Ketoconazole and Dexamethasone in Prostate Cancer

Inclusion Criteria: * Histologically confirmed adenocarcinoma of the prostate. * Testosterone \< 50 ng/dL. Participants must continue primary androgen deprivation with an luteinizing hormone-releasing hormone (LHRH) analogue if they have not undergone orchiectomy. * Progressive non-metastatic or metastatic disease after androgen deprivation. Participants must have EITHER: 1. Progression as defined by RECIST criteria. OR 2. Progressive PSA documented within 4 weeks of enrollment. PSA evidence for progressive prostate cancer consists of a PSA level of at least 5 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 first documented rising PSA value, then an additional test for rising PSA will be required to document progression. * Participants who are receiving an antiandrogen as part of primary androgen ablation must demonstrate disease progression following discontinuation of antiandrogen. 1. 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. 2. For participants receiving flutamide, at least one of the PSA values must be obtained 4 weeks or more after flutamide discontinuation. 3. For participants receiving bicalutamide (Casodex) or nilutamide, at least one of the PSA values must be obtained 6 weeks or more after antiandrogen discontinuation. * Karnofsky Performance Status ≥ 60%. * Participants receiving any other hormonal therapy, including any dose of megestrol acetate (Megace), Proscar (finasteride), any herbal product known to decrease PSA levels (e.g., Saw Palmetto and PC-SPES), or any systemic corticosteroid must discontinue the agent for at least 4 weeks prior to enrollment. * Participants on stable doses of bisphosphonates may continue on this medication; further, patients may initiate bisphosphonate therapy at the time of ketoconazole initiation. * Prior radiation therapy completed ≥ 4 weeks prior to enrollment. * Liver function tests (alanine aminotransferase (ALT), aspartate aminotransferase (AST), and Bilirubin) must be within normal limits. * Absolute Neutrophil Count (ANC) \>1500/µl, Platelet count \> 100,00/µl, Creatinine \<1.5 x upper limit of normal (ULN), Hemoglobin \> 8 mg/dl. Exclusion Criteria: * Prior chemotherapy for prostate cancer is not allowed with the exception of cases in which chemotherapy has been administered in a neoadjuvant or adjuvant fashion AND \>1 year has elapsed since the administration of this therapy. * No prior ketoconazole, abiraterone, aminoglutethimide or corticosteroids for treatment of progressive prostate cancer. * No supplements or complementary medicines/botanicals are permitted while on protocol therapy, except for any combination of the following: (conventional multivitamin supplements, selenium, lycopene, soy supplements) No prior radiopharmaceuticals (strontium, samarium) within 8 weeks prior to enrollment. * No "currently active" second malignancy, other than non-melanoma skin cancer. * No serious intercurrent infections or nonmalignant medical illnesses that are uncontrolled. * No psychiatric illnesses/social situations that would limit compliance * No active or uncontrolled autoimmune disease. * No adrenal insufficiency as demonstrated by a baseline adrenocorticotropic hormone (ACTH) stimulation test demonstrating a peak cortisol \>18 µg/dL.