A Study Comparing Niraparib With Temozolomide in Adult Participants With Newly-diagnosed, MGMT Unmethylated Glioblastoma
NCT ID: NCT06388733
Last Updated: 2025-11-13
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE3
450 participants
INTERVENTIONAL
2024-06-19
2028-03-31
Brief Summary
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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
Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm A: Niraparib
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
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.
Interventions
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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
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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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.
18 Years
ALL
No
Sponsors
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GlaxoSmithKline
INDUSTRY
Ivy Brain Tumor Center
OTHER
Responsible Party
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Principal Investigators
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Nader Sanai, MD
Role: STUDY_CHAIR
Ivy Brain Tumor Center
Locations
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University of Alabama at Birmingham
Birmingham, Alabama, United States
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
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
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
Thomas Jefferson University
Philadelphia, Pennsylvania, United States
Baylor Scott & White Health
Temple, Texas, United States
The University of Vermont Medical Center
Burlington, Vermont, United States
University of Washington Medical Center
Seattle, Washington, United States
University of Wisconsin Cancer Center
Madison, Wisconsin, United States
St Vincent's Hospital Melbourne
Fitzroy, Victoria, Australia
Peter MacCallum Cancer Centre
Melbourne, Victoria, Australia
The Alfred Hospital
Melbourne, Victoria, Australia
BC Cancer - Vancouver
Vancouver, British Columbia, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
University Health Network - Princess Margaret Cancer Centre
Toronto, Ontario, Canada
CHUM (Centre hospitalier de l'Université de Montréal)
Montreal, Quebec, Canada
CHU Nice - Hôpital Pasteur
Nice, Alpes Maritimes, France
Hôpital de la Timone
Marseille, Bouches-du-Rhône, France
Institut du Cancer de Montpellier
Montpellier, Herault, France
CRLCC Eugene Marquis
Rennes, Ille et Vilaine, France
ICO - Site René Gauducheau
Saint-Herblain, Loire Atlantique, France
Groupe Hospitalier Pitie-Salpetriere
Paris, Paris, France
Centre Hospitalier Universitaire de Lyon-Hospices Civils de Lyon-Hopital Pierre Wertheimer
Bron, Rhone, France
Centre Leon Berard
Lyon, Rhone, France
CHU Amiens-Picardie - Site Sud
Amiens, Somme, France
Centre Georges François Leclerc
Dijon, , France
Universitaetsklinikum Heidelberg
Heidelberg, Baden-Wurttemberg, Germany
Universitaetsmedizin Mannheim
Mannheim, Baden-Wurttemberg, Germany
Universitaetsklinikum Tuebingen
Tübingen, Baden-Wurttemberg, Germany
Universitaetsklinikum Regensburg
Regensburg, Bavaria, Germany
Universitaetsklinikum Bonn AoeR
Bonn, North Rhine-Westphalia, Germany
Klinikum Chemnitz gGmbH
Chemnitz, Saxony, Germany
Universitaetsklinikum Leipzig
Leipzig, Saxony, Germany
IRCCS Istituto delle Scienze Neurologiche di Bologna
Bologna, Bologna, Italy
Azienda Ospedaliera Universitaria Careggi
Florence, Firenze, Italy
Fondazione IRCCS Istituto Neurologico Carlo Besta
Milan, Milano, Italy
Istituto Clinico Humanitas
Rozzano, Milano, Italy
A.S.L. Napoli 1 Centro Ospedale del Mare
Napoli, Napoli, Italy
IOV - Istituto Oncologico Veneto IRCCS
Padua, Padova, Italy
Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza
Rome, Roma, Italy
Maastricht UMC
Maastricht, , Netherlands
UMC Utrecht
Utrecht, , Netherlands
Oslo Universitetssykehus HF, Radiumhospitalet
Oslo, , Norway
St. Olavs Hospital Hf, Universitetssykehuset i Trondheim
Trondheim, , Norway
Hospital del Mar
Barcelona, Barcelona, Spain
Hospital Universitari Vall d'Hebron
Barcelona, Barcelona, Spain
Hospital Clinic de Barcelona
Barcelona, Barcelona, Spain
Hospital Universitario Reina Sofia
Córdoba, Córdoba, Spain
ICO Girona - Hospital Universitari de Girona Dr Josep Trueta
Girona, Girona, Spain
Hospital Universitario Ramon y Cajal
Madrid, Madrid, Spain
Hospital Universitario 12 de Octubre
Madrid, Madrid, Spain
Hospital Universitario HM Madrid Sanchinarro
Madrid, Madrid, Spain
Clinica Universidad de Navarra
Pamplona, Navarre, Spain
Hospital Clinico Universitario de Salamanca
Salamanca, Salamanca, Spain
Hospital Universitario Virgen del Rocio
Seville, Sevilla, Spain
ICO l'Hospitalet - Hospital Duran i Reynals
Barcelona, , Spain
Universitaetsspital Basel
Basel, , Switzerland
Ente Ospedaliero Cantonale
Bellinzona, , Switzerland
Inselspital - Universitaetsspital Bern
Bern, , Switzerland
Universitaetsspital Zürich
Zurich, , Switzerland
Bristol Haematology and Oncology Centre
Bristol, Avon, United Kingdom
Addenbrooke's Hospital
Cambridge, Cambridgeshire, United Kingdom
The Christie Hospital
Manchester, Greater Manchester, United Kingdom
The Clatterbridge Cancer Centre
Metropolitan Borough of Wirral, Merseyside, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, Strathclyde, United Kingdom
Queen Elizabeth Hospital
Birmingham, West Midlands, United Kingdom
Guy's Hospital
London, , United Kingdom
Countries
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Central Contacts
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Facility Contacts
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Trial Navigator
Role: primary
Sheila Medina
Role: primary
Mandy Schipp
Role: primary
Kimberly Caron
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Christian Lawlor
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Maxwell Klaiman
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Leigh Ann Murdock
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Cynthia Gifford-Hollingsworth
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Isza Parchini
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Dishank Patel
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Nadia Ranieri
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Lauren Drew
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Kate Sinn
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Diba Diba
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Mom Phat
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Tatiana De La Iglesia
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Helena Mathieu
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Graziella Garcion
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Besma Barka
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Pauline Linard
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Amira Beyoucef
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Andrea Dormann
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Yvonne Neu
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Ute Walter
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Heike Weißwange
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Joana Kömpel
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Katja Kolditz
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Stefania Bartolini
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Francesca Scavone
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Ludovica Ficchì
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Monica Bertossi
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Francesca De Felice
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Contact
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Laia Cano Serrano
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Nadina Fradera
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Lara Kindelán Segador
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Beatriz Martín García
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Inmaculada Robles Fernández
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Svenja Nef
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Silvia Longhi Butti
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Carola Keding
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Luis Kwan
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Cristina Bosoka
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Charlotte Williams
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Pembe Yesildag
Role: primary
Karen Karen
Role: primary
Other Identifiers
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IVY P3-24-021
Identifier Type: -
Identifier Source: org_study_id