Abiraterone, Radiotherapy and Short-Term Androgen Deprivation in Unfavorable Localized Prostate Cancer

Inclusion Criteria:

• One of the following high risk criteria:
• Gleason Score 7 with PSA ≤ 20 ng/ml and clinical T1-2, or
• Gleason Score 8-10, PSA ≤ 20 ng/ml and clinical T1-2a, or
• PSA 10.1-40 ng/ml with GS < 7 and clinical T1-2, or
• Clinical T3 with Gleason Score < 7 and PSA ≤ 10 ng/ml.
• ECOG Performance Status ≤ 1
• CBC with differential with adequate bone marrow function defined as follows:
• Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3, Platelets > 100,000/µL and Hemoglobin > 9g/dL
• Serum potassium ≥ 3.5 mEq/L
• Serum albumin > 3.0 g/dl
• Total bilirubin < 1.5 X of institutional upper limit of normal (ULN)
• AST(SGOT)/ALT(SGPT) < 1.5 X ULN
• Calculated creatinine clearance > 60 mL/min
• Age > 18 years
• Able to swallow a whole tablet and take abiraterone acetate on an empty stomach (defined as no food for two hours before and one hour after abiraterone acetate ingestion)
• Ability to understand and sign a written informed consent document
• Written authorization for use and release of health and research study information has been obtained
• Be willing/able to adhere to the prohibitions and restrictions specified in this protocol
• Subjects who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protections as determined acceptable by the principal investigator during the study and for 1 week after the last dose of abiraterone acetate.

Exclusion Criteria:

• Bone, visceral or soft tissue metastasis, including lymph nodes
• Prior therapy for prostate cancer
• Known serum testosterone < 150 ng/dl or symptoms of hypogonadism (fatigue, hot flashes, hair loss, loss of muscle mass, osteoporosis, low libido, depression) prior to ADT initiation not explained by other medical co-morbidity OR history of testosterone supplement. If questionable, serum testosterone level greater than 150 ng/dl can be used to exclude hypogonadism.
• Previous malignancy within 3 years other than non-melanomatous skin cancer and non-muscle invasive bladder cancer
• Previous pelvic radiotherapy that would prevent prostate/SV irradiation
• Uncontrolled hypertension
• History of gastrointestinal disorders that may interfere with the absorption of study drug (including gastric bypass surgery)
• Concurrent spironolactone use
• Significant concurrent medical condition that would make prednisone/prednisolone use contraindicated
• Receiving any investigational agents currently or within 30 days prior to study screening
• Prior demonstrated hypersensitivity, intolerance or allergy to abiraterone acetate, prednisone or their excipients

• Active co-morbidity, defined as follows:

  • Chronic liver disease with cirrhosis (Child-Pugh B or C) or active hepatitis B or C
  • History of pituitary or adrenal dysfunction
  • Poorly controlled diabetes mellitus (A1c >9% or history of complications including peripheral neuropathy, end organ damage, hospitalization, amputation)
  • Poorly controlled glaucoma
  • Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class III-IV heart disease or known cardiac ejection fraction measurement of < 50% at baseline.
  • Clinical evidence of active infection of any type, including active or symptomatic viral hepatitis.
  • Known immune deficiency and/or HIV-positive patients
  • Any medical condition that warrants long-term corticosteroid use in excess of study dose
• Patients taking strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital)
• Any condition that in the opinion of the Principal Investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing the study requirements