A Phase 3, Open-label, Randomized 2-arm Study Comparing the Clinical Efficacy and Safety of Niraparib With Temozolomide in Adult Participants With Newly-diagnosed, MGMT Unmethylated Glioblastoma

Ivy Brain Tumor Center181 sites in 5 countries450 target enrollmentJune 19, 2024

ConditionsGlioblastoma GBM Brain Neoplasms, Adult, Malignant Brain Tumor

InterventionsNiraparib Temozolomide

DrugsNiraparib Temozolomide

Overview

Phase: Phase 3
Intervention: Niraparib
Conditions: Glioblastoma
Sponsor: Ivy Brain Tumor Center
Enrollment: 450
Locations: 181
Primary Endpoint: Overall survival
Status: Recruiting
Last Updated: last month

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials Related News

Overview

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

Registry

clinicaltrials.gov

Start Date

June 19, 2024

End Date

March 1, 2028

Last Updated

last month

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Ivy Brain Tumor Center

Responsible Party

Sponsor

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 pregnant, planning to get pregnant, or breastfeeding and one of the following conditions apply: is of nonchildbearing potential or is of childbearing potential AND using a contraceptive method that is highly effective (with a failure rate of \<1% per year) from screening through at least 180 days after the last dose of study intervention. Breastfeeding is contraindicated during the study and for one month after the last dose of study intervention.
•8\. Male participants: Must agree to the following during the study intervention period and for at least 6 months after the last dose of study intervention: refrain from donation sperm PLUS be abstinent from heterosexual activity or agree to use a male condom and be advised of the benefit for a female partner to use a contraceptive method that is highly effective (with a failure rate of \<1% per year).
•9\. The participant must be capable of providing signed informed consent, including compliance with the requirements and restrictions listed in the ICF and in this protocol.
•10\. Karnofsky performance status of ≥

Exclusion Criteria

•1\. Presence of metastatic or predominant leptomeningeal disease.
•2\. Current active pneumonitis or any history of pneumonitis requiring steroids (any dose) or immunomodulatory treatment within 90 days of planned start of the study.
•3\. Participant is at an increased bleeding risk due to concurrent conditions (e.g., major injuries or major surgery within the past 28 days prior to start of study treatment with the exception of tumor resection).
•4\. Any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach and/or bowels.
•5\. Has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, or persistent jaundice. NOTE: Stable noncirrhotic chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones), hepatobiliary involvement of malignancy, or chronic stable HBV infection (in a participant for whom HDV infection has been excluded) or chronic HCV infection is acceptable if the participant otherwise meets entry criteria.
•6\. Known human immunodeficiency virus (HIV) unless participants meet all of the following criteria:
•Cluster of differentiation 4 ≥350/µL and viral load \<400 copies/mL.
•No history of acquired immunodeficiency syndrome-defining opportunistic infections within 12 months prior to enrollment.
•No history of HIV-associated malignancy for the past 5 years.
•Concurrent antiretroviral therapy as per the most current National Institutes of Health (NIH) Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV \[NIH, 2021\] started \>4 weeks prior to study enrollment.

Arms & Interventions

Arm A: Niraparib

Intervention: Niraparib

Arm B: Temozolomide

Intervention: Temozolomide

Outcomes

Primary Outcomes

Overall survival

Time Frame: 24 months

Overall survival, defined as the time from the date of randomization to the date of death due to any cause.

Secondary Outcomes

Compare symptoms, function, and Health-related quality of life (HRQoL) and symptoms by EORTC QLQ-C30-item Core module (EORTC QLQ-C30) (Scores on a scale)(on Day 1 pre-dose or up to 7 days prior, on any day during the 6th week of RT, and on days of MRI at 4- and 12- weeks after RT, every 16 weeks thereafter on days of MRI)
Overall response rate(24 months)
Compare symptoms, function, and Health-related quality of life (HRQoL) and symptoms by EORTC QLQ-BN20-item Core module (EORTC QLQ-BN20) (Scores on a scale)(on Day 1 pre-dose or up to 7 days prior, on any day during the 6th week of RT, and on days of MRI at 4- and 12- weeks after RT, every 16 weeks thereafter on days of MRI)
Changes from baseline in neurocognitive function assessed by Controlled Oral Word Association(on Day 1 pre-dose or up to 7 days prior, on any day during the 6th week of RT, and on days of MRI at 4- and 12- weeks after RT, every 16 weeks thereafter on days of MRI)
Changes from baseline in neurocognitive function assessed by Trail Making Test Parts A and B(on Day 1 pre-dose or up to 7 days prior, on any day during the 6th week of RT, and on days of MRI at 4- and 12- weeks after RT, every 16 weeks thereafter on days of MRI)
Frequency and severity of symptomatic AEs based on PRO-CTCAE(24 months)
Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR)(24 months)
Compare symptoms, function, and Health-related quality of life (HRQoL) and symptoms by EQ-5D-3L(on Day 1 pre-dose or up to 7 days prior, on any day during the 6th week of RT, and on days of MRI at 4- and 12- weeks after RT, every 16 weeks thereafter on days of MRI)
Changes from baseline in neurocognitive function assessed by Hopkins Verbal Learning test(on Day 1 pre-dose or up to 7 days prior, on any day during the 6th week of RT, and on days of MRI at 4- and 12- weeks after RT, every 16 weeks thereafter on days of MRI)
Incidence of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs)(24 months)
Incidence of treatment discontinuations, dose interruptions, and dose reductions due to AEs, SAEs, or AESIs, changes in Karnofsky performance status, changes in clinical laboratory results, and vital sign measurements(24 months)