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Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
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Register:
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ClinicalTrials.gov |
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Last refreshed on:
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6 May 2024 |
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Main ID: |
NCT06388733 |
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Date of registration:
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24/04/2024 |
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Prospective Registration:
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Yes |
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Primary sponsor: |
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Public title:
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A Study Comparing Niraparib With Temozolomide in Adult Participants With Newly-diagnosed, MGMT Unmethylated Glioblastoma
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Scientific title:
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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 |
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Date of first enrolment:
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June 2024 |
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Target sample size:
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450 |
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Recruitment status: |
Not yet recruiting |
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URL:
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https://clinicaltrials.gov/ct2/show/NCT06388733 |
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Study type:
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Interventional |
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Study design:
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Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
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Phase:
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Phase 3
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Contacts
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Name:
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Nader Sanai, MD |
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Address:
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Telephone:
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Email:
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Affiliation:
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Ivy Brain Tumor Center |
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Name:
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Study Navigator |
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Address:
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Telephone:
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602-406-8605 |
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Email:
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research@ivybraintumorcenter.org |
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Affiliation:
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Key inclusion & exclusion criteria
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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.
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.
Age minimum:
18 Years
Age maximum:
N/A
Gender:
All
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Health Condition(s) or Problem(s) studied
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Brain Neoplasms, Adult, Malignant
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Glioblastoma
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Brain Tumor
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GBM
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Intervention(s)
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Drug: Temozolomide
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Drug: Niraparib
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Primary Outcome(s)
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Overall survival
[Time Frame: 24 months]
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Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR)
[Time Frame: 24 months]
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Secondary Outcome(s)
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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)
[Time Frame: 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]
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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)
[Time Frame: 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]
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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
[Time Frame: 24 months]
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Changes from baseline in neurocognitive function assessed by Trail Making Test Parts A and B
[Time Frame: 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]
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Changes from baseline in neurocognitive function assessed by Controlled Oral Word Association
[Time Frame: 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]
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Changes from baseline in neurocognitive function assessed by Hopkins Verbal Learning Test
[Time Frame: 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]
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Overall response rate
[Time Frame: 24 months]
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Number of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs)
[Time Frame: 24 months]
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Frequency and severity of symptomatic AEs based on PRO-CTCAE
[Time Frame: 24 months]
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Secondary ID(s)
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IVY P3-24-021
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Source(s) of Monetary Support
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Please refer to primary and secondary sponsors
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Results
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Results available:
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Date Posted:
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Date Completed:
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URL:
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