A Multi-Center Trial of Androgen Suppression With Abiraterone Acetate, Leuprolide, PARP Inhibition and Stereotactic Body Radiotherapy in Prostate Cancer

Prior treatment

• Any prior treatment for prostate cancer (incudes history of TURP within 5 years of enrollment, chemotherapy, radiation therapy, or anti-androgen therapy)
• 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: non-steroidal anti-androgens (e.g., bicalutamide, flutamide, nilutamide), steroidal antiandrogens (megestrol acetate, cyproterone acetate), oral ketoconazole, chemotherapy, immunotherapy, estrogens, radiopharmaceuticals.
• 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
• Major surgery within 1 month of registration

Other illness

• Clinical or radiographic evidence of distant metastatic disease by CT/bone scan
• Clinical or radiographic evidence of high probability of clinical T4 disease
• History of or active Crohn's disease or ulcerative colitis
• Any gastrointestinal disorder affecting absorption
• Patients with significant cardiovascular disease 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 mmgHg or diastolic blood pressure \>100 mmHg despite anti-hypertensive agents.
• 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

Lab values

• Uncontrolled diabetes or known HbA1c\>10
• Prolonged QTc \>450 ms or any ECG changes that interfere with QT interval interpretation

Other

• 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
• Contraindication to or inability to tolerate MRIs
• Patients with severe depression
• Active pituitary or adrenal dysfunction

• Pathologic biopsy proven adenocarcinoma of the prostate
• At least one of the following 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
• ECOG \< 1
• Adequate organ and marrow function as defined per protocol.
• 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