Abiraterone Acetate, Prednisone, Leuprolide, Niraparib, and Stereotactic Body Radiotherapy for the Treatment of High Risk or Node Positive Prostate Cancer, The ASCLEPIuS Trial

Inclusion Criteria

• Pathologic biopsy proven adenocarcinoma of the prostate
• Need >= 1 criteria: * cN1 on conventional or PET imaging * Grade group 5 * Grade group 4 * Grade group 3 and PSA >= 20 ng/mL * High probability of radiographic T3 on MRI AND grade group >= 2 * Grade group 3 AND PSA >= 10 ng/mL AND >= 50% positive biopsy cores
• Age >= 18
• Eastern Cooperative Oncology Group (ECOG) =< 1
• Total bilirubin =< 1.5 times the upper institutional limit of normal [ULN] OR direct bilirubin =< 1 x ULN * Note: In subjects with Gilbert’s syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is =< 1.5 x ULN, subject may be eligible
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) and serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2.5 x ULN
• Creatinine =< 1.5 x ULN
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000 / mcL
• Albumin >= 3.0 g/dL
• Potassium >= 3.5 mmol/L
• Use of highly effective contraception (e.g. condoms) for the duration of treatment and a minimum of 120 days thereafter. Men must also agree not to donate sperm for the duration of the study participation, and for at least 120 days thereafter
• International Prostate Symptoms Score (IPSS) =< 20
• Medically fit for treatment and agreeable to follow-up
• Ability to understand and the willingness to sign a written informed consent
• Tissue available for MiOncoSeq testing to assign DNA repair deficiency status

Exclusion Criteria

• Clinical or radiographic evidence of distant metastatic disease by CT/bone scan
• Clinical or radiographic evidence of high probability of clinical T4 disease
• Prostate gland size > 80 cc measured by ultrasound or MRI
• Prominent median lobe assessed by treating physician
• Lack of tissue from biopsy to be sent for correlative studies
• Prior treatment for prostate cancer (includes history of transurethral resection of prostate [TURP] within 5 years of enrollment, chemotherapy, radiation therapy, or anti-androgen therapy). Note: luteinizing hormone-releasing hormone (LHRH) agonist or antagonist therapy alone for <= 3 months is allowed.
• Prohibited within 30 days prior to administration to study treatment: spironolactone and other investigational drug therapies.
• Prohibited 3 months before participant registration and during administration of study treatment: oral ketoconazole, chemotherapy, immunotherapy, estrogens, radiopharmaceuticals
• Anti-androgen therapy administered within the past 30 days, including non-steroidal anti-androgens (e.g., bicalutamide, flutamide, nilutamide) and steroidal antiandrogens (megestrol acetate, cyproterone acetate)
• History of prior pelvic radiation therapy
• Concurrent treatment with strong CYP3A4 inducers such as phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital
• Enrollment concurrently in another investigational drug study within 1 month of registration
• History of another active malignancy within the previous 3 years except for adequately treated skin cancer or superficial bladder cancer
• History of or active Crohn’s disease or ulcerative colitis
• Contraindication to or inability to tolerate MRIs
• Patients with severe depression
• Uncontrolled diabetes or known glycosylated hemoglobin A1C (HbA1c) >= 10
• Any gastrointestinal disorder affecting absorption
• Active pituitary or adrenal dysfunction
• Patients with significant cardiovascular disease within 6 months potentially including severe / unstable angina, recent history of myocardial infarction, clinically significant heart failure, cerebrovascular disease, venous thromboembolic events, clinically significant arrhythmias)
• Uncontrolled hypertension with persistently elevated systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg despite anti-hypertensive agents
• Prolonged corrected QT (QTc) > 450 ms or any electrocardiogram (ECG) changes that interfere with QT interval interpretation
• Major surgery within 1 month of registration
• History of myelodysplastic syndrome or leukemia
• A known hypersensitivity to niraparib, abiraterone acetate, leuprolide, and/or prednisone
• Active infection or other medical condition that would be a contraindication to prednisone use
• Patients with known active hepatitis or chronic liver disease including cirrhosis
• Any condition that in the opinion of the investigator would preclude participation in this study