
Dose escalation:
toxicity
The dose escalation cohort was formulated based on a traditional 3 + 3 design in which patients in sequential dose-level cohorts received increasing doses of FTD/TPI (25, 30, or 35 m/m2/dose, twice per day for days 1-5) and IRI (150 or 180 mg/mAt least 3 evaluable patients were treated with each dose; 6 patients were treated at the RP2D. An increase in subsequent doses was allowed only after the previous dose was determined to be safe as per protocol. Intra-patient dose escalation was not permitted. The RP2D was defined as the highest dose at which 1/3 or 2/6 of the treated evaluable patients experienced dose-limiting toxicity (DLT) during cycles 1 or 2. The expansion cohort was initiated as soon as the RP2D had been established; up to 15 patients were enrolled in parallel and administered FTD/TPI and IRI with BEV at the RP2D.