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

Recruitment Status
ACTIVE, NOT RECRUITING
(See Contacts and Locations)Verified May 2026 by Ivy Brain Tumor Center
Sponsor
Ivy Brain Tumor Center
Information Provided by (Responsible Party)
Ivy Brain Tumor Center
Clinicaltrials.gov Identifier
NCT06388733
Other Study ID Numbers:
IVY P3-24-021
First Submitted
April 23, 2024
First Posted
April 28, 2024
Last Update Posted
June 30, 2026
Last Verified
May 2026

ClinicalTrials.gov processed this data on June 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
GlioblastomaGBMBrain Neoplasms, Adult, MalignantBrain Tumor
Drug: NiraparibDrug: Temozolomide

Study Design

Study TypeInterventional
Actual Enrollment450 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitleA 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
Study Start DateJune 18, 2024
Actual Primary Completion Date1yr 3mos from now
Actual Study Completion Date1yr 6mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Arm A: Niraparib
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
Arm B: Temozolomide
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.

Outcome Measures

Primary Outcome Measures
  1. Overall survival
    Overall survival, defined as the time from the date of randomization to the date of death due to any cause.
Secondary Outcome Measures
  1. Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR)
    Progression-free survival, defined as the time from the date of randomization to the date of first disease progression per RANO 2.0 by BICR assessment or death from any cause, whichever occurs first.
  2. Overall response rate
    Percentage of patients who achieved confirmed complete response or confirmed partial response to treatment evaluated using RANO 2.0 by BICR.
  3. 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)
    EORTC QLQ-C30 is a validated questionnaire to assess overall health-related quality of life in participants with cancer.
  4. 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)
    EORTC QLQ-BN20 is a clinically valid and useful tool for assessing disease- and treatment-specific symptoms in brain neoplasm participants.
  5. Compare symptoms, function, and Health-related quality of life (HRQoL) and symptoms by EQ-5D-3L
    The EQ-5D-3L descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression.
  6. Changes from baseline in neurocognitive function assessed by Hopkins Verbal Learning test
    The Hopkins Verbal Learning Test is designed to evaluate memory. It requires participants to memorize a list of 12 items for 3 consecutive tests (recall), to identify the same 12 items from a list of semantically related or unrelated items (recognition), and to recall the same 12 items after a 15-minute delay (delayed recall).
  7. Changes from baseline in neurocognitive function assessed by Controlled Oral Word Association
    The Controlled Oral Word Association Test is designed to evaluate verbal fluency. It requires participants to name words beginning with a specific letter with increasing associated activity, in 3 one-minute periods.
  8. Changes from baseline in neurocognitive function assessed by Trail Making Test Parts A and B
    The Trail Making Test Part A is designed to evaluate visual motor scanning speed, and the Trail Making Test Part B is designed to evaluate executive function. These tests require participants to connect circles in numerical (Part A) or alternating numerical and alphabetical sequence (Part B) within a timed interval of less than 5 minutes for each test.
  9. Incidence of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs)
    AEs, SAEs and AESIs will be collected
  10. 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
    Treatment discontinuations, dose interruptions, and dose reductions
  11. Frequency and severity of symptomatic AEs based on PRO-CTCAE
    The PRO-CTCAE is a patient-reported outcome measure developed to evaluate symptomatic toxicity in patients on cancer clinical trials.

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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 ≥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 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.
22\. Presence of known H3 mutation.
23\. Previous diagnosis of WHO Grade 2 or 3 glioma.

Contacts and Locations

Sponsors and CollaboratorsIvy Brain Tumor Center
Locations
University of Alabama at Birmingham | Birmingham Alabama, United States, 35233Ivy Brain Tumor Center | Phoenix Arizona, United States, 85013Scripps Cancer Center | La Jolla California, United States, 92037Moores UCSD Cancer Center | La Jolla California, United States, 92093Smilow Cancer Hospital at Yale New Haven | Guilford Connecticut, United States, 06437Indiana University | Indianapolis Indiana, United States, 46202The NeuroMedical Center | Baton Rouge Louisiana, United States, 70809MaineHealth Maine Medical Center Care | South Portland Maine, United States, 04106Tufts Medical Center | Boston Massachusetts, United States, 02111University of Michigan Rogel Cancer Center | Ann Arbor Michigan, United States, 48109Allina Health | Minneapolis Minnesota, United States, 55407University of Minnesota Health Clinics and Surgery Center, Minneapolis | Minneapolis Minnesota, United States, 55455Saint Lukes Neuro Oncology | Kansas City Missouri, United States, 64111Washington University, School of Medicine | St Louis Missouri, United States, 63110Jersey Shore University Medical Center | Neptune City New Jersey, United States, 07753Atlantic Health System | Summit New Jersey, United States, 07901Northwell Health | New Hyde Park New York, United States, 11042New York University Ambulatory Care Center | New York New York, United States, 10016Montefiore Medical Center | The Bronx New York, United States, 10461Duke Cancer Center Brain Tumor Clinic | Durham North Carolina, United States, 27710Wake Forest Baptist Health | Winston-Salem North Carolina, United States, 27157University of Cincinnati Cancer Institute | Cincinnati Ohio, United States, 45267The Cleveland Clinic Foundation | Cleveland Ohio, United States, 44195The Ohio State University | Columbus Ohio, United States, 43210Providence Portland Medical Center | Portland Oregon, United States, 97213Thomas Jefferson University | Philadelphia Pennsylvania, United States, 19107University of Pittsburgh Medical Center Health System | Pittsburgh Pennsylvania, United States, 15232Medical University of South Carolina - Department of Neurosurgery | Charleston South Carolina, United States, 29425Baylor Scott & White Health | Temple Texas, United States, 76508The University of Vermont Medical Center | Burlington Vermont, United States, 05401University of Washington Medical Center | Seattle Washington, United States, 98109University of Wisconsin Cancer Center | Madison Wisconsin, United States, 53706St Vincent's Hospital Melbourne | Fitzroy Victoria, Australia, 3065Austin Health | Heidelberg Victoria, Australia, 3084Peter MacCallum Cancer Centre | Melbourne Victoria, Australia, 3000Bayside Health (formerly The Alfred Hospital) | Melbourne Victoria, Australia, 3004BC Cancer - Vancouver | Vancouver British Columbia, Canada, V5Z 4E6Sunnybrook Health Sciences Centre | Toronto Ontario, Canada, M4N 3M5University Health Network - Princess Margaret Cancer Centre | Toronto Ontario, Canada, M5G 2M9CHUM (Centre hospitalier de l'Université de Montréal) | Montreal Quebec, Canada, H2X 0C1Centre Hospitalier Universitaire de Sherbrooke | Sherbrooke Quebec, Canada, J1H 5N4CHU Nice - Hôpital Pasteur | Nice Alpes Maritimes, France, 06001Hôpital de la Timone | Marseille Bouches-du-Rhône, France, 13385Institut du Cancer de Montpellier | Montpellier Herault, France, 34298CRLCC Eugene Marquis | Rennes Ille et Vilaine, France, 35000ICO - Site René Gauducheau | Saint-Herblain Loire Atlantique, France, 44800Groupe Hospitalier Pitie-Salpetriere | Paris Paris, France, 75013Centre Hospitalier Universitaire de Lyon-Hospices Civils de Lyon-Hopital Pierre Wertheimer | Bron Rhone, France, 69500Centre Leon Berard | Lyon Rhone, France, 69008CHU Amiens-Picardie - Site Sud | Amiens Somme, France, 80054Centre Georges François Leclerc | Dijon , France, 21079Universitaetsklinikum Heidelberg | Heidelberg Baden-Wurttemberg, Germany, 69120Universitaetsmedizin Mannheim | Mannheim Baden-Wurttemberg, Germany, 68167Universitaetsklinikum Tuebingen | Tübingen Baden-Wurttemberg, Germany, 72076Universitaetsklinikum Regensburg | Regensburg Bavaria, Germany, 93053Universitaetsklinikum Bonn AoeR | Bonn North Rhine-Westphalia, Germany, 53127Klinikum Chemnitz gGmbH | Chemnitz Saxony, Germany, 09116Universitaetsklinikum Leipzig | Leipzig Saxony, Germany, 04103Vivantes Klinikum Neukoelln | Berlin State of Berlin, Germany, 12351IRCCS Istituto delle Scienze Neurologiche di Bologna | Bologna Bologna, Italy, 40139Azienda Ospedaliera Universitaria Careggi | Florence Firenze, Italy, 50134Fondazione IRCCS Istituto Neurologico Carlo Besta | Milan Milano, Italy, 20133Istituto Clinico Humanitas | Rozzano Milano, Italy, 20089A.S.L. Napoli 1 Centro Ospedale del Mare | Naples Napoli, Italy, 80147IOV - Istituto Oncologico Veneto IRCCS | Padova Padova, Italy, 35128Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza | Rome Roma, Italy, 00161Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino | Torino Torino, Italy, 10124Maastricht UMC | Maastricht , Netherlands, 6229 HXUMC Utrecht | Utrecht , Netherlands, 3584 CXOslo Universitetssykehus HF, Radiumhospitalet | Oslo , Norway, 0379St. Olavs Hospital Hf, Universitetssykehuset i Trondheim | Trondheim , Norway, 7030Hospital del Mar | Barcelona Barcelona, Spain, 08003Hospital Universitari Vall d'Hebron | Barcelona Barcelona, Spain, 08035Hospital Clinic de Barcelona | Barcelona Barcelona, Spain, 08036Hospital Universitario Reina Sofia | Córdoba Córdoba, Spain, 14004ICO Girona - Hospital Universitari de Girona Dr Josep Trueta | Girona Girona, Spain, 17007Hospital Universitario Ramon y Cajal | Madrid Madrid, Spain, 28034Hospital Universitario 12 de Octubre | Madrid Madrid, Spain, 28041Hospital Universitario HM Madrid Sanchinarro | Madrid Madrid, Spain, 28050Clinica Universidad de Navarra | Pamplona Navarre, Spain, 31008Hospital Clinico Universitario de Salamanca | Salamanca Salamanca, Spain, 37370Hospital Universitario Virgen del Rocio | Seville Sevilla, Spain, 41013ICO l'Hospitalet - Hospital Duran i Reynals | Barcelona , Spain, 08906Universitaetsspital Basel | Basel , Switzerland, 4031Ente Ospedaliero Cantonale | Bellinzona , Switzerland, 6500Inselspital - Universitaetsspital Bern | Bern , Switzerland, 3010Universitaetsspital Zürich | Zurich , Switzerland, 8091Bristol Haematology and Oncology Centre | Bristol Avon, United Kingdom, BS2 8EDAddenbrooke's Hospital | Cambridge Cambridgeshire, United Kingdom, CB2 0QQThe Christie Hospital | Manchester Greater Manchester, United Kingdom, M20 4BXThe Clatterbridge Cancer Centre | Metropolitan Borough of Wirral Merseyside, United Kingdom, CH63 4JYVelindre Cancer Centre | Cardiff South Glamorgan, United Kingdom, CF14 2TLBeatson West of Scotland Cancer Centre | Glasgow Strathclyde, United Kingdom, G12 0YNQueen Elizabeth Hospital | Birmingham West Midlands, United Kingdom, B15 2THGuy's Hospital | London , United Kingdom, SE1 9RT
Investigators
Study Chair: Nader Sanai, MD, Ivy Brain Tumor Center