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

Study Purpose

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 questions it aims to answer are: Does niraparib improve progression-free survival (PFS) compared to TMZ? 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

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion 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 and genomic analysis. If insufficient tissue is available, approval 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 laboratory manual.

- 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 90 days 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.

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).

- 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.

- 22.

Presence of known H3 mutation.

- 23.

Previous diagnosis of WHO Grade 2 or 3 glioma.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06388733
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Ivy Brain Tumor Center
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Nader Sanai, MD
Principal Investigator Affiliation	Ivy Brain Tumor Center
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other, Industry
Overall Status	Recruiting
Countries	Australia, Canada, France, Germany, Italy, Netherlands, Norway, Spain, Switzerland, United Kingdom, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Glioblastoma, GBM, Brain Neoplasms, Adult, Malignant, Brain Tumor

Arms & Interventions

Arms

Experimental: Arm A: Niraparib

Active Comparator: Arm B: Temozolomide

Interventions

Drug: - Niraparib

Participants will receive niraparib 200 mg orally once daily starting on Day 1 of RT. Following completion of RT, participants will continue niraparib adjuvant therapy orally once daily on Days 1 to 28 of each 28-day cycle until progression by BICR

Drug: - Temozolomide

Participants randomized to the comparator arm (Arm B) will receive SOC TMZ 75 mg/m2 orally once daily with RT starting on Day 1 of RT. Following completion of RT, participants will complete a 4-week rest period, and then receive adjuvant TMZ 150 to 200 mg/m2 orally once daily on Days 1 to 5 of each 28-day cycle until progression by BICR or for a maximum of 6 cycles.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

University of Alabama at Birmingham, Birmingham 4049979, Alabama 4829764

Status

Recruiting

Address

University of Alabama at Birmingham

Birmingham 4049979, Alabama 4829764, 35233

Site Contact

Cookie Policy

Main Menu

Clinical Trial Finder