Antiandrogen Withdrawal in Treating Patients With Hormone-Refractory Prostate Cancer
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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 | Intervention | Phase |
|---|---|---|
|
Prostate Cancer |
Drug: ketoconazole Drug: therapeutic hydrocortisone Other: Withdrawal of antiandrogen therapy |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study 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 applic), at progression; q 6 mon in f/u ] [ Designated as safety issue: No ]
- Circulating prostate cancer cells [ Time Frame: Pre treatment, 1 time ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]Adrenal androgen synthesis suppression will be assessed vs response
| Enrollment: | 260 |
| Study Start Date: | August 1996 |
| Study Completion Date: | April 2009 |
| Primary Completion Date: | March 2004 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Antiandrogen withdrawal
antiandrogen therapy withdrawn; patient who progess will be "crossed over" to Arm 1A: 400 mg ketoconazole PO tid and hydrocortisone 30 mgs PO q am and 10 mgs PO qhs until treatment is no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
|
Drug: ketoconazole
400 mg PO tid for as long as treatment is effective
Drug: therapeutic hydrocortisone
hydrocortisone 30 mg PO q am and 10 mg PO qhs for as long as treatment is effective
|
Detailed Description:
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).
Eligibility| Genders Eligible for Study: | Male |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| 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 J. Small, MD | University of California, San Francisco |
More Information
Additional Information:
Publications:
| Responsible Party: | Monica M Bertagnolli, MD, Cancer and Leukemia Group B |
| ClinicalTrials.gov Identifier: | NCT00002760 History of Changes |
| Other Study ID Numbers: | CDR0000064708, U10CA031946, CLB-9583 |
| Study First Received: | November 1, 1999 |
| Last Updated: | April 1, 2011 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Cancer and Leukemia Group B:
|
adenocarcinoma of the prostate recurrent prostate cancer |
Additional relevant MeSH terms:
|
Prostatic Neoplasms Genital Neoplasms, Male Urogenital Neoplasms Neoplasms by Site Neoplasms Genital Diseases, Male Prostatic Diseases Androgen Antagonists Cortisol succinate Hydrocortisone acetate Hydrocortisone 17-butyrate 21-propionate Hydrocortisone Hydrocortisone-17-butyrate |
Ketoconazole Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Pharmacologic Actions Anti-Inflammatory Agents Therapeutic Uses Dermatologic Agents 14-alpha Demethylase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antifungal Agents Anti-Infective Agents |
ClinicalTrials.gov processed this record on June 18, 2013