Clinical Research Trials

Key Trial Criteria

• Key Inclusion Criteria

  For a patient to be eligible for participation in this study, all of the following criteria must apply.

  • Male, age ≥ 18 years
  • Karnofsky performance status ≥ 70 (Appendix 1)
  • Life expectancy of ≥ 12 months as determined by treating investigator
  • Written Authorization for Use and Release of Health and Research Study Information (HIPAA authorization per institutional requirements)
  • Willing/able to adhere to the prohibitions and restrictions specified in this protocol
  • Willing to take abiraterone acetate on an empty stomach and should be able to swallow tablets whole, without crushing/chewing tablets. Must have the ability to swallow, retain, and absorb oral medication.
  • Medications known to lower the seizure threshold (see list under prohibited meds, appendix 2) must be discontinued or substituted at least 4 weeks prior to study entry.
  • Agrees to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug. Must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug. Abstinence is an acceptable method of birth control.
  • Adequate bone marrow function as shown by ANC ≥ 1.0 x 109/L, Platelets ≥ 100 x 109/L, Hb≥9 g/dL, (independent of transfusion and/or growth factors within 3 months prior to Cycle 1 Day 1)
  • Serum potassium ≥ 3.5 mEq/L
  • Serum albumin of ≥ 3.0 g/dl
  • AST/SGOT and ALT/SGPT <2.5 x Institutional Upper Limit of Normal (ULN)
  • Serum total bilirubin ≤ 1.5 x Institutional ULN (Note: In subjects with Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5 × ULN, subject may be eligible)
  • GFR ≥45 mL/min
  • Histologically confirmed diagnosis of adenocarcinoma of the prostate. Histologic variants of prostate cancer comprising of >50% of the tumor including neuroendocrine features and small cell carcinoma of the prostate are excluded.
  • Radiographic evidence of metastatic disease based on RECIST 1.1 Criteria OR by prostate cancer-specific PET imaging. Evaluable non-target lesions and/or bone only metastasis are permitted per RECIST 1.1 and PCWG3 guidelines. Non-target, pathological lymph nodes ≥ 10 mm and less than 15 mm in the short axis are permitted.
  • Ongoing ADT using an LHRH agonist (e.g. leuprolide, goserelin) or antagonist (e.g. degarelix) must continue on therapy unless prior bilateral orchiectomy has been performed.
  • PSA ≥ 2.0 ng/mL
  • Evidence of castration-resistant disease in the setting of ongoing ADT (medical or surgical) as evidenced by one of the following:
    • Absolute rise in PSA of 2.0 ng/mL or an increase >25% from the nadir, minimum 2 consecutive rising PSA levels with an interval of ≥ 1 week between each PSA level, OR
    • CT or MRI based evidence of disease progression (soft tissue, nodal or visceral disease progression) according to PCWG3 criteria or RECIST 1.1 criteria, OR
    • At least 1 new bone scan lesion as compared to the most immediate prior radiologic studies.
  • A minimum of 2 weeks elapsed off of antiandrogen therapy prior to start of study drug (i.e. flutamide, nilutamide, bicalutamide).
  • A minimum of 2 weeks elapsed off of sipuleucel-T and radiation therapy prior to start of study drug.
  • A minimum of 4 weeks from any major surgery prior to start of study drug.
  • Self-reported race of either African American or Caucasian.
  • Ability to understand and the willingness to sign a written informed consent document. If the subject is unable to understand the consent due to comorbidity, such as Alzheimer's disease, consent by a legally authorized representative and assent by the subject will be obtained.

• Key Exclusion Criteria

  A patient will not be eligible for participation in this study if any of the following criteria apply.

  • Prior treatment with abiraterone acetate, enzalutamide, apalutamide (ARN-509), galaterone (TOK-001), orteronel (TAK-700), or similar agent.
  • Active infection or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated.
  • Active or symptomatic infection including HIV, viral hepatitis or chronic liver disease.
  • Any chronic medical condition requiring a higher dose of corticosteroid than 5mg prednisone/prednisolone bid.
  • Have known allergies, hypersensitivity, or intolerance to abiraterone acetate, apalutamide or prednisone or their excipients.
  • Pathological finding consistent with small cell carcinoma of the prostate.
  • Symptomatic liver or visceral organ metastasis.
  • Have a history of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agents.
  • Known brain metastasis.
  • Prior cytotoxic chemotherapy or biologic therapy for the treatment of CRPC. Note: sipuleucel-T is permitted with a 2-week washout.
  • Previously treated with ketoconazole for prostate cancer for greater than 7 days.
  • Prior systemic treatment with an azole anti-fungal drug (e.g. fluconazole, itraconazole) within 4 weeks of Cycle 1, Day 1.
  • Uncontrolled hypertension (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg). Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment.
  • Poorly controlled diabetes, FBS ≥200 mg/dL.
  • History of pituitary or adrenal dysfunction.
  • Symptomatic Atrial Fibrillation, or other symptomatic cardiac arrhythmia.
  • Other malignancy, except non-melanoma skin cancer, with a ≥ 30% probability of recurrence within 24 months.
  • History of any of the following:
    • Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 6 months of Cycle 1 Day 1, brain arteriovenous malformation, Schwannoma, meningioma, or other benign 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 (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to first dose of study drug. Venous thrombolic events within 6 months are permitted IF they are not attributed to prostate cancer (in the opinion of the treating physician).
  • Avoid concomitant strong CYP3A4 inducers during abiraterone acetate treatment.
  • Avoid co-administration of abiraterone acetate with CYP2D6 substrates that have a narrow therapeutic index. If an alternative treatment cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate.
  • Baseline moderate or severe hepatic impairment (Child Pugh Class B & C).
  • Use of herbal products that may decrease PSA levels (i.e., saw palmetto) refer to section 8.3.2 (no washout period required).
  • Administration of an investigational therapeutic within 30 days prior to Cycle 1, Day 1.
  • Any condition which, in the opinion of the investigator, would preclude participation in this trial.