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A study comparing niraparib with temozolomide in adult participants with newly-diagnosed, MGMT unmethylated glioblastoma
EU CTIS ID: 2024-513077-48-00
What this study is testing
Test whether niraparib compared with temozolomide significantly extends overall survival in participants with newly-diagnosed, MGMT promoter unmethylated glioblastoma
- Therapeutic confirmatory (Phase III)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Histologic documentation of a newly-diagnosed intracranial GBM, per 2021 WHO classification guidelines through local pathology review.
- Karnofsky performance status of ≥70.
- Adequate organ function
- Normal blood pressure (BP) or adequately treated and controlled hypertension (defined as systolic BP ≤140 mmHg and diastolic BP ≤90 mmHg).
- Stable or decreased dose of dexamethasone, requiring no more than 5 mg daily equivalent dose, within 7 days before randomization. Participants on other corticosteroids must not exceed an equivalent dose. .
- Ability to swallow oral medications whole.
You likely can't join if
- Presence of metastatic or predominant leptomeningeal disease.
- Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study requirements and/or follow-up procedures.
- Inability to undergo MRI brain with IV contrast.
- Biopsy and/or resection (whichever is later) occurring >6 weeks prior to planned RT start date.
- Surgical wound complication recovery at the time of enrollment.
- Known hypersensitivity to the components of niraparib, TMZ, or their formulation excipients.
See the full eligibility criteria
Who can join
- Histologic documentation of a newly-diagnosed intracranial GBM, per 2021 WHO classification guidelines through local pathology review.
- Karnofsky performance status of ≥70.
- Adequate organ function
- Normal blood pressure (BP) or adequately treated and controlled hypertension (defined as systolic BP ≤140 mmHg and diastolic BP ≤90 mmHg).
- Stable or decreased dose of dexamethasone, requiring no more than 5 mg daily equivalent dose, within 7 days before randomization. Participants on other corticosteroids must not exceed an equivalent dose. .
- Ability to swallow oral medications whole.
- Age ≥18 years at the time of signing informed consent.
- 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.
- 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 as defined in the protocol.
- Suitability for SOC RT to 60 Gy in 30 fractions using ESTRO-EANO 'single phase' targeting approach, per investigator's judgment.
- No prior treatment for GBM (including brachytherapy or BCNU wafers), other than surgical resection or biopsy.
- 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.
- 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).
- 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.
What rules you out
- Presence of metastatic or predominant leptomeningeal disease.
- Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study requirements and/or follow-up procedures.
- Inability to undergo MRI brain with IV contrast.
- Biopsy and/or resection (whichever is later) occurring >6 weeks prior to planned RT start date.
- Surgical wound complication recovery at the time of enrollment.
- Known hypersensitivity to the components of niraparib, TMZ, or their formulation excipients.
- Known hypersensitivity to dacarbazine (DTIC).
- Prior therapy with PARP inhibitors for systemic cancer.
- 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.
- 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.
- Treatment with another investigational drug or other intervention within 5 half-lives of the investigational product.
- Current active pneumonitis or any history of pneumonitis requiring steroids (any dose) or immunomodulatory treatment within 90 days of planned start of the study.
- Treatment with tumor treating fields (e.g., Optune) for GBM.
- Presence of known isocitrate dehydrogenase (IDH) mutation.
- Presence of known H3 mutation.
- Previous diagnosis of WHO Grade 2 or 3 glioma.
- 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)
- Any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach and/or bowels.
- 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.
- 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.
- MDS/AML or with features suggestive of MDS/AML.
- 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.
- Prior history of posterior reversible encephalopathy syndrome (PRES).
The study team makes the final eligibility decision.
Where it's taking place
- Australia
- United Kingdom
- United States
- Canada
- Switzerland
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Australia; United Kingdom; United States; Canada; Switzerland. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.