This phase II trial studies the side effects and how well abiraterone acetate, prednisone, and leuprolide acetate or goserelin before and during radiation therapy works in treating patients with localized or locally advanced prostate cancer. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as abiraterone acetate, leuprolide acetate, and goserelin, may lessen the amount of androgens made by the body. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving abiraterone acetate and leuprolide acetate or goserelin before or together with radiation therapy may be an effective treatment for prostate cancer.

PRIMARY OBJECTIVES:

I. To evaluate the safety of abiraterone (abiraterone acetate) and prednisone with luteinizing hormone-releasing hormone agonist given as neoadjuvant and concurrent therapy with external beam radiation in patients with localized prostate cancer.

II. To determine whether pharmacologic suppression of the prostatic androgen axis by inhibition of androgen production with abiraterone can decrease tissue androgen levels to below those observed with gonadotropin-releasing hormone (GnRH) agonist suppression of testicular androgens.

SECONDARY OBJECTIVES:

I. To determine whether treatment with abiraterone acetate with luteinizing releasing hormone agonist will be more effective than agonist with bicalutamide in inducing inhibition of androgen-regulated gene expression and increased apoptotic cell death as assessed by immunohistochemistry, complementary deoxyribonucleic acid (cDNA) microarray analysis and reverse transcription-polymerase chain reaction (RT-PCR).

II. To evaluate time to prostate-specific antigen progression in patients treated with GnRH agonist with abiraterone acetate.

OUTLINE:

Patients receive abiraterone acetate orally and prednisone once daily for 24 weeks. Patients also receive leuprolide acetate or goserelin in weeks 1 and 13. Patients undergo external beam radiotherapy starting in week 15 for 8.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 5 years.

Inclusion Criteria:

• Willing and able to provide written informed consent

• Patients must allow biopsy prior to neoadjuvant therapy and at the time of fiducial placement

• Written Authorization for Use and Release of Health and Research Study Information has been obtained

• Histologically proven adenocarcinoma of the prostate

• Patients must be candidates for short or long term androgen deprivation in combination with external beam radiotherapy (RT) based on the following criteria:

  • Intermediate Risk Disease: T2b/c, or Gleason 7, or Prostate Specific Antigen 10-20
  • High Risk Disease: Gleason 8-10, or Prostate specific antigen> 20, or T3/4

• Patients may not have received any prior pharmacologic therapy or radiation therapy (RT) for prostate cancer

• Eastern Cooperative Oncology Group (ECOG) performance status =< 2

• Karnofsky >= 60%

• Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the androgen axis will be determined following review of their case by the Principal Investigator

• White blood cell count: >= 3,000/mm^3

• Absolute granulocyte count: >= 1,000/mm^3

• Platelets: >= 100,000/mm^3

• Hemoglobin >= 10g/dL

• Potassium >= 3.5 mmol/L

• Serum creatinine: =< 1.5 x upper limit of normal (ULN)

• Aspartate aminotransferase (AST) < 2.5 x ULN

• Alanine transaminase (ALT) < 2.5 x ULN

• Total bilirubin: =< 1.5 x ULN (except for patients with documented Gilbert's disease)

Exclusion Criteria:

• Patients may not be receiving any investigational agents
• Concurrent enrollment in another clinical investigational drug or device study is prohibited
• The concurrent administration of other anticancer therapy, including cytotoxic or hormonal agents (except Luteinizing hormone releasing hormone agonists), or immunotherapy, is prohibited during neoadjuvant concurrent and adjuvant therapy
• Patients who are currently receiving active therapy for other neoplastic disorders will not be eligible
• Patients with histologic evidence of small cell carcinoma of the prostate will not be eligible
• Patients with hypogonadism or severe androgen deficiency as defined by serum testosterone less than 100 ng/dL will not be eligible
• History of pituitary or adrenal dysfunction
• Patients who are receiving any androgens, estrogens or progestational agents, or who received any of these agents within the 6 months prior to evaluation will not be eligible
• Patients who are taking drugs which affect androgen metabolism (e.g. spironolactone, ketoconazole, finasteride, dutasteride) will not be eligible
• Concomitant therapy with any of the following listed is prohibited: 5 alpha-reductase inhibitor (finasteride, dutasteride); ketoconazole, diethylstilbestrol, and other preparations such as saw palmetto thought to have endocrine effects on prostate cancer; radiopharmaceuticals such as strontium (89Sr) or samarium (153Sm); Aldactone, Spironol (spironolactone); estrogens, testosterone, progesterones, herbal medications
• Patients who received any of these agents within the 6 months prior to evaluation will be reviewed for eligibility by the Principal Investigator on a case by case basis
• Use of other investigational drug therapy for any reason is prohibited
• Patients with inflammatory bowel disease or other autoimmune conditions which might affect the radiated colon or rectum
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, cardiac arrhythmia which is symptomatic or requires active therapy, recent deep venous thrombosis, pulmonary emboli, cerebrovascular accident or ischemia will not be eligible
• Patients who have chronic active hepatitis or acute hepatitis will not be eligible
• Patients with dementia/psychiatric illness/social situations that would limit compliance with study requirements or would prohibit the understanding and/or giving of informed consent will not be eligible
• Patients with medical conditions, which, in the opinion of the investigators, would jeopardize either the patient or the integrity of the data obtained will not be eligible
• Uncontrolled hypertension within the screening period (systolic blood pressure [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 congestive heart failure of any severity
• Other active malignancy, except non-melanoma skin cancer and superficial bladder cancer
• History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug
• Patients with diabetes not controlled with diet alone (i.e. requiring insulin or oral hypoglycemics)
• Patients unwilling to use contraceptives while on study