Title A Multicenter, Open-label, Single-arm, Phase 2 Study of Abiraterone Acetate Plus Prednisone in Subjects with Advanced Prostate Cancer Without Radiographic Evidence of Metastatic Disease


CC CC00097

Hospital Main Campus

Stage N/A

Phase Phase 2

Disease Prostate

Drug Abiraterone Acetate, Prednisone



  1. Primary Objective
    • To demonstrate that abiraterone acetate plus prednisone effectively decreases PSA in subjects with non-metastatic CRPC who have a rising PSA despite castrate levels of testosterone.
  2. Secondary Objectives
    • To describe the time to radiographic progression of disease in subjects treated with abiraterone acetate in addition to the current standard of care.
    • To describe the safety profile of abiraterone acetate when taken with prednisone 5 mg daily.
Inclusion Criteria

Inclusion Criteria

  1. Be a male ≥18 years of age
  2. Have adenocarcinoma of the prostate with histological or cytological confirmation without neuroendocrine differentiation or small cell histology
  3. Criterion modified per amendment 3a. Subjects must currently be receiving and have been receiving continuous treatment with GnRH monotherapy for at least 6 months before screening with a serum testosterone level of < 50 ng/dL (< 2.0 nM) or have undergone an orchiectomy with a serum testosterone level of < 50 ng/dL (< 2.0 nM)
  4. Have rising PSA defined as a PSA of ≥ 10 ng/mL obtained at screening or PSADT of ≤ 10 months with the first of the 3 consecutive PSA values used to calculate PSADT ≥ 2.0 ng/mL.
  5. Criterion modified per amendment 5a. Have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  6. Have a baseline serum potassium of ≥ 3.5 mEq/L
  7. Have a hemoglobin of ≥ 9.0 g/dL
  8. Have an absolute neutrophil count of > 1500 cell/mm³
  9. Have a platelet count of ≥ 100,000/µL
  10. Have normal PT/PTT (INR). For patients not receiving anticoagulants, this means the patient is normal according to the lab values. In the case of patients receiving anticoagulants, the investigator will determine the appropriate therapeutic target for that patient and whether the INR obtained at screening is acceptable.
  11. Have a serum albumin of ≥ 3.0 g/dL
  12. Have a calculated creatinine clearance ≥ 60 mL/min
  13. Have aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin levels < 1.5 x ULN
  14. Be capable of swallowing study agents whole as a tablet
  15. Be willing/able to adhere to the prohibitions and restrictions specified in this protocol
  16. Have signed an informed consent document indicating that the subject understands the purpose of and procedures required for the study and are willing to participate in the study.
Exclusion Criteria

Exclusion Criteria

  1. Have prior or current evidence of local disease progression or metastatic disease as defined by modified RECIST criteria
  2. Have received chemotherapy for treatment of CRPC; however, if a patient received chemotherapy in an adjuvant setting, prior to having CRPC, for castrate-sensitive prostate cancer, the patient is still eligible.
  3. Criterion modified per amendment. Are currently receiving any antiandrogen therapy (e.g., bicalutamide, flutamide, or nilutamide).
    • For subjects previously treated with antiandrogen therapy, there must be documentation of at least 2 consecutive rising PSA values, obtained at least 2 weeks apart obtained prior to screening.
    • For subjects previously treated with flutamide, at least 1 of the PSA values must be obtained 4 weeks or more after flutamide discontinuation.
    • For subjects previously treated with bicalutamide or nilutamide, at least 1 of the PSA values must be obtained 6 weeks or more after antiandrogen discontinuation.
  4. Have an active infection or other medical condition that would contraindicate prednisone use
  5. Have uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 95 mmHg); subjects with a history of hypertension are permitted in the study provided their blood pressure is controlled by anti-hypertensive therapy
  6. Have active hepatitis or chronic liver disease
  7. Have a history of pituitary or adrenal dysfunction
  8. Have clinically significant heart disease as evidenced by myocardial infarction or arterial thrombotic events in the past 6 months, severe or unstable angina, New York Heart Association Class III or IV heart disease, or left ventricular ejection fraction of ≤ 50% at baseline
  9. Have poorly controlled diabetes
  10. Have a history of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agents
  11. Have received an investigational therapeutic within 30 days of screening
  12. Have a pre-existing condition that warrants long-term corticosteroid use in doses in excess of prednisone 5 mg once daily
  13. Have known allergies, hypersensitivity, or intolerance to abiraterone acetate or prednisone or their excipients (refer to the Pharmacy Reference Manual for further description of the study agents)
  14. Be taking or require the use of prohibited medications as listed in Section 8.2.2
  15. Have any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements
  16. Have partners of childbearing potential and are not willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator and sponsor during the study and for 1 week after last abiraterone acetate administration
  17. Individuals with a history of non-prostate malignancy are ineligible for this study with the following exceptions. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 3 years: basal cell or squamous cell carcinoma of the skin.
  18. Have previously received agents having any CYP17 inhibitory activity for the treatment of prostate cancer, such as ketoconazole.
  19. Have previously received aminoglutethimide.