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

NCT06388733 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: IVY P3-24-021
• Study Type: interventional
• Target: 450
• Locations: 11 countries
• Sites: 95

Brief Summary

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

Conditions

Glioblastoma; GBM; Brain Neoplasms, Adult, Malignant; Brain Tumor

Outcome Measures

Primary Outcomes (1)

• Overall survival

  Overall survival, defined as the time from the date of randomization to the date of death due to any cause.

  24 months

Secondary Outcomes (11)

• Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR)

  24 months

• Overall response rate

  24 months

• 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)

  on Day 1 pre-dose or up to 7 days prior, on any day during the 6th week of RT, and on days of MRI at 4- and 12- weeks after RT, every 16 weeks thereafter on days of MRI

• 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)

  on Day 1 pre-dose or up to 7 days prior, on any day during the 6th week of RT, and on days of MRI at 4- and 12- weeks after RT, every 16 weeks thereafter on days of MRI

• Compare symptoms, function, and Health-related quality of life (HRQoL) and symptoms by EQ-5D-3L

  on Day 1 pre-dose or up to 7 days prior, on any day during the 6th week of RT, and on days of MRI at 4- and 12- weeks after RT, every 16 weeks thereafter on days of MRI

Study Arms (2)

Arm A: Niraparib

EXPERIMENTAL

Drug: Niraparib

Arm B: Temozolomide

ACTIVE COMPARATOR

Drug: Temozolomide

Interventions

Niraparib DRUG

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

Also known as: Zejula

Arm A: Niraparib

Temozolomide DRUG

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.

Also known as: Temodar, TMZ

Arm B: Temozolomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Histologic documentation of a newly-diagnosed intracranial GBM, per 2021 WHO classification guidelines through local pathology review.
• \. Age ≥18 years at the time of signing informed consent.
• \. 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.
• \. 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.
• \. Suitability for SOC RT to 60 Gy in 30 fractions using ESTRO-EANO 'single phase' targeting approach \[Niyazi, 2023\], 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.
• \. 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.
• \. Ability to swallow oral medications whole.

You may not qualify if:

• \. Presence of metastatic or predominant leptomeningeal disease.
• \. Current active pneumonitis or any history of pneumonitis requiring steroids (any dose) or immunomodulatory treatment within 90 days of planned start of the study.
• \. 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).
• \. 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.

Sponsors & Collaborators

• Ivy Brain Tumor Center: lead
• GlaxoSmithKline: collaborator

Study Sites (95)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

RECRUITING

Ivy Brain Tumor Center

Phoenix, Arizona, 85013, United States

RECRUITING

Scripps Cancer Center

La Jolla, California, 92037, United States

RECRUITING

Moores UCSD Cancer Center

La Jolla, California, 92093, United States

RECRUITING

Smilow Cancer Hospital at Yale New Haven

Guilford, Connecticut, 06437, United States

RECRUITING

Indiana University

Indianapolis, Indiana, 46202, United States

RECRUITING

The NeuroMedical Center

Baton Rouge, Louisiana, 70809, United States

RECRUITING

MaineHealth Maine Medical Center Care

South Portland, Maine, 04106, United States

RECRUITING

Tufts Medical Center

Boston, Massachusetts, 02111, United States

RECRUITING

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

RECRUITING

Allina Health

Minneapolis, Minnesota, 55407, United States

RECRUITING

University of Minnesota Health Clinics and Surgery Center, Minneapolis

Minneapolis, Minnesota, 55455, United States

RECRUITING

Saint Lukes Neuro Oncology

Kansas City, Missouri, 64111, United States

RECRUITING

Washington University, School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Jersey Shore University Medical Center

Neptune City, New Jersey, 07753, United States

RECRUITING

Atlantic Health System

Summit, New Jersey, 07901, United States

RECRUITING

Northwell Health

New Hyde Park, New York, 11042, United States

RECRUITING

New York University Ambulatory Care Center

New York, New York, 10016, United States

RECRUITING

Montefiore Medical Center

The Bronx, New York, 10461, United States

RECRUITING

Duke Cancer Center Brain Tumor Clinic

Durham, North Carolina, 27710, United States

RECRUITING

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

RECRUITING

University of Cincinnati Cancer Institute

Cincinnati, Ohio, 45267, United States

RECRUITING

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

RECRUITING

The Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

Providence Portland Medical Center

Portland, Oregon, 97213, United States

RECRUITING

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

University of Pittsburgh Medical Center Health System

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Medical University of South Carolina - Department of Neurosurgery

Charleston, South Carolina, 29425, United States

RECRUITING

Baylor Scott & White Health

Temple, Texas, 76508, United States

RECRUITING

The University of Vermont Medical Center

Burlington, Vermont, 05401, United States

RECRUITING

University of Washington Medical Center

Seattle, Washington, 98109, United States

RECRUITING

University of Wisconsin Cancer Center

Madison, Wisconsin, 53706, United States

RECRUITING

St Vincent's Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

RECRUITING

Austin Health

Heidelberg, Victoria, 3084, Australia

RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

RECRUITING

Bayside Health (formerly The Alfred Hospital)

Melbourne, Victoria, 3004, Australia

RECRUITING

BC Cancer - Vancouver

Vancouver, British Columbia, V5Z 4E6, Canada

RECRUITING

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

University Health Network - Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

CHUM (Centre hospitalier de l'Université de Montréal)

Montreal, Quebec, H2X 0C1, Canada

RECRUITING

Centre Hospitalier Universitaire de Sherbrooke

Sherbrooke, Quebec, J1H 5N4, Canada

RECRUITING

CHU Nice - Hôpital Pasteur

Nice, Alpes Maritimes, 06001, France

RECRUITING

Hôpital de la Timone

Marseille, Bouches-du-Rhône, 13385, France

RECRUITING

Institut du Cancer de Montpellier

Montpellier, Herault, 34298, France

RECRUITING

CRLCC Eugene Marquis

Rennes, Ille et Vilaine, 35000, France

RECRUITING

ICO - Site René Gauducheau

Saint-Herblain, Loire Atlantique, 44800, France

RECRUITING

Groupe Hospitalier Pitie-Salpetriere

Paris, Paris, 75013, France

RECRUITING

Centre Hospitalier Universitaire de Lyon-Hospices Civils de Lyon-Hopital Pierre Wertheimer

Bron, Rhone, 69500, France

RECRUITING

Centre Leon Berard

Lyon, Rhone, 69008, France

RECRUITING

CHU Amiens-Picardie - Site Sud

Amiens, Somme, 80054, France

RECRUITING

Centre Georges François Leclerc

Dijon, 21079, France

RECRUITING

Universitaetsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

RECRUITING

Universitaetsmedizin Mannheim

Mannheim, Baden-Wurttemberg, 68167, Germany

RECRUITING

Universitaetsklinikum Tuebingen

Tübingen, Baden-Wurttemberg, 72076, Germany

RECRUITING

Universitaetsklinikum Regensburg

Regensburg, Bavaria, 93053, Germany

RECRUITING

Universitaetsklinikum Bonn AoeR

Bonn, North Rhine-Westphalia, 53127, Germany

RECRUITING

Klinikum Chemnitz gGmbH

Chemnitz, Saxony, 09116, Germany

RECRUITING

Universitaetsklinikum Leipzig

Leipzig, Saxony, 04103, Germany

RECRUITING

Vivantes Klinikum Neukoelln

Berlin, State of Berlin, 12351, Germany

RECRUITING

IRCCS Istituto delle Scienze Neurologiche di Bologna

Bologna, Bologna, 40139, Italy

RECRUITING

Azienda Ospedaliera Universitaria Careggi

Florence, Firenze, 50134, Italy

RECRUITING

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, Milano, 20133, Italy

RECRUITING

Istituto Clinico Humanitas

Rozzano, Milano, 20089, Italy

RECRUITING

A.S.L. Napoli 1 Centro Ospedale del Mare

Naples, Napoli, 80147, Italy

RECRUITING

IOV - Istituto Oncologico Veneto IRCCS

Padua, Padova, 35128, Italy

RECRUITING

Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza

Rome, Roma, 00161, Italy

RECRUITING

Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino

Torino, Torino, 10124, Italy

RECRUITING

Maastricht UMC

Maastricht, 6229 HX, Netherlands

RECRUITING

UMC Utrecht

Utrecht, 3584 CX, Netherlands

RECRUITING

Oslo Universitetssykehus HF, Radiumhospitalet

Oslo, 0379, Norway

RECRUITING

St. Olavs Hospital Hf, Universitetssykehuset i Trondheim

Trondheim, 7030, Norway

RECRUITING

Hospital del Mar

Barcelona, Barcelona, 08003, Spain

RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona, 08035, Spain

RECRUITING

Hospital Clinic de Barcelona

Barcelona, Barcelona, 08036, Spain

RECRUITING

Hospital Universitario Reina Sofia

Córdoba, Córdoba, 14004, Spain

RECRUITING

ICO Girona - Hospital Universitari de Girona Dr Josep Trueta

Girona, Girona, 17007, Spain

RECRUITING

Hospital Universitario Ramon y Cajal

Madrid, Madrid, 28034, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, Madrid, 28041, Spain

RECRUITING

Hospital Universitario HM Madrid Sanchinarro

Madrid, Madrid, 28050, Spain

RECRUITING

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

RECRUITING

Hospital Clinico Universitario de Salamanca

Salamanca, Salamanca, 37370, Spain

RECRUITING

Hospital Universitario Virgen del Rocio

Seville, Sevilla, 41013, Spain

RECRUITING

ICO l'Hospitalet - Hospital Duran i Reynals

Barcelona, 08906, Spain

RECRUITING

Universitaetsspital Basel

Basel, 4031, Switzerland

RECRUITING

Ente Ospedaliero Cantonale

Bellinzona, 6500, Switzerland

RECRUITING

Inselspital - Universitaetsspital Bern

Bern, 3010, Switzerland

RECRUITING

Universitaetsspital Zürich

Zurich, 8091, Switzerland

RECRUITING

Bristol Haematology and Oncology Centre

Bristol, Avon, BS2 8ED, United Kingdom

RECRUITING

Addenbrooke's Hospital

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

RECRUITING

The Christie Hospital

Manchester, Greater Manchester, M20 4BX, United Kingdom

RECRUITING

The Clatterbridge Cancer Centre

Metropolitan Borough of Wirral, Merseyside, CH63 4JY, United Kingdom

RECRUITING

Velindre Cancer Centre

Cardiff, South Glamorgan, CF14 2TL, United Kingdom

RECRUITING

Beatson West of Scotland Cancer Centre

Glasgow, Strathclyde, G12 0YN, United Kingdom

RECRUITING

Queen Elizabeth Hospital

Birmingham, West Midlands, B15 2TH, United Kingdom

RECRUITING

Guy's Hospital

London, SE1 9RT, United Kingdom

RECRUITING

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Interventions

niraparib; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Nader Sanai, MD

  Ivy Brain Tumor Center

  STUDY CHAIR

Central Study Contacts

Study Navigator

CONTACT

602-406-8605; research@ivybraintumorcenter.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Blinded Independent Central Review is composed of independent radiologists and will be utilized to assess progression of disease
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2024
• First Posted: April 29, 2024
• Study Start: June 19, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: April 1, 2026

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (10); CA (5); NL (2); NO (2); IT (8); ES (12); GB (8); AU (4); US (32); CH (4); DE (8)