Geino 1402: A Phase Ib Dose-Escalation Study Followed By An Extension Phase To Evaluate Safety And Efficacy Of Crizotonib In Combination With Temozolomide (Tmz) And Radiotherapy (Rt) In Patients With Newly Diagnosed Glioblastoma (Gb): Results Of The Dose-Escalation Phase.

2054Background: Crizotinib is an ALK, ROS-1 and c-MET inhibitor with an interesting rationale to be tested in NDGB due to the role of MET signaling in gliomagenesis and stem cell maintenance and capability of midkine, a recently discovered ALK ligand, to promote resistance of glioma cells to anticancer therapies such as RT and TMZ. Primary objective of this trial was to determine maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of crizotinib in combination with RT and TMZ. Methods: Eligible patients received crizotinib with standard RT and TMZ and afterwards continued crizotinib daily with sequential adjuvant TMZ. Additional treatment with crizotinib beyond 6 TMZ cycles was allowed at the discretion of physician. Crizotinib MTD was determined using a standard “3+3” dose escalation design. Dose-limiting toxicities were observed during the first 12 weeks of therapy. Results: 12 patients (median age: 53,5 (33-60 y)) were enrolled in 3 crizotinib cohorts (200 mg/QD, 250 mg/QD and 200 mg/BID). ...