized Dose Escalation of 5-FU for Gastrointestinal Cancer