Antiandrogen Withdrawal in Treating Patients With Hormone-Refractory Prostate 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.
|Prostate Cancer||Drug: ketoconazole Drug: therapeutic hydrocortisone Other: Withdrawal of antiandrogen therapy||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- Response: PSA [ Time Frame: q 8 wks, at cross over (if applicable), at progression; q 6 mon in f/u ]
- Circulating prostate cancer cells [ Time Frame: Pre treatment, 1 time ]Circulating prostate cancer cells as detected by rt-PCR will be correlated with outcomes
- Adrenal androgen synthesis suppression [ Time Frame: pre tx, after 1 and 3 months tx, at progression ]Adrenal androgen synthesis suppression will be assessed vs response
|Study Start Date:||August 1996|
|Study Completion Date:||April 2009|
|Primary Completion Date:||March 2004 (Final data collection date for primary outcome measure)|
antiandrogen therapy withdrawn; patient who progress will be "crossed over" to Arm 1A: 400 mg ketoconazole PO tid and hydrocortisone 30 mgs PO q am and 10 mgs PO qhs until treatment is no longer effective
Other: Withdrawal of antiandrogen therapy
no drugs given
Active Comparator: Antiandrogen withdrawal + therapy
Ketoconazole and hydrocortisone
400 mg PO tid for as long as treatment is effectiveDrug: therapeutic hydrocortisone
hydrocortisone 30 mg PO q am and 10 mg PO qhs for as long as treatment is effective
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).
Please refer to this study by its ClinicalTrials.gov identifier: NCT00002760
|United States, California|
|UCSF Cancer Center and Cancer Research Institute|
|San Francisco, California, United States, 94115-0128|
|United States, Minnesota|
|University of Minnesota Cancer Center|
|Minneapolis, Minnesota, United States, 55455|
|Study Chair:||Eric Small, MD||University of California, San Francisco|