A phase I-II study of niacin in patients with newly diagnosed glioblastoma: safety and interim phase II analysis.
- 2025-11-28
- Journal of neuro-oncology 176(1)
- Gloria Roldan Urgoiti
- Paula de Robles
- Roger Y Tsang
- Morgan Willson
- Sunita Ghosh
- Muhammad Faruqi
- Gerald Lim
- Shaun Loewen
- Robert Nordal
- Gregory Cairncross
- Catriona Leckie
- Candice C Poon
- V Wee Yong
- PubMed: 41313494
- DOI: 10.1007/s11060-025-05351-z
Study Design
- Type
- Clinical Trial
- Sample size
- n = 24
- Population
- Patients 18–75 years old with newly diagnosed glioblastoma eligible for SOC treatment
- Methods
- Phase I evaluated intra-patient dose escalation of niacin (500–3000 mg/d) to determine DLT, MTD and RP2D. Phase II aims to determine if niacin adds ≥ 20% absolute increase in PFS-6 M over historical controls. Interim/futility analysis planned when 24 patients become evaluable.
- Funding
- Unclear
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-6 M) 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-6 M over historical controls. Interim/futility analysis was planned when 24 patients become evaluable for PFS-6 M. 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-6 M 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-6 M of 28%. TRIAL REGISTRATION NUMBER: (1) Local ethics board approval - HREBA cc 20–0402. (2) Clinicaltrials.gov - NCT04677049. Registered 15 Dec 2020.
Research Insights
Interim analysis by central radiology review reported PFS-6 M of 82.3% (CI95% 82.14–82.46%). The interim analysis already showed an absolute increase in PFS-6 M of 28%.
- Effect
- Beneficial
- Effect size
- Large
- Dose
- 500–3000 mg/day (Phase I), 2000 mg/day ongoing RP2D
Adverse Events Reported
The most common side effect was flushing (10/15; 9 grade 1).
- Finding
- Reported
- Grade
- mild
Two DLTs occurred at 2,500 mg/d niacin (grade 3 thrombocytopenia and hyperbilirubinemia).
- Finding
- Reported
- Severity
- Serious adverse event
- Magnitude
- Two DLTs occurred at 2,500 mg/d niacin (grade 3 thrombocytopenia and hyperbilirubinemia).
Two DLTs occurred at 2,500 mg/d niacin (grade 3 thrombocytopenia and hyperbilirubinemia).
- Finding
- Reported
- Severity
- Serious adverse event
- Magnitude
- Two DLTs occurred at 2,500 mg/d niacin (grade 3 thrombocytopenia and hyperbilirubinemia).