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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
42
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.
Participants in Arm A who move onto the Expansion cohort will receive 6-7 weeks of radiation therapy per standard of care.
St. Joseph's Hospital and Medical Center
Phoenix, Arizona, United States
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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 6 months
Drug-related toxicity
Incidence of drug-related toxicity
Time frame: 24 months
Adverse events
Number of adverse events through study completion, assessed up to 24 months.
Time frame: 24 months
Deaths
Number and incidence of deaths
Time frame: 24 months
Incidence of clinical laboratory abnormalities per CTCAE
Clinical laboratory abnormalities per CTCAE
Time frame: Up to 30 days after the last study dose
Overall survival
Median overall survival
Time frame: 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.
Time frame: 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
Time frame: Day 4 Intra-operative Tissue
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