PARP Inhibition for Gliomas (PI-4G or π4g)

Inclusion Criteria:

1. Patients must be able to understand and willing to sign the informed consent form.

2. Patients must be ≥ 18 years of age.

3. Patients must have histologically proven high-grade gliomas - GBM, Astrocytoma, orOligodendroglioma (glioma WHO Grade III or IV) that is now recurrent by MRI orsurgical pathology.

4. Patients must have measurable or evaluable lesions by RANO.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

6. Patient has archival tumor tissue available; or a fresh biopsy of recurrent orpersistent tumor must be obtained for molecular assay by myChoice test (MyriadGenetics) prior to study treatment initiation. Patient will be requested to sharereports from any prior genetic testing with the study investigators.

7. Participants have systolic BP< 140 mmHg or diastolic BP <90 mmHg that has beenadequately treated or controlled.

8. Have adequate organ function defined per protocol.

9. Be able to take oral medications

10. Life expectancy ≥ 3 months, allowing adequate follow up of toxicity evaluation andantitumor activity.

11. Female patient, if of childbearing potential, has a negative serum pregnancy testwithin 72 hours of taking study medication and agrees to abstain from activitiesthat could result in pregnancy from enrollment through 180 days after the last doseof study treatment or is of nonchildbearing potential.

12. Male participant agrees to use an adequate method of contraception starting with thefirst dose of study treatment through 180 days after the last dose of studytreatment. Note: Abstinence is acceptable if this is the established and preferredcontraception for the patient. In addition, men must not donate sperm duringniraparib therapy and for 90 days after receiving the last dose of niraparib.

13. Patient must agree to not breastfeed during the study or for 30 days after the lastdose of study treatment.

14. Participant must agree to not donate blood during the study or for 90 days after thelast dose of study treatment.

15. Participant receiving corticosteroids may continue as long as their dose is stablefor at least 4 weeks prior to initiating protocol therapy.

Exclusion Criteria:

1. Patient has a known additional malignancy that progressed or required activetreatment within the last 3 years (exceptions include basal cell carcinoma of theskin, squamous cell carcinoma of the skin that has undergone potentially curativetherapy, or in situ cervical cancer).

2. Prior treatment with a known poly (ADP-ribose) polymerase (PARP) inhibitor

3. Participants with human immunodeficiency virus (HIV) with detectable viral load.Participants with HIV on effective anti-retroviral therapy with documentedundetectable viral load and CD4 count ≥ 350 within 6 months of the first dose ofstudy treatment are eligible for this trial.

4. Known active hepatitis B or hepatitis C.

5. Known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).

6. Participant is pregnant or expecting to conceive while receiving study treatmentand/or for up to 180 days after the last dose of study treatment. Patient currentlyparticipating and receiving study therapy or has participated in a study of aninvestigational agent and received study therapy or used an investigational devicewithin 4 weeks, or within a time interval less than at least 5 half-lives of theinvestigational agent, whichever is longer, prior to the first dose of study drug.

7. Received prior anticancer therapy (chemotherapy, targeted therapies, radiotherapy,or immunotherapy) within 4 weeks

8. Patients must not have a known hypersensitivity to the components of niraparib orthe excipients (lactose monohydrate and magnesium stearate).

9. Patients must not have had major surgery within 4 weeks (including craniotomy) ofstarting the study and patient must have recovered from any effects of any majorsurgery. Stereotactic biopsy by burr hole is considered a minor surgery, and thosepatients undergoing this surgery will be eligible for the study 2 weekspost-procedure.

10. Patients must not have had radiotherapy encompassing > 20% of the bone marrow within 2 weeks; or any radiation therapy within 1 week prior to Day 1 of protocol therapy.

11. Patients must not have received a transfusion (platelets or red blood cells), colonystimulating factors (eg, granulocyte colony-stimulating factor, granulocytemacrophage colony stimulating factor, or recombinant erythropoietin) ≤ 4 weeks ofthe first dose of study treatment.

12. Patient has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia dueto prior chemotherapy that persisted > 4 weeks and was related to the most recenttreatment.

13. Participants have any clinically significant gastrointestinal abnormalities that mayalter absorption such as malabsorption syndrome or major resection of the stomachand/or bowels.

14. Participants have received live vaccine within 30 days of planned start of studyrandomization.

15. Patients have medical risk due to 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 cordcompression, superior vena cava syndrome, or any psychiatric disorder that prohibitsobtaining informed consent

16. Any medical condition not yet specified above that is considered to possibly,probably or definitely interfere with study procedures, including adequate follow-upand compliance and/or would jeopardize safe treatment.