Background: Dasatinib is a potent oral ATP competitive multi-targeted kinase inhibitor of multiple members of the Src kinase family known to be involved in gliomagenesis, tumor invasion, and radiosensitivity. N0877 is a phase I/randomized phase II trial evaluating the combination of dasatinib, radiation (RT) and temozolomide (TMZ) in newly diagnosed GBM. Methods: Following a 13 patient phase I dose escalation trial which established the MTD and phase II dose of dasatinib to be 150 mg PO daily when given with RT and TMZ, 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 hazard ratio of 1.6 or higher in overall survival (OS) between the two arms and a type I error rate of 0.10. Dasatinib or placebo was given orally for 42 days, beginning with the first day of RT (total dose 60 Gy) and first dose of TMZ (75 mg/m2/d). Following a 24 - 42 day rest, patients then received 6 cycles (28 day cycles) of dasatinib or placebo (days 1-28) and TMZ (days 1-5). At the completion of 6 cycles of TMZ + dasatinib/placebo, patients continued on dasatinib/placebo only (28 day cycles) until progressive disease. Results: Data from 187 of 196 patients enrolled were available for analysis. Median follow-up was 12.6m for dasatinib (N = 133 pts), and 14m for placebo (N = 63 pts). There was no significant difference in PFS between dasatinib and placebo (6.7m vs 7.8m, respectively; HR 0.80 favoring placebo, 95% CI 0.57-1.1, p = 0.18) or OS (15.5m vs 20.6m; HR 0.71 favoring placebo, 95% CI 0.46-1.1, p = 0.12). Response rate (CR+PR) was 10.5% for dasatinib and 8.3% in placebo arm (p = 0.77). The overall incidence of grade 3 or higher hematologic toxicity was lower in the dasatinib arm (43.9% vs 68.8%, p = 0.0012) primarily due to lower rates of lymphopenia. Grade 3 or higher non-hematologic toxicities were similar between arms (53.8% vs 41.3%, p = 0.1384). Analysis by MGMT status will be forthcoming. Conclusions: The combination of the Src kinase inhibitor dasatinib with standard RT/TMZ did not improve the outcome of newly diagnosed GBM patients as compared to standard therapy alone. Clinical trial information: NCT00869401