Official Title: “A PHASE III TWO-ARM RANDOMIZED STUDY COMPARING ANTIANDROGEN WITHDRAWAL ALONE VERSUS ANTIANDROGEN WITHDRAWAL COMBINED WITH KETOCONAZOLE AND HYDROCORTISON IN PATIENTS WITH ADVANCED PROSTAGE CANCER”

RATIONALE: Antiandrogen withdrawal may be an effective treatment for prostate cancer.

PURPOSE: Randomized phase III trial to study the effectiveness of ketoconazole and hydrocortisone for antiandrogen withdrawal in treating men with prostate cancer that is refractory to hormone therapy.

Study Type: Interventional

Study Design: Treatment, Randomized

OBJECTIVES: I. Compare the response rate and duration of response to antiandrogen withdrawal alone vs. antiandrogen withdrawal plus ketoconazole/hydrocortisone in patients with advanced hormone-refractory prostate cancer. II. Compare the response rate and duration of response to ketoconazole/hydrocortisone in patients treated with previous vs. simultaneous antiandrogen withdrawal. III. Evaluate the proportion of patients with circulating prostate cancer cells identified by reverse transcriptase-polymerase chain reaction (rt-PCR). IV. Determine whether rt-PCR positively correlates with response. V. Compare the likelihood of response to these regimens in patients whose prior hormonal therapy consisted of initial combined androgen blockage vs. initial monotherapy followed later by an antiandrogen. VI. Correlate adrenal androgen synthesis suppression, as measured by levels of various adrenal androgens, with response.

OUTLINE: Randomized study. Patients who develop progressive disease on Arm I cross to Arm II.

Arm I: Antiandrogen Withdrawal. Antiandrogen stopped. Arm II: Antiandrogen Withdrawal plus Adrenal Androgen Blockade. Antiandrogen stopped; plus Ketoconazole, KCZ; Hydrocortisone, HC, NSC-10483.

PROJECTED ACCRUAL: Approximately 250 patients will be entered over 3 years to attain 238 eligible patients (including 25-40 minority patients).

• DISEASE CHARACTERISTICS: Histologically diagnosed adenocarcinoma of the prostate
• Progressive metastatic or regional nodal disease after at least 4 weeks on flutamide, bicalutamide, or nilutamide, i.e.: Greater than 25% increase in sum of products of perpendicular diameters of all measurable lesions not previously irradiated OR
• Prostate-specific antigen (PSA) at least 5 ng/mL and risen from baseline on at least 2 successive occasions at least 2 weeks apart PSA progression required for "bone only" disease or disease that responded to androgen deprivation and is negative on imaging scans at entry Primary testicular androgen suppression with a luteinizing hormone-releasing hormone (LHRH) analogue plus antiandrogen or by orchiectomy required Intermittent LHRH analog/antiandrogen therapy resumed at least 4 weeks prior to and continued at time of entry LHRH analogue continued throughout study in absence of orchiectomy
• PATIENT CHARACTERISTICS: Age: Any age Performance status: 0-2 Hematopoietic: Not specified
• Hepatic: Bilirubin no greater than 1.5 times normal AST no greater than 3 times normal
• Renal: Not specified Other: No active, uncontrolled condition including: Bacterial, viral, or fungal infection Hyperglycemia Gastric or duodenal ulcer No existing medical condition requiring systemic corticosteroids (inhaled and topical steroids allowed) No concurrent use of the following: Terfenadine Astemizole Cisapride
• PRIOR CONCURRENT THERAPY: No prior therapy with experimental agents for metastatic disease
• Biologic therapy: No prior immunotherapy for metastatic disease Chemotherapy: No prior estramustine or other chemotherapy for metastatic disease Endocrine therapy: See Disease
• Characteristics No prior hormonal therapy for metastatic disease No prior aminoglutethimide
• No prior ketoconazole No prior hydrocortisone or other corticosteroids Prior experimental hormonal therapy requires approval of study chair Radiotherapy: At least 4 weeks since radiotherapy (8 weeks since strontium therapy) Surgery: Orchiectomy allowed

Lead Sponsor: Cancer and Leukemia Group B

UCSF Cancer Center and Cancer Research Institute

San Francisco California 94115-0128 United States

University of Minnesota Cancer Center

Minneapolis Minnesota 55455 United States

Overall Clinical Trial Officials and Contacts

Eric J. Small, MD Study Chair UCSF Helen Diller Family Comprehensive Cancer Center  

Information obtained from ClinicalTrials.gov on July 23, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00002760

Study ID Number: CDR0000064708

ClinicalTrials.gov Identifier: NCT00002760

Health Authority: United States: Federal Government

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