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.

Condition	Treatment or Intervention	Phase
adenocarcinoma of the prostate recurrent prostate cancer	Drug: hydrocortisone  Drug: ketoconazole	Phase III

Further Study Details: 

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.

PROTOCOL 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).

Criteria

PROTOCOL ENTRY CRITERIA:

--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

--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

--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

California
      UCSF Cancer Center and Cancer Research Institute, San Francisco,  California,  94115-0128,  United States
Minnesota
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States

Study chairs or principal investigators

Eric J. Small,  Study Chair,  Cancer and Leukemia Group B   

Study ID Numbers:  CDR0000064708; CLB-9583
Record last reviewed:  July 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002760
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08