Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06388733




Registration number
NCT06388733
Ethics application status
Date submitted
24/04/2024
Date registered
29/04/2024
Date last updated
17/08/2025

Titles & IDs
Public title
A Study Comparing Niraparib With Temozolomide in Adult Participants With Newly-diagnosed, MGMT Unmethylated Glioblastoma
Scientific title
A 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
Secondary ID [1] 0 0
IVY P3-24-021
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glioblastoma 0 0
GBM 0 0
Brain Neoplasms, Adult, Malignant 0 0
Brain Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Niraparib
Treatment: Drugs - Temozolomide

Experimental: Arm A: Niraparib -

Active comparator: Arm B: Temozolomide -


Treatment: Drugs: 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

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR)
Timepoint [1] 0 0
24 months
Primary outcome [2] 0 0
Overall survival
Timepoint [2] 0 0
24 months
Secondary outcome [1] 0 0
Overall response rate
Timepoint [1] 0 0
24 months
Secondary outcome [2] 0 0
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)
Timepoint [2] 0 0
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
Secondary outcome [3] 0 0
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)
Timepoint [3] 0 0
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
Secondary outcome [4] 0 0
Changes from baseline in neurocognitive function assessed by Hopkins Verbal Learning Test
Timepoint [4] 0 0
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
Secondary outcome [5] 0 0
Changes from baseline in neurocognitive function assessed by Controlled Oral Word Association
Timepoint [5] 0 0
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
Secondary outcome [6] 0 0
Changes from baseline in neurocognitive function assessed by Trail Making Test Parts A and B
Timepoint [6] 0 0
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
Secondary outcome [7] 0 0
Number of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs)
Timepoint [7] 0 0
24 months
Secondary outcome [8] 0 0
Number 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
Timepoint [8] 0 0
24 months
Secondary outcome [9] 0 0
Frequency and severity of symptomatic AEs based on PRO-CTCAE
Timepoint [9] 0 0
24 months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/06/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2028
Actual
Sample size
Target
450
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [2] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Louisiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Maine
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Vermont
Country [11] 0 0
United States of America
State/province [11] 0 0
Washington
Country [12] 0 0
United States of America
State/province [12] 0 0
Wisconsin
Country [13] 0 0
France
State/province [13] 0 0
Alpes Maritimes
Country [14] 0 0
France
State/province [14] 0 0
Bouches-du-Rhône
Country [15] 0 0
France
State/province [15] 0 0
Herault
Country [16] 0 0
France
State/province [16] 0 0
Loire Atlantique
Country [17] 0 0
France
State/province [17] 0 0
Paris
Country [18] 0 0
France
State/province [18] 0 0
Rhone
Country [19] 0 0
France
State/province [19] 0 0
Somme
Country [20] 0 0
France
State/province [20] 0 0
Dijon
Country [21] 0 0
Germany
State/province [21] 0 0
Baden-Wurttemberg
Country [22] 0 0
Germany
State/province [22] 0 0
North Rhine-Westphalia
Country [23] 0 0
Germany
State/province [23] 0 0
Saxony
Country [24] 0 0
Italy
State/province [24] 0 0
Bologna
Country [25] 0 0
Italy
State/province [25] 0 0
Firenze
Country [26] 0 0
Italy
State/province [26] 0 0
Milano
Country [27] 0 0
Netherlands
State/province [27] 0 0
Maastricht
Country [28] 0 0
Netherlands
State/province [28] 0 0
Utrecht
Country [29] 0 0
Norway
State/province [29] 0 0
Oslo
Country [30] 0 0
Spain
State/province [30] 0 0
Barcelona
Country [31] 0 0
Spain
State/province [31] 0 0
Córdoba
Country [32] 0 0
Spain
State/province [32] 0 0
Girona
Country [33] 0 0
Spain
State/province [33] 0 0
Madrid
Country [34] 0 0
Spain
State/province [34] 0 0
Navarre
Country [35] 0 0
Spain
State/province [35] 0 0
Sevilla
Country [36] 0 0
United Kingdom
State/province [36] 0 0
Greater Manchester
Country [37] 0 0
United Kingdom
State/province [37] 0 0
Merseyside

Funding & Sponsors
Primary sponsor type
Other
Name
Ivy Brain Tumor Center
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
GlaxoSmithKline
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Nader Sanai, MD
Address 0 0
Ivy Brain Tumor Center
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Study Navigator
Address 0 0
Country 0 0
Phone 0 0
602-406-8605
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT06388733