A Study Comparing Niraparib With Temozolomide in Adult Participants With Newly-diagnosed, MGMT Unmethylated Glioblastoma
Trial Parameters
Brief Summary
The goal of this Phase 3 clinical trial is to compare the efficacy of niraparib versus temozolomide (TMZ) in adult participants with newly-diagnosed, MGMT unmethylated glioblastoma multiforme (GBM). The main question it aims to answer is: Does niraparib improve overall survival (OS) compared to TMZ? Participants will be randomly assigned to one of two treatment arms: niraparib or TMZ. * study drug (Niraparib) or * comparator drug (Temozolomide - which is the standard approved treatment for MGMT unmethylated glioblastoma). The study medication will be taken daily while receiving standard of care radiation therapy (RT) for 6-7 weeks. Participants may continue to take the niraparib or TMZ adjuvantly as long as the cancer does not get worse or completion of 6 cycles of treatment (TMZ). A total of 450 participants will be enrolled in the study. Participants' tasks will include: * Complete study visits as scheduled * Complete a diary to record study medication
Eligibility Criteria
Inclusion Criteria: * 1\. Histologic documentation of a newly-diagnosed intracranial GBM, per 2021 WHO classification guidelines through local pathology review. * 2\. Age ≥18 years at the time of signing informed consent. * 3\. Sufficient tissue available for retrospective central pathology review, retrospective central confirmation of MGMT promoter methylation status and genomic analysis. If insufficient tissue is available,pproval may be granted on a case-by-case basis after a review. * 4\. Unmethylated MGMT promoter region determined locally by a validated PSQ or qMS-PCR assay compliant to local regulations. Numerical cut-off for an MGMT unmethylated tumor will be defined in the protocol. * 5\. Suitability for SOC RT to 60 Gy in 30 fractions using ESTRO-EANO 'single phase' targeting approach \[Niyazi, 2023\], per investigator's judgment. * 6\. No prior treatment for GBM (including brachytherapy or BCNU wafers), other than surgical resection or biopsy. * 7\. Female participants: Not