Background: 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 was defined as ≥70% of pts on the experimental arm completing ≥70% of the planned treatment with ≤30% of pts having any ≥ Grade (G) 3 Adverse Events (AEs). (ANZCTR #ACTRN12615000407594) Results: 60 pts have been randomized in Stage 1 (Arm A = 39, Arm B = 21). Patient characteristics (age, gender, performance status, and extent of resection) were well matched. All 39 pts in the experimental arm completed at least 80% of the planned V treatment, receiving at least 70% of the full V dose and 80% of the planned RT dose. Eleven pts (28%) in the experimental arm experienced ≥ G3 AEs during concurrent treatment. The commonest severe AEs were seizures observed in 3pt in each arm, 7% in the experimental arm and 15% in the standard treatment arm followed by thrombocytopenia seen in 2 pts in each arm, 5% in the experimental arm and 10% in the standard arm. Conclusions: Stage 1 of VERTU satisfied the predefined feasibility and safety criteria and the study will continue until the accrual target (120pts) is reached (anticipated mid-2018). Efficacy endpoints will be analyzed and reported after completion of accrual. Clinical trial information: 12615000407594.