Official Title: “A Phase II Trial of Early Medical Adrenalectomy for "D0.5" Prostate Cancer”

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.

Study Type: Interventional

Study Design: Treatment

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.

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.

• 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)

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
• 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

Lead Sponsor: H. Lee Moffitt Cancer Center and Research Institute

H. Lee Moffitt Cancer Center and Research Institute

Tampa Florida 33612-9497 United States

Overall Clinical Trial Officials and Contacts

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

Information obtained from ClinicalTrials.gov on July 23, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00006371

Study ID Number: CDR0000068244

ClinicalTrials.gov Identifier: NCT00006371

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database