GlioblastomaEarly Phase 1NCT05076513
Trial of Niraparib in Participants With Newly-diagnosed Glioblastoma and Recurrent Glioma
A Early Phase 1 study testing Niraparib and Radiation therapy in people with Glioblastoma and Glioblastoma Multiforme, run by Nader Sanai at 1 site in United States.
Trial summary
This is an open-label, multi-center Phase 0 study with an expansion phase that will enroll up to 24 participants with newly-diagnosed glioblastoma and up to 18 recurrent glioma participants with IDH mutation and ATRX loss. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Glioblastoma Multiforme, Glioma
- What is being tested?
- Niraparib and Radiation therapy
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Oct 2021to Mar 2027
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Arm A participants undergoing resection for a suspected newly diagnosed glioblastoma. For Arm B, participants undergoing resection who have had a prior resection of histologically diagnosed WHO grade II-IV glioma with IDH1 or IDH2 mutation and ATRX loss.
- Arm A participants must have measurable disease preoperatively, defined as at least 1 contrast-enhancing lesion, with 2 perpendicular measurements of at least 1 cm.
- Ability to understand and the willingness to sign a written informed consent document (personally or by the legally authorized representative, if applicable).
- Participant has voluntarily agreed to participate by giving written informed consent (personally or via legally authorized representative(s), and assent if applicable). Written informed consent for the protocol must be obtained prior to any screening procedures. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other procedures.
- Age ≥18 at time of consent
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- Have a performance status (PS) of ≤2 on the Eastern Cooperative Oncology (Group (ECOG) scale (Oken et al. 1982)
- Ability to swallow oral medications.
- Confirmed negative serum pregnancy test (β-hCG) before starting study treatment or participant who is no longer of childbearing potential due to surgical, chemical, or natural menopause. If the serum pregnancy test is completed > 7 days from Day 1, a urine pregnancy test will be done to confirm a negative result prior to Day 1 dose administration.
- For females of reproductive potential: use of highly effective contraception for at least 1 month prior to treatment and agreement to use such a method during study participation and for an additional 6 months after the end of treatment administration.
- For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner and for an additional 3 months after the end of treatment administration. Avoid sperm donation for duration of the study and for an additional 6 months after the end of treatment administration.
- Agreement to adhere to Lifestyle Considerations throughout study duration.
- Participants who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events [CTCAE] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to Day 1. A washout period of at least 21 days is required between last chemotherapy and Day 1.
- Females of child-bearing potential must agree not to breastfeed starting at screening, throughout the study period and for 6 months after final study drug administration.
- Participant has normal blood pressure or adequately treated and controlled hypertension (Defined as systolic BP ≤140 mmHg and diastolic BP ≤90 mmHg).
- Participant has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by the local laboratory for eligibility):
- Adequate Bone Marrow Function:
- Absolute Neutrophil Count ≥1,500/mcL
- Platelets (at time of surgery) ≥100,000/mcL
- Hemoglobin ≥9.0 g/dL. Participants may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.
- Adequate Hepatic Function:
- Total Bilirubin ≤1.5 X ULN. Participants with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted.
- AST(SGOT) ≤2.5 X institutional ULN
- ALT(SGPT) ≤2.5 X institutional ULN
- Adequate Renal Function:
- Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 by Chronic Disease Epidemiology Collaboration (CKD-EPI) equation
- INR ≤1.5 x ULN
Who cannot join
- Current use of coumarin-derived anticoagulant for treatment, prophylaxis or otherwise, that cannot be discontinued prior to surgery. Therapy with heparin, low molecular weight heparin (LMWH) or fondaparinux is allowed.
- Pregnancy or lactation.
- Known allergic reactions to components of the niraparib tablet, including FD\&C Yellow No. 5..
- Active infection or fever >38.5°C requiring systemic antibiotic, antifungal or antiviral therapy within 4 weeks of Day 1.
- Known to have active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and active and chronic hepatitis as determined by the investigator.
- Known active systemic bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive]. Screening is not required for enrollment.
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- Any of the following cardiovascular criteria:
- Current evidence of cardiac ischemia
- Current symptomatic pulmonary embolism
- Acute myocardial infarction ≤ 6 months prior to Day 1
- Heart failure of New York Heart Association Classification III or IV ≤ 6 months prior to Day 1 (Appendix 13.2)
- Grade ≥ 2 ventricular arrhythmia ≤ 6 months prior to Day 1
- Cerebral vascular accident (CVA) or transient ischemic attack (TIA) ≤ 6 months prior to Day 1
- Participant has myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML.
- Participant has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
- Prior therapy with PARP inhibitors at a therapeutic dose.
- Treatment with another investigational drug or other intervention within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer.
Trial locations and contacts
1 site in 1 country.
United States1 site
St. Joseph's Hospital and Medical Center
Phoenix, Arizona, 85013
About this study
Official title: A Phase 0 'Trigger' Trial of Niraparib in Newly-diagnosed Glioblastoma and Recurrent IDH1/2(+) ATRX Mutant Glioma
This is an open-label, multi-center Phase 0 study with an expansion phase that will enroll up to 24 participants with newly-diagnosed glioblastoma and up to 18 recurrent glioma participants with IDH mutation and ATRX loss. The trial will be composed of a Phase 0 component (subdivided into Arm A and B) and a therapeutic expansion phase. Patients with tumors demonstrating a positive PK Response (in Arm A) or a positive PD Response (in Arm B) of the Phase 0 component of the study will graduate to a therapeutic expansion phase that combines therapeutic dosing of niraparib plus standard-of-care fractionated radiotherapy (in Arm A) or niraparib monotherapy (in Arm B) until progression of disease.
- Conditions
- Glioblastoma, Glioblastoma Multiforme, Glioma, GBM, Glioma, Malignant, Glioblastoma Multiforme of Brain
- Being tested
- Niraparib, Radiation therapy
- Medical subject headings
- Glioblastoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NiraparibDrug
Also called Zejula
In Phase 0, 300mg administered orally QD for 4 days prior to resection.
In the Expansion cohort/Maintenance phase, niraparib will be administered as described below:
- For patients weighing <77 kg (<170 lbs) OR with a platelet count <150,000/mcL, the recommended dosage is 200 mg taken orally once daily.
- For patients weighing ≥77 kg (≥170 lbs) AND a platelet count ≥150,000/ mcL, the recommended dosage is 300 mg taken orally once daily.
Radiation therapyRadiation
Participants in Arm A who move onto the Expansion cohort will receive 6-7 weeks of radiation therapy per standard of care.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Presumed Newly-Diagnosed glioblastoma | Experimental | Participants undergoing resection for a presumed newly-diagnosed glioblastoma (WHO grade 4) will be treated with niraparib for 4 days prior to surgical resection. Participants who proceed to the therapeutic expansion phase of this study will receive niraparib in combination with radiation (60 Gy over 6-7 weeks, as per standard of care). Following radiotherapy, eligible study participants may receive niraparib maintenance treatment. Receives: Drug: Niraparib; Radiation: Radiation therapy |
| Arm B: Recurrent Glioma (Grades II-IV) | Experimental | Participants undergoing resection of a recurrent WHO Grade II, III, or IV glioma with IDH1 or IDH2 mutation and ATRX loss will be treated with niraparib for 4 days prior to a planned surgical resection. Participants who proceed to the Expansion cohort will receive niraparib in 28d cycles after surgery. Receives: Drug: Niraparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 0 Arm A: Total and unbound niraparib concentration in enhancing and nonenhancing tissue
Tumor to plasma partition coefficients of niraparib for total (Kp) and unbound (Kp,uu) drug levels
Measured: Day 4 Intra-operative sample
Phase 0 Arm B: Presence of Chromosomal fusion
Presence of chromosomal fusion with the cutoff CT value of 35 in niraparib treated glioma tissue with IDH and ATRX loss.
Measured: Day 4 Intra-operative sample
Phase 0 Expansion Arm A: Progression-free survival in participants with demonstrated PK effects
6 month progression-free survival (PFS6) rate measured from the time of surgery to date of recurrence.
Measured: 6 months
Phase 0 Expansion Arm B: Progression-free survival in participants with demonstrated PD effects
6 month progression-free survival (PFS6) rate measured from the time of surgery to date of recurrence.
Measured: 6 months
Secondary outcomes (7)
Drug-related toxicity
Incidence of drug-related toxicity
Measured: 24 months
Adverse events
Number of adverse events through study completion, assessed up to 24 months.
Measured: 24 months
Deaths
Number and incidence of deaths
Measured: 24 months
Incidence of clinical laboratory abnormalities per CTCAE
Clinical laboratory abnormalities per CTCAE
Measured: Up to 30 days after the last study dose
Overall survival
Median overall survival
Measured: 48 months
Phase 0 Arm A: Pharmacodynamics (PD) of niraparib
Quantification of percentage of PAR positive cells with IHC assay or PAR concentration in tumor homogenates with an HT PARP pharmacodynamic assay II.
Measured: Day 4 Intra-operative Tissue
Phase 0 Arm B: Pharmacokinetics (PK) of niraparib
Total and unbound niraparib concentration in Gd-enhancing and non-enhancing tumor tissue
Measured: Day 4 Intra-operative Tissue
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2021
- Study start29 Oct 2021
- Primary completion19 Mar 2024
- Study completionMar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nader Sanai
- Sponsor type
- University, hospital or other
- Collaborators
- Barrow Neurological Institute, Ivy Brain Tumor Center, University of California, San Francisco, GlaxoSmithKline
- Responsible party
- Sponsor-investigator, Nader Sanai, St. Joseph's Hospital and Medical Center, Phoenix
- Investigators
- Nader Sanai, MD, Principal investigator, Chief Scientific Officer/Director of the Ivy Brain Tumor Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05076513
- Sponsor's protocol ID
- 2021-13
- Status last verified
- Mar 2026
- First submitted
- 13 Sep 2021
- Last updated
- 9 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 0 'Trigger' Trial of Niraparib in Newly-diagnosed Glioblastoma and Recurrent IDH1/2(+) ATRX Mutant Glioma
- ClinicalTrials.gov ID
- NCT05076513
- Acronym / sponsor ID
- 2021-13
- Conditions
- Glioblastoma, Glioblastoma Multiforme, Glioma, GBM, Glioma, Malignant, Glioblastoma Multiforme of Brain
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- Nader SanaiUniversity, hospital or other
- Collaborators
- Barrow Neurological Institute, Ivy Brain Tumor Center, University of California, San Francisco, GlaxoSmithKline
- Study start
- 29 Oct 2021 (actual)
- Primary completion
- 19 Mar 2024 (actual)
- Study completion
- Mar 2027 (estimated)
- First posted
- 13 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, multi-center Phase 0 study with an expansion phase that will enroll up to 24 participants with newly-diagnosed glioblastoma and up to 18 recurrent glioma participants with IDH mutation and ATRX loss. The trial will be composed of a Phase 0 component (subdivided into Arm A and B) and a therapeutic expansion phase. Patients with tumors demonstrating a positive PK Response (in Arm A) or a positive PD Response (in Arm B) of the Phase 0 component of the study will graduate to a therapeutic expansion phase that combines therapeutic dosing of niraparib plus standard-of-care fractionated radiotherapy (in Arm A) or niraparib monotherapy (in Arm B) until progression of disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: Presumed Newly-Diagnosed glioblastoma | Experimental | Drug: Niraparib, Radiation: Radiation therapyParticipants undergoing resection for a presumed newly-diagnosed glioblastoma (WHO grade 4) will be treated with niraparib for 4 days prior to surgical resection. Participants who proceed to the therapeutic expansion phase of this study will receive niraparib in combination with radiation (60 Gy over 6-7 weeks, as per standard of care). Following radiotherapy, eligible study participants may receive niraparib maintenance treatment. |
| Arm B: Recurrent Glioma (Grades II-IV) | Experimental | Drug: NiraparibParticipants undergoing resection of a recurrent WHO Grade II, III, or IV glioma with IDH1 or IDH2 mutation and ATRX loss will be treated with niraparib for 4 days prior to a planned surgical resection. Participants who proceed to the Expansion cohort will receive niraparib in 28d cycles after surgery. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Arm A participants undergoing resection for a suspected newly diagnosed glioblastoma. For Arm B, participants undergoing resection who have had a prior resection of histologically diagnosed WHO grade II-IV glioma with IDH1 or IDH2 mutation and ATRX loss.
- Arm A participants must have measurable disease preoperatively, defined as at least 1 contrast-enhancing lesion, with 2 perpendicular measurements of at least 1 cm.
- Ability to understand and the willingness to sign a written informed consent document (personally or by the legally authorized representative, if applicable).
- Participant has voluntarily agreed to participate by giving written informed consent (personally or via legally authorized representative(s), and assent if applicable). Written informed consent for the protocol must be obtained prior to any screening procedures. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other procedures.
Key exclusion criteria (17 listed)
- Current use of coumarin-derived anticoagulant for treatment, prophylaxis or otherwise, that cannot be discontinued prior to surgery. Therapy with heparin, low molecular weight heparin (LMWH) or fondaparinux is allowed.
- Pregnancy or lactation.
- Known allergic reactions to components of the niraparib tablet, including FD\&C Yellow No. 5..
- Active infection or fever >38.5°C requiring systemic antibiotic, antifungal or antiviral therapy within 4 weeks of Day 1.
- Known to have active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and active and chronic hepatitis as determined by the investigator.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NiraparibAlso: ZejulaIn Phase 0, 300mg administered orally QD for 4 days prior to resection. In the Expansion cohort/Maintenance phase, niraparib will be administered as described below: * For patients weighing <77 kg (<170 lbs) OR with a platelet count <150,000/mcL, the recommended dosage is 200 mg taken orally once daily. * For patients weighing ≥77 kg (≥170 lbs) AND a platelet count ≥150,000/ mcL, the recommended dosage is 300 mg taken orally once daily. | Drug | Arm A: Presumed Newly-Diagnosed glioblastoma, Arm B: Recurrent Glioma (Grades II-IV) |
| Radiation therapyParticipants in Arm A who move onto the Expansion cohort will receive 6-7 weeks of radiation therapy per standard of care. | Radiation | Arm A: Presumed Newly-Diagnosed glioblastoma |
Primary outcome
Phase 0 Arm A: Total and unbound niraparib concentration in enhancing and nonenhancing tissue
Time frame: Day 4 Intra-operative sample
Tumor to plasma partition coefficients of niraparib for total (Kp) and unbound (Kp,uu) drug levels
Phase 0 Arm B: Presence of Chromosomal fusion
Time frame: Day 4 Intra-operative sample
Presence of chromosomal fusion with the cutoff CT value of 35 in niraparib treated glioma tissue with IDH and ATRX loss.
Phase 0 Expansion Arm A: Progression-free survival in participants with demonstrated PK effects
Time frame: 6 months
6 month progression-free survival (PFS6) rate measured from the time of surgery to date of recurrence.
Phase 0 Expansion Arm B: Progression-free survival in participants with demonstrated PD effects
Time frame: 6 months
6 month progression-free survival (PFS6) rate measured from the time of surgery to date of recurrence.
7 secondary outcomes
Drug-related toxicity
Time frame: 24 months
Adverse events
Time frame: 24 months
Deaths
Time frame: 24 months
Incidence of clinical laboratory abnormalities per CTCAE
Time frame: Up to 30 days after the last study dose
Overall survival
Time frame: 48 months
Phase 0 Arm A: Pharmacodynamics (PD) of niraparib
Time frame: Day 4 Intra-operative Tissue
Phase 0 Arm B: Pharmacokinetics (PK) of niraparib
Time frame: Day 4 Intra-operative Tissue
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2026.
- Ivy Brain Tumor Center WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nader Sanai, MD principal investigator
Chief Scientific Officer/Director of the Ivy Brain Tumor Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Niraparib and Radiation therapy in people with Glioblastoma and Glioblastoma Multiforme, run by Nader Sanai at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 9 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 0 Arm A: Total and unbound niraparib concentration in enhancing and nonenhancing tissue (time frame: Day 4 Intra-operative sample). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2026.