MOMENTUM: A phase I trial investigating two schedules of capecitabine with aflibercept in gastrointestinal and breast cancer patients

Abstract Background While data from preclinical and clinical studies provide a strong rationale for combining capecitabine with anti-angiogenic agents, clinical development of this fluoropyrimidine in combination with aflibercept has lagged behind other treatments. We conducted a non-randomised, non-comparative, two-arm, phase I trial to address this unmet need. Patients and Methods Chemorefractory gastrointestinal and breast cancer patients were sequentially recruited into a continuous (Arm A, starting dose 1100 mg/m2/day) or intermittent (Arm B, 2 weeks on/1 week off, starting dose 1700 mg/m2/day) capecitabine dosing arm. Aflibercept was administered at a flat dose of 6 mg/kg every 3 weeks in both arms. A classical 3+3, dose-escalation design was used. The primary objective was to establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs) and recommended dose for phase II trials (RPD2). Results Thirty-eight eligible patients were recruited of whom 33 were assessable for DLTs (15 in arm A and 18 in arm B). Fourteen had colorectal cancer, 8 gastric cancer and 11 breast cancer. DLTs included grade 2 hand-foot syndrome, grade 2 anorexia considered unacceptable by the patient and grade 3 hypertension. The RP2D for capecitabine was established at 1300 mg/m2/day in Arm A and 2500 mg/m2/day in Arm B with treatment-related grade ≥3 adverse events occurring in 47% and 50% of patients, respectively. Among 26 assessable patients, the objective response rate was 15.4% in Arm A and 7.7% in Arm B. Conclusion Combining capecitabine with aflibercept is feasible, and associated with a manageable safety profile and some anti-tumour activity chemorefractory gastrointestinal and breast cancer patients.