Finite Androgen Ablation With or Without Abiraterone Acetate and Prednisone in Treating Participants With Recurrent Prostate Cancer

PRIMARY OBJECTIVES:

I. To evaluate whether finite maximal androgen ablation (8 month), as compared to
luteinizing-hormone-releasing hormone (LHRH) alone, will improve one-year post-treatment
prostate specific antigen (PSA)-free survival by 20%.

SECONDARY OBJECTVIES:

I. To determine testosterone recovery difference between the two groups. II. Calculate the
PSA-free survival following testosterone recovery. III. To determine in the steroid
biosynthesis metabolome, in the blood and bone marrow of patients at baseline, maximum
response (eight months therapy) and upon PSA progression, evidence of minimal residual cancer
(MD Anderson Cancer Center [MDACC] main campus patients only).

IV. To apply technologies in development able to detect presence of cancer cells ("minimal
residual disease") at a clinical study milestone (baseline, completion of therapy and upon
PSA progression).

OUTLINE: Participants are randomized to 1 of 2 arms.

ARM A: Participants receive either leuprolide acetate via injection every month or every 4
months, goserelin acetate via injection every month, or degarelix via injection every month
for 8 months. Participants also receive bicalutamide orally (PO) once daily (QD), flutamide
PO three times daily (TID), or nilutamide PO QD. Participants may crossover to Arm B with
disease progression after 8 months.

ARM B: Participants receive leuprolide acetate, goserelin acetate, degarelix, bicalutamide,
flutamide, or nilutamide as in Arm A. Participants also receive abiraterone acetate PO daily
for 8 months and prednisone daily. Participants may crossover to Arm A with disease
progression after 8 months.

After completion of study treatment, participants are followed up every 3 and 6 months.

Inclusion Criteria:

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

- 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

- Life expectancy >= 12 months

- ECOG Performance Status (PS) =< 2

- Histologically documented diagnosis of adenocarcinoma of the prostate (PCa) with no
histologic variants

- Prostate cancer recurrence after definitive local therapy (radical prostatectomy
and/or radiation therapy) as evidenced by rising serum PSA, without evidence of
metastases by bone scan or computed tomography (CT) scan. a) After radiation: A rising
PSA taken to indicate recurrent prostate cancer in patients with previous definitive
external beam radiotherapy will be defined as PSA of 1.0, b) After Radical
Prostatectomy: A rising PSA taken to indicate recurrent prostate cancer in patients
with previous radical prostatectomy will be defined by the criteria of the American
Urological Association as any PSA measurement of 0.2, with a subsequent measurement
>0.2 ng/mL

- Patients who have received androgen ablative therapy for less than 8 weeks immediately
prior to initiation of study drug are eligible provided they had only PSA evidence of
progression (as defined above) with no visible metastases by CT-scan and bone scan
(within 6 weeks) prior to starting androgen ablation

- White blood cell (WBC) >= 3.5 x 10^9/L

- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L

- Platelets >= 100 x 10^9/L

- Hemoglobin (Hb) >= 9.0 g/dL

- Total bilirubin =< 1.5 x upper limit of normal (ULN)

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 1.5 x the upper
limit of normal

- Serum potassium of >= 3.5 mEq/L

- Serum albumin of >= 3.0 g/dL

- Serum creatinine =< 1.5 x ULN

- Patients must have recovered from prior treatment regimens, e.g. surgery, radiation

- A patient who is sexually active and their partner must agree and use two reliable
barrier forms of contraception (for example, condoms and diaphragm), from first day of
study drug administration until for 1 week after last dose of abiraterone acetate,
unless partner is post-menopausal

- 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

Exclusion Criteria:

- Patients who have received prior hormonal therapy are excluded from the trial, except
for: patients who have received up to 6 months of hormonal therapy as neoadjuvant
therapy before radical prostatectomy or while on radiation therapy, as long as more
than 1 year has elapsed between discontinuation of the neoadjuvant hormonal therapy
and initiation of hormonal treatment for relapsing disease

- Any known metastases

- Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (>= 450 msec)

- 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

- Significant co-morbidity that could affect the safety or evaluability of participants
as assessed by the treating physician and or principal investigator

- Prior therapy with strontium-89, samarium, rhenium-186 etidronate, chemotherapy or
androgen biosynthesis inhibitors for prostate cancer is not allowed. Previous
immunologic, homeopathic, natural, or alternative medicine therapies are acceptable
provided treatment ended greater than 28 days prior to initiation of study drug

- Patients who, in the opinion of the investigator, are unable to comply with the
requirements of the study protocol are not eligible

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

- Active or symptomatic viral hepatitis

- History of pituitary or adrenal dysfunction

- Administration of an investigational therapeutic drug within 30 days of cycle 1 day 1

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

- 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