A Study Comparing Niraparib With Temozolomide in Adult Participants With Newly-diagnosed, MGMT Unmethylated Glioblastoma

Running, not enrolling · Phase 3

Conditions studied: Glioblastoma, GBM, Brain Neoplasms, Adult, Malignant, Brain Tumor

In brief

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

Key facts

Study ID

NCT06388733

Run by

Ivy Brain Tumor Center

People needed

450

Starts

2024-06-19

Expected to finish

2028-03-01

Last updated by the study team

2026-07-01

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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 ≥70.
• 11. Adequate organ function
• 12. Normal blood pressure (BP) or adequately treated and controlled hypertension (defined as systolic BP ≤140 mmHg and diastolic BP ≤90 mmHg).
• 13. Stable or decreased dose of dexamethasone, requiring no more than 5 mg daily equivalent dose, within 7 days before randomization.
• 14. Ability to swallow oral medications whole.

You may not qualify if…

• 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.
• 7. MDS/AML or with features suggestive of MDS/AML.
• 8. History of another malignancy within 2 years prior to registration. Participants with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder are eligible. Participants with a history of other malignancies are eligible if they have been treated with curative intent or continuously disease free for at least 2 years after definitive primary treatment.
• 9. Prior history of posterior reversible encephalopathy syndrome (PRES).
• 10. Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study requirements and/or follow-up procedures.
• 11. Inability to undergo MRI brain with IV contrast.
• 12. Biopsy and/or resection (whichever is later) occurring >6 weeks prior to planned RT start date.
• 13. Surgical wound complication recovery at the time of enrollment.
• 14. Known hypersensitivity to the components of niraparib, TMZ, or their formulation excipients.
• 15. Known hypersensitivity to dacarbazine (DTIC).
• 16. Prior therapy with PARP inhibitors for systemic cancer.
• 17. Received a live vaccine within 30 days before the planned start of study intervention. Coronavirus disease 2019 (COVID-19) vaccines that do not contain live viruses are allowed. Note: mRNA and adenoviral-based COVID-19 vaccines are considered non-live.
• 18. Received a transfusion (platelets or red blood cells) or colony-stimulating factors (e.g., granulocyte macrophage colony-stimulating factor or recombinant erythropoietin) within 4 weeks of the planned start of study intervention.
• 19. Treatment with another investigational drug or other intervention within 5 half-lives of the investigational product.
• 20. Treatment with tumor treating fields (e.g., Optune) for GBM.
• 21. Presence of known isocitrate dehydrogenase (IDH) mutation.

Where it is running

• Ivy Brain Tumor Center — Phoenix, Arizona, United States
• Scripps Cancer Center — La Jolla, California, United States
• Moores UCSD Cancer Center — La Jolla, California, United States
• Smilow Cancer Hospital at Yale New Haven — Guilford, Connecticut, United States
• Indiana University — Indianapolis, Indiana, United States
• The NeuroMedical Center — Baton Rouge, Louisiana, United States
• MaineHealth Maine Medical Center Care — South Portland, Maine, United States
• Tufts Medical Center — Boston, Massachusetts, United States
• University of Michigan Rogel Cancer Center — Ann Arbor, Michigan, United States
• Allina Health — Minneapolis, Minnesota, United States
• University of Minnesota Health Clinics and Surgery Center, Minneapolis — Minneapolis, Minnesota, United States
• Saint Lukes Neuro Oncology — Kansas City, Missouri, United States
• Washington University, School of Medicine — St Louis, Missouri, United States
• Jersey Shore University Medical Center — Neptune City, New Jersey, United States
• Atlantic Health System — Summit, New Jersey, United States
• Northwell Health — New Hyde Park, New York, United States
• New York University Ambulatory Care Center — New York, New York, United States
• Montefiore Medical Center — The Bronx, New York, United States
• Duke Cancer Center Brain Tumor Clinic — Durham, North Carolina, United States
• Wake Forest Baptist Health — Winston-Salem, North Carolina, United States
• University of Cincinnati Cancer Institute — Cincinnati, Ohio, United States
• The Cleveland Clinic Foundation — Cleveland, Ohio, United States
• The Ohio State University — Columbus, Ohio, United States
• Providence Portland Medical Center — Portland, Oregon, United States
• University of Alabama at Birmingham — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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