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
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).
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
q 8 wks, at cross over (if applic), at progression; q 6 mon in f/u
Eric J. Small, MD
University of California, San Francisco
United States: Food and Drug Administration
|University of Minnesota Cancer Center||Minneapolis, Minnesota 55455|
|UCSF Cancer Center and Cancer Research Institute||San Francisco, California 94115-0128|