LAUSR

G (1000 mg) intravenously on Day (D) 1, D8, and D15 of cycle (C) 1, and on D1 of subsequent cycles (Figure). The standard infusion rate will be administered in C1, starting on D1 at 50 mg/hour, then increase by 50 mg/hour every 30 minutes to a maximum of 400 mg/hour. If no IRR or a Gr 1 IRR occurs, C1D8 (and subsequently C1D15) will start at 100 mg/hour, then increase by 100 mg/hour every 30 minutes to a maximum of 400 mg/hour. If a Gr 2–3 IRR occurs during C1D1 or C1D8, the next infusion (C1D8 or C1D15, respectively) will be administered at the same rate as C1D1. If no Gr ≥3 IRR occurs in C1, all subsequent infusions will be administered via a faster 90-minute SDi; 100 mg/hour for 30 minutes, then 900 mg/hour for 60 minutes. If a Gr 3 IRR occurs during any SDi administration, the next dose of G will be administered at the standard infusion rate. The investigator will decide if the pt can restart with the SDi. The primary endpoint is incidence of Gr ≥3 IRRs during C2 in pts who had previously received G at the standard infusion rate during C1 without experiencing a Gr ≥3 IRR. Secondary safety endpoints include adverse events, time to IRRs, type and duration of Gr ≥3 IRRs and duration of G administration by cycle. Secondary efficacy endpoints include overall response rate, PFS, overall survival and complete response at 30 months. It is estimated that 112 pts will be enrolled. Acknowledgment: Third-party medical writing assistance, under the direction of Miguel Canales, was provided by Russell Craddock and Louise Profit of Gardiner-Caldwell Communications, and was funded by F. Hoffmann-La Roche Ltd.