DD-02PHARMACODYNAMIC BIOMARKER ASSESSMENTS IN A PHASE I/II TRIAL OF THE HYPOXIA-ACTIVATED PRODRUG TH-302 AND BEVACIZUMAB IN BEVACIZUMAB-REFRACTORY RECURRENT GLIOBLASTOMA

ABSTRACT: BACKGROUND: Glioblastoma (GBM) remains an incurable malignancy with rapid progression and poor survival. GBM exhibits a hypoxic nature, and treatment with bevacizumab (BEV) may increase intratumoral hypoxia. TH-302 is an investigational prodrug that selectively releases the DNA cross-linker (Br-IPM) under hypoxic conditions. A phase I/II trial (NCT01403610) is evaluating the safety and efficacy of combined TH-302 and BEV treatment in patients with BEV-refractory GBM and investigating pharmacodynamics biomarkers. METHODS: Patients were randomized to TH-302 single dose (575 mg/m2) or placebo, administered one day before surgery, followed by TH-302 (240-670 mg/m2) + BEV treatment until disease progression. Before surgery, pimonidazole (Pimo) was administered to label hypoxia and the excised t

SUBMITTER: Cavazos D 

PROVIDER: S-EPMC4218032 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature