A Phase II Study of Increased-Dose Abiraterone Acetate in Patients With Castration Resistant Prostate Cancer (CRPC)

Inclusion Criteria:

- Have signed an informed consent document indicating that the subjects understands the
purpose of and procedures required for the study and are willing to participate in
the study

- Be willing/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

- Male aged 18 years and above

- Able to swallow the study drug whole as a tablet

- Willing to take abiraterone acetate on an empty stomach; 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 who have partners of childbearing potential must be 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
study drug administration.

- Have a baseline serum potassium of ≥ 3.5 mEq/L

- Have aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin
levels < 1.5 x ULN

- Have a serum albumin of ≥ 3.0 g/dL

- Total bilirubin ≤ 1.5 x ULN (In patients with known Gilbert Syndrome, a total
bilirubin ≤ 3.0 x ULN, with direct bilirubin ≤ 1.5 x ULN is acceptable)

- Have a platelet count of ≥ 100,000/μL

- Have an absolute neutrophil count of > 1500 cell/mm3

- Have a calculated creatinine clearance ≥ 60 mL/min

- Have a hemoglobin of ≥ 9.0 g/dL

- Have histologically confirmed adenocarcinoma of the prostate.

- No prior therapy with chemotherapy for metastatic prostate cancer.

- Have metastatic disease based on a positive bone scan or objective imaging on CT
scan.

- Have ongoing gonadal androgen deprivation therapy with LHRH analogues or orchiectomy.
Patients who have not had an orchiectomy must be maintained on effective LHRH
analogue therapy for the duration of the trial.

- Testosterone < 50 ng/dL.

- Progressive disease after androgen deprivation: PSA evidence for progressive prostate
cancer consists of a PSA level of at least 2 ng/ml which has risen on at least 2
successive occasions, at least 2 weeks apart. If the confirmatory PSA value is less
than the screening PSA value, then an additional test for rising PSA will be required
to document progression.

- Antiandrogen Withdrawal Patients who are receiving an antiandrogen as part of primary
androgen ablation must demonstrate disease progression following discontinuation of
antiandrogen.

- Disease progression after antiandrogen withdrawal is defined as 2 consecutive rising
PSA values, obtained at least 2 weeks apart, or documented osseous or soft tissue
progression.

- For patients receiving flutamide, at least one of the PSA values must be obtained 4
weeks or more after flutamide discontinuation.

- For patients receiving bicalutamide or nilutamide, at least one of the PSA values
must be obtained 6 weeks or more after antiandrogen discontinuation.

- No antiandrogen withdrawal response is expected in patients in whom antiandrogen
therapy did NOT result in a decline in PSA or in those patients in whom the response
to antiandrogens was < 3 months. Therefore, it is not necessary to wait for AAWD in
pts without PSA decline on an anti-androgen or in those in whom a PSA response lasted
< 3 months.

- ECOG Performance Status 0-1

- Life expectancy of ≥ 12 weeks.

Exclusion Criteria:

- Active infection or other medical condition that would make prednisone/prednisolone
(corticosteroid) use contraindicated

- Known brain metastasis

- Uncontrolled hypertension (systolic BP ≥ 160 mmHg or diastolic BP ≥ 95 mmHg) Patients
with a history of hypertension are allowed provided blood pressure is controlled by
anti-hypertensive treatment

- Active or symptomatic viral hepatitis or chronic liver disease

- History of pituitary or adrenal dysfunction

- 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 II-IV heart disease or cardiac ejection fraction
measurement of < 50 % at baseline

- Atrial Fibrillation, or other cardiac arrhythmia requiring medical therapy

- Administration of an investigational therapeutic within 30 days of screening

- Have poorly controlled diabetes

- Have a history of gastrointestinal disorders (medical disorders or extensive surgery)
that may interfere with the absorption of the study agents

- Have a pre-existing condition that warrants long-term corticosteroid use in excess of
study dose

- Have known allergies, hypersensitivity, or intolerance to abiraterone acetate or
prednisone or their excipients

- Any condition which, in the opinion of the investigator, would preclude participation
in this trial.

- Pure small cell carcinoma of the prostate or any mixed histology cancer of the
prostate (eg: neuroendocrine) which contains < 50% adenocarcinoma.

- Therapy with other hormonal therapy, including any dose of megestrol acetate
(Megace), finasteride (Proscar), dutasteride (Avodart) any herbal product known to
decrease PSA levels (e.g., Saw Palmetto and PC-SPES), or any systemic corticosteroid
within 4 weeks prior to first dose of study drug.

- Prior therapy with Abiraterone Acetate or other CYP17 inhibitor(s) including TAK-700
or TOK-001, or investigational agent(s) targeting the androgen receptor for
metastatic prostate cancer.

- Prior therapy with ketoconazole for > 2 weeks for prostate cancer.

- Therapy with supplements or complementary medicines/botanicals within 4 weeks of
first dose of study drug, except for any combination of the following:

- Conventional multivitamin supplements

- Selenium

- Lycopene

- Soy supplements

- Prior radiation therapy completed < 4 weeks prior to enrollment

- Prior chemotherapy for castration resistant prostate cancer. Patients who have
received chemotherapy for early stage prostate cancer (e.g. as part of a neoadjuvant
or adjuvant trial) or for other malignancies are eligible provided that >1 year has
passed since the administration of the last chemotherapy dose.

- Any "currently active" second malignancy, other than non-melanoma skin cancer.
Patients are not considered to have a "currently active" malignancy, if they have
completed therapy and are considered by their physician to be at least less than 30%
risk of relapse over next year.

- Active psychiatric illnesses/social situations that would limit compliance with
protocol requirements.

- Patients in whom urgent chemotherapy, in the opinion of the treating physician, is
indicated should not be enrolled in this study.