ACTR-14. PHASE I STUDY OF AZD1775 WITH RADIATION THERAPY (RT) AND TEMOZOLOMIDE (TMZ) IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA (GBM) AND EVALUATION OF INTRATUMORAL DRUG DISTRIBUTION (IDD) IN PATIENTS WITH RECURRENT GBM

ABSTRACT: Abstract AZD1775 is an oral small molecular inhibitor of the G2/M checkpoint regulator Wee1. The Adult Brain Tumor Consortium 1202 trial (NCT01849146) is a phase I, open label, multicenter dose-finding study of AZD1775 in combination with standard RT and TMZ followed by an IDD study for patients undergoing surgery for recurrent GBM. Dose of AZD1775 was increased in a 3 + 3 design M-F during concurrent RT/TMZ and x 5d/28d cycle with adjuvant TMZ in separate cohorts. A combination cohort with both concurrent and adjuvant AZD1775 at MTD and analysis of PK/PD and IDD at MTD in patients undergoing surgery for recurrent GBM followed. MTD was 200 mg for concurrent with 2/6 patients experiencing DLTs (grade 4 neutropenia, grade 3 ALT elevation). MTD for the adjuvant cohort was 425 mg with 1/6 pati

SUBMITTER: Alexander B 

PROVIDER: S-EPMC6216169 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature