Ketoconazole and Dexamethasone in Prostate Cancer

This is an open label, phase II, single center trial of ketoconazole/dexamethasone to determine if the administration of ketoconazole/dexamethasone, after disease progression with ketoconazole/hydrocortisone slows or reverses disease progression in men with progressive prostate cancer.


Eligibility Criteria:
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.