Final Report on NCCTG N0877 (Alliance): A Phase II Randomized, Placebo-Controlled Trial of Chemoradiotherapy with or without Dasatinib for Glioblastoma.

Background: Dasatinib is an oral inhibitor of the Src kinase family, with preclinical data indicating impact on gliomagenesis, tumor invasion, and radiosensitivity.

Methods: NCCTG N0877 is a phase 1 dose escalation and phase II randomized study evaluating the maximum tolerated dose (MTD), safety, and efficacy of dasatinib with radiation and temozolomide (TMZ) for glioblastoma. Following identification of the MTD, adult patients with a histologic diagnosis of glioblastoma were randomized 2:1 between dasatinib given with standard concurrent and adjuvant TMZ, versus placebo with standard concurrent and adjuvant TMZ. Radiation dose was 60 Gy in 30 fractions. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), toxicity, and quality of life.

Results: Thirteen patients were enrolled on the phase I component and established the MTD and phase II dose of 150 mg given daily. A total of 204 patients were enrolled on the phase II component. OS was not different between arms (median OS 15.6 months for dasatinib compared to 19.3 months for placebo, hazard ratio:1.21 favoring placebo, 95% CI: 0.88-1.65, logrank p-value: 0.238). Similarly, PFS was not significantly different between dasatinib and placebo arms. There was significantly increased anemia, nausea, and creatinine elevation with dasatinib, but significantly more grade 3 lymphopenia with placebo.

Conclusions: The addition of dasatinib to standard chemoradiation did not improve outcomes for patients with glioblastoma.