Ketoconazole and Dexamethasone in Prostate Cancer

• Status: Completed
• Trial end date: 2014-10-09
• Target enrollment: 0
• Participant gender: Male

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, San Francisco
• Treatments: BB 1101; Cortisol succinate; Dexamethasone; Dexamethasone 21-phosphate; Dexamethasone acetate; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Ketoconazole

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.