Low-grade GliomaEarly Phase 1NCT05406700
Niraparib In Recurrent IDH 1/2 Gliomas
A Early Phase 1 study testing Niraparib and Resection/Treatment with Niraparib in people with Low-grade Glioma and IDH2 Gene Mutation, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
This is a randomized, two-arm, open-label, phase 0 trial to assess intratumoral pharmacokinetics and pharmacodynamics of niraparib in subjects with progressive IDH1 or IDH2 mutant glioma. This research study involves an experimental treatment called Niraparib. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Low-grade Glioma, IDH2 Gene Mutation, Recurrent Glioma
- What is being tested?
- Niraparib and Resection/Treatment with Niraparib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 18 May 2023to Oct 2026
- 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
- Participants must be ≥18 years of age.
- Participants must have histologically or cytologically confirmed glioma, with documented IDH1 and/or IDH2 gene-mutation at time of initial diagnosis
- Participants must have radiographic evidence of progression/recurrence per RANO criteria for low grade gliomas (LGG) on MRI scan
- Participants must be willing and able to get serial MRI scans
- Participants must have surgically accessible tumors and be surgical candidates.
- Participants must be ≥12 weeks from completion of radiation to the CNS.
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- Participants must have a baseline brain MRI scan within 21 days prior to Day 1 of treatment.
- Participants must be on a stable or decreasing dose of glucocorticoids for 7 days prior to registration.
- Patient must have Karnofsky Performance Score (KPS) ≥ 70
- Patient must have expected survival of ≥ 6 months.
- Participant must have adequate organ function, defined as follows:
- Absolute neutrophil count ≥ 1,500/μL
- Platelets ≥ 100,000/μL
- Hemoglobin ≥ 9 g/dL
- Calculated creatinine clearance ≥ 30 mL/min/1.73 m2 using the Cockcroft- Gault equation
- Total bilirubin ≤ 1.5 x ULN (≤2.0 in patients with known Gilberts syndrome) OR direct bilirubin ≤ 1 x ULN
- Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN unless liver metastases are present, in which case they must be ≤ 5 x ULN
- Patient must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of cancer. (Patients with residual Grade 1 toxicity due to prior chemotherapy or alopecia of any grade are allowed).
- Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
- Female participant has a negative urine or serum pregnancy test within 3 days prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 180 days after the last dose of study treatment, or is of non-childbearing potential. Non-childbearing potential is defined as follows (by other than medical reasons):
- ≥45 years of age and has not had menses for >1 year
- Patients who have been amenorrhoeic for <2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation
- Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use 2 adequate barrier methods throughout the study, starting with the screening visit through 180 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
- Participant must agree to not breastfeed during the study or for 30 days after the last dose of study treatment.
- Male participant agrees to use an adequate method of contraception starting with the first dose of study treatment through 90 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
- Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent
Who cannot join
- Participants must have radiographic evidence of primarily disease progression/recurrence per RANO criteria for low grade gliomas (LGG).
- Participant must not be simultaneously enrolled in any interventional clinical trial
- Participant must not have had major surgery ≤ 4 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects.
- Patients may not have received systemic anticancer therapy <28 days prior to their first day of study drug administration. Participants may not have received lomustine < 6 weeks prior to the first day of study drug.
- Patients who received an investigational agent <28 days prior to their first day of study drug administration.
- Participant must not have received a transfusion (platelets or red blood cells) ≤ 4 weeks prior to initiating protocol therapy. Participant must not have received colony-stimulating factors (e.g., granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 4 weeks prior initiating protocol therapy.
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- Participant has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted > 4 weeks and was related to the most recent treatment.
- Participant must not have a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent
- Participant must not have had diagnosis, detection, or treatment of another type of cancer ≤ 2 years prior to initiating protocol therapy (except basal or squamous cell carcinoma of the skin and cervical cancer that has been definitively treated).
- Participants who are pregnant or breast-feeding.
- Participants with known hypersensitivity to any of the components of niraparib.
- Participants with known infection with human immunodeficiency virus (HIV) or active hepatitis B or C
- Participants with any other medical or psychological condition, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate, or participate in the study.
- Participants with known dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally.
- Participants that have had radiation therapy encompassing >20% of the bone marrow within 2 weeks; or any radiation therapy within 1 week prior to Day 1 of protocol therapy.
- Participant must not have known or symptomatic leptomeningeal metastases.
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02115
About this study
Official title: A Phase 0 Clinical Trial to Evaluate Drug Concentrations and Pharmacodynamic Parameters of Niraparib in Tumor Tissue of Patients With Surgically Accessible Recurrent IDH 1/2 Gliomas
This is a randomized, two-arm, open-label, phase 0 trial to assess intratumoral pharmacokinetics and pharmacodynamics of niraparib in subjects with progressive IDH1 or IDH2 mutant glioma.
- This research study involves an experimental treatment called Niraparib.
Read the detailed description
This is a randomized, two-arm, open-label, phase 0 trial to assess intratumoral pharmacokinetics and pharmacodynamics of niraparib in subjects with progressive IDH1 or IDH2 mutant glioma.
- This research study involves an experimental treatment called Niraparib.
- The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.
- Participants will be randomized into one of two groups
- Arm A: 1 cycle of Niraparib, followed by surgery, followed by up to 12 cycles of niraparib.
- Arm B: Surgery followed by up to 12 cycles of niraparib
Participants will receive study treatment for up to 12 Cycles (1 cycle is 28 days long) and will be followed for up to 5 years after the study treatment.
It is expected that about 16 people will take part in this research study.
This research study is a Pilot Study to investigate the study drug's (niraparib) activity in tumor tissue. The U.S. Food and Drug Administration (FDA) has not approved niraparib for this specific disease but it has been approved for other uses.
- Being tested
- Niraparib, Resection/Treatment with Niraparib
- Keywords
- Low-grade Glioma, IDH2 Gene Mutation, Recurrent Glioma, IDH1 Mutation, Glioma, Malignant
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NiraparibDrug
Also called Zejula
Oral, daily, dosage per protocol,4 Weeks
Resection/Treatment with NiraparibDrug
Also called Zejula
The participants in both arms will resume/start on treatment with niraparib 2 -4 weeks after surgery.
Treatment can be held for an additional 28 days to allow for recovery from surgery, at the investigator's discretion. Participants will continue treatment for up to 12 total cycles of treatment or until tumor progression, unacceptable toxicity or withdrawal of consent.
| Study group | Role | What they receive |
|---|---|---|
| Arm A Treatment with Niraparib | Experimental | Patients randomized to arm A will receive niraparib daily and undergo tumor resection after 28 days (+/- 7 days) of treatment. The participants in both arms will resume/start on treatment with niraparib 2 -4 weeks after surgery . Participants will continue treatment for up to 12 total cycles of treatment or until tumor progression, unacceptable toxicity or withdrawal of consent Receives: Drug: Niraparib; Drug: Resection/Treatment with Niraparib |
| Arm B No Treatment with Niraparib | Active comparator | Subjects in arm B will not receive niraparib prior to surgery. The participants in both arms will resume/start on treatment with niraparib 2 -4 weeks after surgery . Participants will continue treatment for up to 12 total cycles of treatment or until tumor progression, unacceptable toxicity or withdrawal of consent. Receives: Drug: Resection/Treatment with Niraparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Drug concentration of niraparib
Drug concentrations of niraparib in enhancing and non-enhancing tumor tissue from subjects treated with the agent for one month prior to surgery.
Measured: 1 year
Secondary outcomes (9)
PARP activity in resected tumors
PARP activity assessed by measuring levels of poly (ADP)-ribose (PAR)s
Measured: 1 year
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0"
NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Measured: Up to one month after discontinuation of treatment
Median Progression-Free Survival
measured using RANO criteria for low grade glioma
Measured: is defined as the time from randomization (or registration) to the earlier of progression or death due to any cause. Patients alive without disease progression are censored at date of last disease evaluation up to 5 years
Median Overall Survival
calculated with the Kaplan-Meier method and the Log-Rank test will be conducted to compare between the study arms
Measured: Overall Survival (OS) is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive up to 5 years
Duration of Overall Response
ORR will be calculated as the proportion of patients that are determined to be CR, PR or SD
Measured: one month from start of treatment (Arm A only) and 2, 4, 6 and 12 months out from start of treatment after surgery up to 5 years
Response Rate in subjects with recurrent glioma after 1 month of treatment
measured by the Response Assessment in Neuro-Oncology (RANO) Working Group for low-grade gliomas
Measured: 1 month
Response Rate in subjects with residual glioma after surgery
measured by the Response Assessment in Neuro-Oncology (RANO) Working Group for low-grade gliomas (only in patients with subtotal resection)
Measured: Up to 5 years
D-2-hydroxyglutarate (2-HG) levels by MRS
D-2-hydroxyglutarate (2-HG) levels by MRS
Measured: before and one-month post treatment with niraparib up to 3 months
Genomic profile
assessed by whole exome sequencing (WES) performed on resected tumor
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2022
- Study start18 May 2023
- Primary completionJul 2026 (estimated)
- Study completionOct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Low-grade GliomaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Principal investigator, Isabel Arrillaga-Romany, Massachusetts General Hospital
- Investigators
- Isabel Arrillaga-Romany, MD, Phd, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05406700
- Sponsor's protocol ID
- 21-762
- Status last verified
- Jul 2026
- First submitted
- 25 Apr 2022
- Last updated
- 24 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 0 Clinical Trial to Evaluate Drug Concentrations and Pharmacodynamic Parameters of Niraparib in Tumor Tissue of Patients With Surgically Accessible Recurrent IDH 1/2 Gliomas
- ClinicalTrials.gov ID
- NCT05406700
- Acronym / sponsor ID
- 21-762
- Keywords
- Low-grade Glioma, IDH2 Gene Mutation, Recurrent Glioma, IDH1 Mutation, Glioma, Malignant
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- 18 May 2023 (actual)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Oct 2026 (estimated)
- First posted
- 6 Jun 2022 (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 a randomized, two-arm, open-label, phase 0 trial to assess intratumoral pharmacokinetics and pharmacodynamics of niraparib in subjects with progressive IDH1 or IDH2 mutant glioma.
- This research study involves an experimental treatment called Niraparib.
Detailed description
This is a randomized, two-arm, open-label, phase 0 trial to assess intratumoral pharmacokinetics and pharmacodynamics of niraparib in subjects with progressive IDH1 or IDH2 mutant glioma.
- This research study involves an experimental treatment called Niraparib.
- The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.
- Participants will be randomized into one of two groups
- Arm A: 1 cycle of Niraparib, followed by surgery, followed by up to 12 cycles of niraparib.
- Arm B: Surgery followed by up to 12 cycles of niraparib
Participants will receive study treatment for up to 12 Cycles (1 cycle is 28 days long) and will be followed for up to 5 years after the study treatment.
It is expected that about 16 people will take part in this research study.
This research study is a Pilot Study to investigate the study drug's (niraparib) activity in tumor tissue. The U.S. Food and Drug Administration (FDA) has not approved niraparib for this specific disease but it has been approved for other uses.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A Treatment with Niraparib | Experimental | Drug: Niraparib, Drug: Resection/Treatment with NiraparibPatients randomized to arm A will receive niraparib daily and undergo tumor resection after 28 days (+/- 7 days) of treatment. The participants in both arms will resume/start on treatment with niraparib 2 -4 weeks after surgery . Participants will continue treatment for up to 12 total cycles of treatment or until tumor progression, unacceptable toxicity or withdrawal of consent |
| Arm B No Treatment with Niraparib | Active comparator | Drug: Resection/Treatment with NiraparibSubjects in arm B will not receive niraparib prior to surgery. The participants in both arms will resume/start on treatment with niraparib 2 -4 weeks after surgery . Participants will continue treatment for up to 12 total cycles of treatment or until tumor progression, unacceptable toxicity or withdrawal of consent. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Participants must be ≥18 years of age.
- Participants must have histologically or cytologically confirmed glioma, with documented IDH1 and/or IDH2 gene-mutation at time of initial diagnosis
- Participants must have radiographic evidence of progression/recurrence per RANO criteria for low grade gliomas (LGG) on MRI scan
- Participants must be willing and able to get serial MRI scans
- Participants must have surgically accessible tumors and be surgical candidates.
Key exclusion criteria (16 listed)
- Participants must have radiographic evidence of primarily disease progression/recurrence per RANO criteria for low grade gliomas (LGG).
- Participant must not be simultaneously enrolled in any interventional clinical trial
- Participant must not have had major surgery ≤ 4 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects.
- Patients may not have received systemic anticancer therapy <28 days prior to their first day of study drug administration. Participants may not have received lomustine < 6 weeks prior to the first day of study drug.
- Patients who received an investigational agent <28 days prior to their first day of study drug administration.
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: ZejulaOral, daily, dosage per protocol,4 Weeks | Drug | Arm A Treatment with Niraparib |
| Resection/Treatment with NiraparibAlso: ZejulaThe participants in both arms will resume/start on treatment with niraparib 2 -4 weeks after surgery. Treatment can be held for an additional 28 days to allow for recovery from surgery, at the investigator's discretion. Participants will continue treatment for up to 12 total cycles of treatment or until tumor progression, unacceptable toxicity or withdrawal of consent. | Drug | Arm A Treatment with Niraparib, Arm B No Treatment with Niraparib |
Primary outcome
Drug concentration of niraparib
Time frame: 1 year
Drug concentrations of niraparib in enhancing and non-enhancing tumor tissue from subjects treated with the agent for one month prior to surgery.
9 secondary outcomes
PARP activity in resected tumors
Time frame: 1 year
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0"
Time frame: Up to one month after discontinuation of treatment
Median Progression-Free Survival
Time frame: is defined as the time from randomization (or registration) to the earlier of progression or death due to any cause. Patients alive without disease progression are censored at date of last disease evaluation up to 5 years
Median Overall Survival
Time frame: Overall Survival (OS) is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive up to 5 years
Duration of Overall Response
Time frame: one month from start of treatment (Arm A only) and 2, 4, 6 and 12 months out from start of treatment after surgery up to 5 years
Response Rate in subjects with recurrent glioma after 1 month of treatment
Time frame: 1 month
Response Rate in subjects with residual glioma after surgery
Time frame: Up to 5 years
D-2-hydroxyglutarate (2-HG) levels by MRS
Time frame: before and one-month post treatment with niraparib up to 3 months
Genomic profile
Time frame: Up to 5 years
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 24 Jul 2026.
- Individual participant dataSharing planned: Yes. The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
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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.
Isabel Arrillaga-Romany, MD, Phd principal investigator
Massachusetts General Hospital
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 Resection/Treatment with Niraparib in people with Low-grade Glioma and IDH2 Gene Mutation, run by Massachusetts General Hospital 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 26 inclusion and 16 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 24 Jul 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?
Drug concentration of niraparib (time frame: 1 year). 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 24 Jul 2026.