Abiraterone, Radiotherapy and Short-Term Androgen Deprivation in Unfavorable Localized Prostate Cancer

This is a single arm two-site study of 37 men with unfavorable prostate cancer (defined as
having a single high risk factor). Patients will concurrently initiate 6 months of
standard-of-care GNRH agonist therapy and once daily abiraterone acetate/prednisone. After 2
months of lead-in hormonal treatment, definitive standard-of-care prostate/seminal vesicle
radiotherapy will be delivered, to a total dose of 75-80 Gy.

Inclusion Criteria:

- One of the following high risk criteria:

- Gleason Score 7 with PSA ≤ 20 ng/ml and clinical T1-2, or

- Gleason Score 8-10, PSA ≤ 20 ng/ml and clinical T1-2a, or

- PSA 10.1-40 ng/ml with GS < 7 and clinical T1-2, or

- Clinical T3 with Gleason Score < 7 and PSA ≤ 10 ng/ml.

- ECOG Performance Status ≤ 1

- Digital rectal exam within 90 days of registration on study

- CBC with differential with adequate bone marrow function defined as follows:

- Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3, Platelets > 100,000/µL and
Hemoglobin ≥ 9g/dL

- Serum potassium ≥ 3.5 mEq/L

- Serum albumin > 3.0 g/dl

- Total bilirubin < 1.5 X of institutional upper limit of normal (ULN)

- AST(SGOT)/ALT(SGPT) < 1.5 X ULN

- Calculated creatinine clearance > 60 mL/min

- Age > 18 years

- Able to swallow a whole tablet and take abiraterone acetate on an empty stomach
(defined as no food for two hours before and one hour after abiraterone acetate
ingestion)

- Ability to understand and sign a written informed consent document

- Written authorization for use and release of health and research study information has
been obtained

- Be willing/able to adhere to the prohibitions and restrictions specified in this
protocol

- Subjects who have partners of childbearing potential must be willing to use a method
of birth control with adequate barrier protections as determined acceptable by the
principal investigator during the study and for 1 week after the last dose of
abiraterone acetate.

Exclusion Criteria:

- Bone, visceral or soft tissue metastasis, including lymph nodes (>2 cm in longest
diameter)

- Prior therapy for prostate cancer [Exceptions: LHRH agonist or antagonist may have
been initiated within 30 days prior to enrollment. Bicalutamide may have been given
within 60 days of enrollment as long as it has been stopped at least 7 days before
enrollment and total duration was no longer than 30 days. This is to allow enrollment
of those who have been given bicalutamide as a bridge for LHRH agonist/antagonist. It
is highly unlikely a short non-overlapping course of bicalutamide will interact with
abiraterone acetate in a measurable way. Previous alpha-reductase inhibitor use
allowed IF patient has not been taking for at least 30 days prior to abiraterone
acetate initiation, OR if alpha reductase inhibitor was not used as a primary
treatment of prostate cancer and the PSA on alpha-reductase inhibitor remains within
eligibility when doubled. ]

- Known serum testosterone ≤ 150 ng/dl or symptoms of hypogonadism (fatigue, hot
flashes, hair loss, loss of muscle mass, osteoporosis, low libido, depression) prior
to ADT initiation not explained by other medical co-morbidity OR history of
testosterone supplement. If questionable, serum testosterone level greater than 150
ng/dl can be used to exclude hypogonadism.

- Previous malignancy within 3 years other than non-melanomatous skin cancer and
non-muscle invasive bladder cancer

- Previous pelvic radiotherapy that would prevent prostate/SV irradiation

- 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 therapy

- History of gastrointestinal disorders that may interfere with the absorption of study
drug (including gastric bypass surgery)

- Concurrent spironolactone use

- Significant concurrent medical condition that would make prednisone/prednisolone use
contraindicated or would interfere with the patient's ability to participate in the
trial

- Receiving any investigational agents currently or within 30 days prior to study
screening

- Prior demonstrated hypersensitivity, intolerance or allergy to abiraterone acetate,
prednisone or their excipients

- Active co-morbidity, defined as follows:

- Chronic liver disease with cirrhosis (Child-Pugh B or C) or active hepatitis B or
C

- History of pituitary or adrenal dysfunction

- Poorly controlled diabetes mellitus (A1c >9% or history of complications
including peripheral neuropathy, end organ damage, hospitalization, amputation)

- Poorly controlled glaucoma

- 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 III-IV heart disease or known cardiac
ejection fraction measurement of < 50% at baseline.

- Clinical evidence of active infection of any type, including active or
symptomatic viral hepatitis.

- Known immune deficiency and/or HIV-positive patients

- Any medical condition that warrants long-term corticosteroid use in excess of
study dose

- Patients taking strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin,
rifabutin, rifapentine, phenobarbital)

- Any condition that in the opinion of the Principal Investigator, would compromise the
well-being of the subject or the study or prevent the subject from meeting or
performing the study requirements