RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Drugs such as aminoglutethimide or ketoconazole may stop the adrenal glands from producing hormones. Combining hydrocortisone with either aminoglutethimide or ketoconazole may be an effective treatment for prostate cancer. PURPOSE: Phase II trial to study the effectiveness of combining hydrocortisone with either aminoglutethimide or ketoconazole in treating patients who have localized stage IV prostate cancer.

Condition	Treatment or Intervention	Phase
stage IV prostate cancer adenocarcinoma of the prostate recurrent prostate cancer	Drug: aminoglutethimide  Drug: hydrocortisone  Drug: ketoconazole	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the PSA response proportion and duration of response of patients with localized stage IV (D0.5) adenocarcinoma of the prostate treated with early medical adrenalectomy using hydrocortisone combined with aminoglutethimide or ketoconazole after prior antiandrogen withdrawal. II. Compare the incidence of grades 3-4 toxicities of these regimens in these patients. III. Correlate adrenal androgen suppression with response in these patients.

PROTOCOL OUTLINE: Patients are stratified according to prior antiandrogen therapy (yes vs no). Patients with prior antiandrogen therapy begin study therapy after appropriate antiandrogen withdrawal, while those without such prior therapy begin study therapy immediately. Patients undergo medical adrenalectomy using hydrocortisone combined with aminoglutethimide OR ketoconazole. Oral hydrocortisone is administered twice daily. Oral aminoglutethimide is administered twice daily for 1 week and then 4 times daily during subsequent weeks. Oral ketoconazole is administered three times daily. Combination treatment continues in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven adenocarcinoma of the prostate Stage IV (D0.5; no evidence of disease on CT or bone scan after testicular androgen ablation); PSA progression after testicular androgen ablation with or without antiandrogen therapy; Progression is defined as at least 2 consecutive rising PSA levels (drawn at least 2 weeks apart) with a greater than 50% rise above the last nadir level (arbitrary PSA at least 2 ng/dL)

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: Not specified
• Endocrine therapy: See Disease Characteristics; Greater than 4 weeks since prior flutamide (6 weeks for bicalutamide or nilutamide); No prior aminoglutethimide or ketoconazole for prostate cancer; Continuation of primary testicular androgen suppression (i.e., LHRH analog) required
• Radiotherapy: Not specified
• Surgery: Not specified
• Other: No concurrent terfenadine, astemizole, cisapride, or other medicines known to interact with ketoconazole

--Patient Characteristics--

• Age: Not specified
• Performance status: ECOG 0-2
• Life expectancy: Not specified
• Hematopoietic: Not specified
• Hepatic: Not specified
• Renal: Not specified
• Other: No other medical conditions that would increase risk; Fertile patients must use effective contraception

Florida
      H. Lee Moffitt Cancer Center and Research Institute, Tampa,  Florida,  33612-9497,  United States

Study chairs or principal investigators

Mayer Fishman,  Study Chair,  H. Lee Moffitt Cancer Center and Research Institute   

Study ID Numbers:  CDR0000068244; MCC-12219; NCI-G00-1863; MCC-IRB-5722
Record last reviewed:  March 2004
Last Updated:  October 13, 2004
Record first received:  October 4, 2000
ClinicalTrials.gov Identifier:  NCT00006371
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08