A randomized phase 2 trial of veliparib (V), radiotherapy (RT) and temozolomide (TMZ) in patients (pts) with unmethylated MGMT (uMGMT) glioblastoma (GBM): Feasibility and safety outcomes (the VERTU study).

2045Background: TMZ offers minimal benefit in uMGMT GBM pts. V is synergistic with both RT and TMZ in preclinical models, safe when combined with either RT or TMZ clinically but the triplet (V+RT+TMZ) is poorly tolerated. This study examines a novel approach to patients with uMGMT GBM. Methods: VERTU is a randomized Phase 2 trial comparing Arm A (experimental arm) = RT (60gy/30 fractions) + V (200mg BID) followed by TMZ (150-200mg/m2D 1-5) + V (40mg bid, D 1-7) every 28 days for 6 cycles vs Arm B (Standard of care) = RT (60gy/30 fractions) + TMZ (75mg/m2 daily) followed by TMZ (150-200mg/m2D 1-5) every 28 days for 6 cycles in pts with newly diagnosed uMGMT GBM. The study aims to randomize 120 pts (2:1 to the experimental arm). The primary endpoint is 6 months Progression Free Survival (6PFS) with multiple secondary and tertiary endpoints. Evaluation of feasibility and safety was planned after completion of RT in the first 60 pts (Stage 1). Acceptable feasibility and safety criteria for study continuation ...