Study of Abiraterone Acetate and Prednisone in Combination With Cabazitaxel in Patients With Prostate Cancer

Inclusion Criteria:

* Written informed consent has been obtained.
* Adults over 18 years of age.
* Histologically or cytologically proven adenocarcinoma of the prostate.
* Stage IV disease as evidenced by soft tissue, visceral and/or bony metastasis must be Response Evaluation Criteria in Solid Tumors (RECIST) evaluable on CT scan and/or bone scan
* Progressive disease while receiving hormonal therapy or after surgical castration documented by at least one of the following:

  1. Increase in measurable disease per RECIST 1.1,
  2. Appearance of new lesions on bone scan consistent with progressive prostate cancer (\>2 new lesions on bone scans if this is the only measure of PD),
  3. rising PSA defined as 2 sequential increases above a previous lowest reference value.

     * Each value must be obtained at least 1 week apart.
* PSA at least 2 ng/mL
* Received prior docetaxel chemotherapy
* Received prior abiraterone acetate, but not within the 3 months prior to study drug dosing.
* Testosterone level \<50 ng/mL. Patients receiving Leutinizing Hormone Releasing Hormone (LHRH) agonists or antagonists must be continued to maintain castrate levels of testosterone while on study.
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
* Adequate hematologic function:

  1. platelet \>100, 000/uL;
  2. neutrophil count of \>1500 cell/mm3;
  3. hemoglobin \>9.0 g/dL)
* Adequate renal function (Creatinine clearance \> 50 mL/min)
* Adequate potassium level (\> 3.5 mEq/dL)
* Adequate hepatic function

  1. bilirubin \< 1.5 X upper limit of normal (ULN),
  2. alanine aminotransferase (ALT) \< 1.5 X ULN,
  3. aspartate aminotransferase (AST) \< 1.5 X ULN.
  4. serum albumin of ≥ 3.0 g/dL.
* Controlled blood pressure, defined as blood pressure ≤ 140/90 on average (3 separate readings taken at screening visit in a relaxed clinical environment and averaged)
* Must be able to take oral medication without crushing, dissolving or chewing tablets
* Willing to take abiraterone acetate on empty stomach;

  (1) no food should be consumed at least two hours before and for at least one hour after the dose of abiraterone acetate is taken.
* Patients must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
* Written authorization for use and release of health and research study information has been obtained.
* Patients who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protection during the study and for 1 week after the last dose of abiraterone acetate.

Exclusion Criteria:

* Surgery or radiation therapy within 2 weeks, or
* Cytotoxic anti-cancer therapy within 3 weeks, or
* Non-cytotoxic anti-cancer therapy within 2 weeks, or 5 half-lives (whichever is shorter) of Study Day 1.
* Prior radiotherapy to ≥ 40% of bone marrow.
* Prior treatment with Radium 223.
* Use of an investigational therapeutic agent within 30 days.
* Have a history of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agents.
* Prior treatment with cabazitaxel.
* Known chronic infection with human immunodeficiency virus (HIV).
* Known active, or symptomatic, brain metastasis.
* Blood pressure \>140/90 on average (3 separate readings taken at screening visit in a relaxed clinical environment and averaged).
* History of autoimmune disorder requiring daily corticosteroid therapy of greater than prednisone 10mg daily, or its equivalent.
* Baseline peripheral edema \> grade 3.
* Pre-existing diarrhea uncontrolled with supportive care;
* Prior hemorrhagic diarrhea due to ulcerative colitis, inflammatory bowel disease or other cause;
* Active, uncontrolled peptic ulcer disease even in the setting of proton-pump inhibitor or Histamine2-blocker use.
* Pre-existing peripheral neuropathy grade \> 2.
* Documented hypersensitivity (CTCAE grade \> 2) to any drug containing polysorbate 80.
* Have known allergies or hypersensitivity to abiraterone acetate or prednisone or their excipients.
* Contraindications to steroid use.
* Need for medications that strongly induce or inhibit cytochrome P450 3A4 (CYP3A4) or cytochrome P450 2D6 (CYP2D6) activity. (see section 7.2.3 for details)
* Serious infection requiring parenteral antibiotics within 14 days of enrollment.
* Poorly controlled diabetes (Hgb A1C \>9).
* Active or symptomatic viral hepatitis or Chronic liver disease, including Child-Pugh Class B and C liver disease.
* History of pituitary or adrenal dysfunction.
* Clinically significant heart disease as evidenced by:

  1. myocardial infarction, or
  2. arterial thrombotic events in the past 6 months,
  3. severe or unstable angina, or
  4. New York Heart Association Class III-IV heart disease, or
  5. cardiac ejection fraction measurement of \<50% at baseline.
* Consumption of food or beverages containing grapefruit juice within 7 days of study drug dosing
* Use of a first-generation anti-androgen such as:

  1. bicalutamide within 6 weeks of study drug dosing, or
  2. flutamide within 4 weeks of study dosing.
* 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.