The effect of motesanib treatment on the gallbladder: A randomized phase Ib study in patients (pts) with advanced solid tumors.

e13555 Background: Gallbladder toxicity, including cholecystitis, has been seen in studies of motesanib, an orally administered small-molecule antagonist of VEGFRs 1, 2 and 3; PDGFR; and Kit. We assessed effects of motesanib on gallbladder size and function in pts with advanced solid tumors. Methods: Pts (≥18 y) with advanced metastatic solid tumors ineligible for or having progressed on standard-of-care therapies, with ECOG ≤2, and with no history of cholecystitis or biliary disease were randomized 2:1:1 to receive 3-wk cycles of motesanib 125 mg once daily (Arm A); 75 mg twice daily (BID), 14 d on/7 d off (Arm B); or motesanib 75 mg BID, 5 d on/2 d off (Arm C). The primary endpoints were mean change from baseline in gallbladder size (volume by ultrasound per independent review) and function (ejection fraction [EF] by CCK-HIDA per investigator assessment). Ultrasound and CCK-HIDA were performed at screening, regular intervals during the study, and the safety follow-up. A linear regression model assessed ...