ketoconazole and dexamethasone in prostate cancer

Conditions: Prostate Cancer

Summary: 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 \ 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.

Keywords: ketoconazole dexamethasone