Niraparib In Recurrent IDH 1/2 Gliomas

NCT05406700 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: 21-762
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Low-grade Glioma; IDH2 Gene Mutation; Recurrent Glioma; IDH1 Mutation; Glioma, Malignant

Keywords

Low-grade Glioma; IDH2 Gene Mutation; Recurrent Glioma; IDH1 Mutation; Glioma, Malignant

Outcome Measures

Primary Outcomes (1)

• 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.

  1 year

Secondary Outcomes (9)

• PARP activity in resected tumors

  1 year

• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0"

  Up to one month after discontinuation of treatment

• Median Progression-Free Survival

  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

  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

  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

Study Arms (2)

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

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.

Drug: Resection/Treatment with Niraparib

Interventions

Niraparib DRUG

Oral, daily, dosage per protocol,4 Weeks

Also known as: Zejula

Arm A Treatment with Niraparib

Resection/Treatment with Niraparib DRUG

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.

Also known as: Zejula

Arm A Treatment with Niraparib; Arm B No Treatment with Niraparib

Eligibility Criteria

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

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: collaborator
• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Glioma

Interventions

niraparib; Therapeutics

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Isabel Arrillaga-Romany, MD, Phd

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 25, 2022
• First Posted: June 6, 2022
• Study Start: May 18, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: February 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (1)