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

Abiraterone acetate and cabazitaxel have been approved by the United States Food and Drug
Administration (FDA) to treat prostate cancer that has spread to other parts of the body such
as the lymph nodes or bone. These drugs are approved individually for use when the cancer has
become resistant to other treatments, including chemotherapy with docetaxel. The combination
of these two drugs has not been evaluated, so the research team will study the safety and
effectiveness of the combination.

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.