Ncctg N0872 (alliance): A Randomized Placebo- Controlled Phase Ii Trial of Bevacizumab Plus Dasatinib in Patients with Recurrent Glioblastoma (Gbm)

2004 Background: Preclinical data indicate that Src kinase signaling is markedly upregulated at the invasive GBM front following administration of the anti-VEGF antibody bevacizumab (Bev). The broad spectrum Src kinase inhibitor dasatinib can effectively block Bev-induced glioma invasion (Huveldt et al, 2013). We therefore hypothesized that combining dasatinib with Bev could increase Bev efficacy in the recurrent GBM setting. Methods: Eligible patients (pts) had progressive GBM; up to 1 chemotherapy regimen was allowed for recurrent disease. Following a 16 pt phase I dose escalation trial that established Bev 10 mg/kg every 2 weeks in combination with dasatinib 100 mg PO bid as the phase II dose of the combination, the randomized placebo-controlled phase II portion of the trial was initiated. The study followed a 2:1 randomization procedure with 85% power to detect a 20% difference in progression-free survival at 6 months (mo) (primary endpoint) between the two arms, and a type I error rate of 0.15 Result...