A Phase I-II Study of Niacin in Patients With Newly Diagnosed Glioblastoma: Safety and Interim Phase II Analysis

PURPOSE Survival of patients with glioblastoma (GB) treated with standard of care (SOC) surgery, radiotherapy, and temozolomide is 15 months with progression free survival at 6 months (PFS-6M) of 53.9%. In vivo studies showed increased survival in mice with GB treated with niacin. This is a first in human Phase I-II study aiming to evaluate safety and efficacy of controlled-release niacin (NiacinCRT ™) added to SOC. METHODS Patients 18–75 years old with newly diagnosed glioblastoma eligible for SOC treatment were included. Phase I evaluated intra-patient dose escalation of niacin (500–3000 mg/d) to determine dose limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Phase II aims to determine if niacin adds ≥ 20% absolute increase in PFS-6M over historical controls. Interim/futility analysis was planned when 24 patients become evaluable for PFS-6M. The study would stop if the conditional power (one-sided Z test) < 20% or futility index > 80%. RESULTS Phase I included 15 patients; median age: 57 years (37–68), 40% women, and 47% with MGMT promoter methylated. The most common side effect was flushing (10/15; 9 grade 1). Two DLTs occurred at 2,500 mg/d niacin (grade 3 thrombocytopenia and hyperbilirubinemia). Niacin dose escalated up to 2000 mg/d is the ongoing RP2D. Interim analysis by central radiology review reported PFS-6M of 82.3% (CI95% 82.14–82.46%). CONCLUSION The MTD dose of niacin added to first line treatment in patients with GB is 2000 mg/d. The interim analysis already showed an absolute increase in PFS-6M of 28%. Trial Registration number: 1. Local ethics board approval - HREBA cc 20-0402 2. Clinicaltrials.gov - NCT04677049. Registered 15 Dec 2020