Reirradiation and Niraparib in Patients With Recurrent Glioblastoma

Inclusion Criteria: * Local recurrence of GBM which can be resected or which is not amenable for surgical resection. Patients who have had surgery may also be included if there is residual enhancing disease on the immediate post-operative MRI or if enhancing disease develops on subsequent follow-up imaging * Recurrent tumour visible on MRI-T1-Gd with the diameter measuring ≤6cm * Prior history of standard dose, conventionally fractionated CNS radiotherapy (i.e. 54-60Gy in 28-33 fractions) * At least 6 months since the end of pre-irradiation * \< 2 prior lines of chemotherapy * Karnofsky Performance Score (KPS) ≥ 70% * Age ≥ 18 years * Written informed consent * Adequate organ and marrow function as defined below: * absolute neutrophil count ≥ 1.5x109/L * platelets ≥ 100 x109/L * haemoglobin \> 9.0 g/dL * total bilirubin ≤ 1.5 x upper limit of normal (ULN) (≤2.0 in patients with known Gilbert's syndrome) OR direct bilirubin ≤ 1 x ULN * Aspartate or alanine transferase (AST or ALT) ≤2.5 x ULN * Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault equation * Negative serum or urine pregnancy test for women of childbearing potential (WOCBP) * Willing to comply with the contraceptive requirements of the trial (see section 6.3 of protocol for details) * Patients receiving corticosteroids may continue to receive them as long as their dose is stable (i.e. not increased by \>2mg) for at least 1-2 weeks prior to initiating protocol therapy * Agree to not donate blood during trial treatment or for 90 days after the last dose of niraparib * Normal blood pressure or adequately treated and controlled hypertension Exclusion Criteria: * Concurrent participation in another interventional clinical trial * Tumour progression or recurrence within 3 months of initial concurrent chemoradiation * Heart failure (compensate or decompensate) * Previous treatment with PARP inhibitors * Previous treatment with re-RT * Women who are pregnant or breast feeding or plan to breastfeed during trial treatment or for 30 days after the last dose of niraparib * Major surgical procedure within 3 weeks prior to the first dose niraparib. Note: Patient must have recovered from any surgical effects before the first dose of niraparib * Received any investigational therapy within 4 weeks prior to, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, the first dose of niraparib * Known hypersensitivity to niraparib components or excipients * Received a transfusion (platelets or red blood cells) within 4 weeks prior to the first dose of niraparib * Received colony stimulating factors (e.g., granulocyte colony-stimulating factor, granulocyte macrophage colony stimulating factor, or recombinant erythropoietin) within 4 weeks prior to the first dose of niraparib * Known history of Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted \> 4 weeks and was related to the most recent treatment * Known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) * Known history of 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 of registration) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent * Prior malignancy (known diagnosis, detection, or treatment of another type of cancer) within 2 years prior to the first dose of niraparib (except basal or squamous cell carcinoma of the skin and cervical cancer that has been definitively treated) * Known leptomeningeal disease, multifocal GBM, or radiologic signs of CNS hemorrhage * Known active hepatitis B (e.g., hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[qualitative\] is detected) infections * Live vaccines within 30 days prior to the first dose of niraparib while participating in this clinical study * If being considered for 300mg dose only: * patient weight \<77Kg * platelet count of \<150 x 109/L * Patient is immunocompromised. Patients with splenectomy are not excluded. Patients with known human immunodeficiency virus (HIV) are not excluded if they meet the following criteria: * Cluster of differentiation 4 (CD4) ≥350/μL and viral load \<400 copies/mL * No history of acquired immunodeficiency syndrome-defining opportunistic infections within 12 months prior to enrolment. * No history of HIV-associated malignancy for the past 5 years. * Concurrent antiretroviral therapy as per the most current National Institutes of Health (NIH) Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV \[NIH, 2021\] started \<4 weeks prior to study enrolment.