Antiandrogen Withdrawal in Treating Patients With Hormone-Refractory Prostate Cancer
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| ClinicalTrials.gov Identifier: NCT00002760 |
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Recruitment Status :
Completed
First Posted : July 19, 2004
Last Update Posted : June 28, 2016
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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 or disease | Intervention/treatment | Phase |
|---|---|---|
| Prostate Cancer | Drug: ketoconazole Drug: therapeutic hydrocortisone Other: Withdrawal of antiandrogen therapy | Phase 3 |
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).
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 260 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (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 |
| Study Start Date : | August 1996 |
| Actual Primary Completion Date : | March 2004 |
| Actual Study Completion Date : | April 2009 |
| Arm | Intervention/treatment |
|---|---|
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Antiandrogen withdrawal
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
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Other: Withdrawal of antiandrogen therapy
no drugs given |
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Active Comparator: Antiandrogen withdrawal + therapy
Ketoconazole and hydrocortisone
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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 |
- 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
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| Ages Eligible for Study: | up to 120 Years (Child, Adult, Older Adult) |
| Sexes 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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 |
Other Publications:
| Responsible Party: | Alliance for Clinical Trials in Oncology |
| ClinicalTrials.gov Identifier: | NCT00002760 |
| Other Study ID Numbers: |
CALGB-9583 U10CA031946 ( U.S. NIH Grant/Contract ) CLB-9583 CDR0000064708 ( Registry Identifier: NCI Physician Data Query ) |
| First Posted: | July 19, 2004 Key Record Dates |
| Last Update Posted: | June 28, 2016 |
| Last Verified: | June 2016 |
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adenocarcinoma of the prostate recurrent prostate cancer |
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Prostatic Neoplasms Genital Neoplasms, Male Urogenital Neoplasms Neoplasms by Site Neoplasms Prostatic Diseases Ketoconazole Hydrocortisone Hydrocortisone 17-butyrate 21-propionate Hydrocortisone acetate Hydrocortisone hemisuccinate Androgen Antagonists |
Anti-Inflammatory Agents Antifungal Agents Anti-Infective Agents 14-alpha Demethylase Inhibitors Cytochrome P-450 Enzyme Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Steroid Synthesis Inhibitors Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Cytochrome P-450 CYP3A Inhibitors |