Antiandrogen Therapy and SBRT in Treating Patients With Recurrent, Metastatic Prostate Cancer

Open to males ages 18 years and up

• Confirmed diagnosis of prostate adenocarcinoma after radical prostatectomy (primary small cell carcinoma of the prostate is not allowed, however adenocarcinoma with neuroendocrine differentiation is allowed)
• Presence of 1-5 visible metastases (by PSMA PET-CT)
  • At least one metastasis must be M1a-b
  • Visceral metastases are not allowed
  • Patients may have any number of pelvic nodal metastases (but largest must be < 2 cm)
  • Metastases must be amenable to treatment with SBRT
  • Biopsy of one metastasis must be attempted, unless unsafe to perform
• Patient must be fit to undergo SBRT to all visible sites of metastases, ADT
• Total testosterone > 150 ng/dL prior to ADT (optimal time to measure total testosterone is between 8 and 9 am)
• Adequate performance status (Eastern Cooperative Oncology Group [ECOG] 0-1)
• Hemoglobin >= 9.0 g/dL, independent of transfusion and/or growth factors within 3 months prior to randomization
• Platelet count >= 100,000 x 10⁹/uL independent of transfusion and/or growth factors within 3 months prior to randomization
• Serum albumin >= 3.0 g/dL
• Glomerular filtration rate (GFR) >= 45 mL/min
• Serum potassium >= 3.5 mmol/L
• Serum total bilirubin =< 1.5 x upper limits of normal (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
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x ULN
• Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry

• Any evidence of spinal cord compression (radiological or clinical)
• Prior pelvic malignancy
• Prior pelvic radiation aside from salvage prostate radiation
• Concurrent malignancy aside from superficial skin cancers or superficial bladder tumors
• Inability to undergo radiotherapy, or ADT
• Primary small cell carcinoma of the prostate (prostate adenocarcinoma with neuroendocrine differentiation is allowed)
• Inflammatory bowel disease or active collagen vascular disease
• History of any of the following:
  • Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system [CNS] or meningeal disease which may require treatment with surgery or radiation therapy)
  • Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (eg, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to randomization
• Current evidence of any of the following:
  • Uncontrolled hypertension
  • Gastrointestinal disorder affecting absorption
  • Active infection (eg, human immunodeficiency virus [HIV] or viral hepatitis)
  • Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone/prednisolone once daily
  • Any condition that in the opinion of the investigator would preclude participation in this study

  • Concomitant strong CYP3A4 inducers. (If a strong CYP3A4 inducer must be co-administered, abiraterone acetate dose frequency will be adjusted). [SAFETY: Warning against use with CYP2C8 inhibitors with narrow therapeutic index is also pertinent to be included as it is also part of United States Prescribing

    Information (USPI): In a CYP2C8 drug-drug interaction trial in healthy subjects, the area under curve (AUC) of pioglitazone (CYP2C8 substrate) was increased by 46% when pioglitazone was given together with a single dose of 1,000 mg abiraterone acetate. Therefore, patients should be monitored closely for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used concomitantly with ZYTIGA]

  • Treatment with CYP2D6 substrates that have a narrow therapeutic index. If an alternative treatment cannot be used, a dose reduction of the CYP2D6 substrate may be considered
  • Baseline moderate and severe hepatic impairment (ChildPugh Class B & C)
• Presence of visceral metastases (i.e., stage M1c)