Trial of Niraparib in Participants With Newly-diagnosed Glioblastoma and Recurrent Glioma

NCT05076513 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: 2021-13
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief 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. 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

Glioma; GBM; Glioma, Malignant; Glioblastoma Multiforme of Brain; Glioblastoma; Glioblastoma Multiforme

Outcome Measures

Primary Outcomes (4)

• 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

  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.

  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.

  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.

  6 months

Secondary Outcomes (7)

• Drug-related toxicity

  24 months

• Adverse events

  24 months

• Deaths

  24 months

• Incidence of clinical laboratory abnormalities per CTCAE

  Up to 30 days after the last study dose

• Overall survival

  48 months

Study Arms (2)

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.

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.

Drug: Niraparib

Interventions

Niraparib DRUG

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.

Also known as: Zejula

Arm A: Presumed Newly-Diagnosed glioblastoma; Arm B: Recurrent Glioma (Grades II-IV)

Radiation therapy RADIATION

Participants in Arm A who move onto the Expansion cohort will receive 6-7 weeks of radiation therapy per standard of care.

Arm A: Presumed Newly-Diagnosed glioblastoma

Eligibility Criteria

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

You may qualify if:

• 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
• 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).

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Nader Sanai: lead
• Barrow Neurological Institute: collaborator
• Ivy Brain Tumor Center: collaborator
• University of California, San Francisco: collaborator
• GlaxoSmithKline: collaborator

Study Sites (1)

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

Location

Related Links

• Ivy Brain Tumor Center Website

MeSH Terms

Conditions

Glioblastoma; Glioma

Interventions

niraparib; Radiotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Nader Sanai, MD

  Chief Scientific Officer/Director of the Ivy Brain Tumor Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Scientific Officer/Director

Study Record Dates

• First Submitted: September 13, 2021
• First Posted: October 13, 2021
• Study Start: October 29, 2021
• Primary Completion: March 19, 2024
• Study Completion (Estimated): March 1, 2027
• Last Updated: March 9, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)