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Phase III Randomized Study of Antiandrogen Withdrawal Alone vs Antiandrogen Withdrawal plus Ketoconazole and Hydrocortisone for Hormone-Refractory Prostate Cancer
Alternate Title Antiandrogen Withdrawal in Treating Patients With Hormone-Refractory Prostate 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. 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 Expected Enrollment 250Approximately 250 patients will be entered over 3 years to attain 238 eligible patients (including 25-40 minority patients). 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.Published Results Ryan CJ, Halabi S, Ou SS, et al.: Adrenal androgen levels as predictors of outcome in prostate cancer patients treated with ketoconazole plus antiandrogen withdrawal: results from a cancer and leukemia group B study. Clin Cancer Res 13 (7): 2030-7, 2007.[PUBMED Abstract] Ryan CJ, Halabi S, Kaplan E, et al.: Use of adrenal androgen levels to predict response to ketoconazole in patients with androgen independent prostate cancer: results from CALGB 9583. [Abstract] J Clin Oncol 22 (Suppl 14): A-4558, 396s, 2004. Small EJ, Halabi S, Dawson NA, et al.: Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583). J Clin Oncol 22 (6): 1025-33, 2004.[PUBMED Abstract] Halabi S, Small EJ, Hayes DF, et al.: Prognostic significance of reverse transcriptase polymerase chain reaction for prostate-specific antigen in metastatic prostate cancer: a nested study within CALGB 9583. J Clin Oncol 21 (3): 490-5, 2003.[PUBMED Abstract] Halabi S, Small E, Farmer D, et al.: Reverse transcriptase polymerase chain reaction (RT-PCR) for prostate specific antigen (PSA) as a prognostic factor for survival among androgen independent prostate cancer patients (AICaP): a companion study to CALGB 9583. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-700, 2001. Small EJ, Halabi S, Picus J, et al.: A prospective randomized trial of antiandrogen withdrawal alone or antiandrogen withdrawal in combination with high-dose ketoconazole in androgen independent prostate cancer patients: results of CALGB 9583. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-695, 2001. Vogelzang NV, Halabi S, Picus J, et al.: Prospective assessment of adrenal androgen levels as predictors of survival in androgen independent prostate cancer patients treated with ketoconazole: a correlative study to CALGB protocol 9583. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-749, 2001. Related PublicationsD'Amico AV, Halabi S, Vogelzang NJ, et al.: A reduction in the rate of PSA rise following chemotherapy in patients with metastatic hormone refractory prostate cancer (HRPC) predicts survival: results of a pooled analysis of CALGB HRPC trials. [Abstract] J Clin Oncol 22 (Suppl 14): A-4506, 383s, 2004. Halabi S, Small EJ, Kantoff PW, et al.: Prognostic model for predicting survival in men with hormone-refractory metastatic prostate cancer. J Clin Oncol 21 (7): 1232-7, 2003.[PUBMED Abstract] Gilligan TD, Halabi S, Kantoff PW, et al.: African-American race is associated with longer survival in patients with metastatic hormone-refractory prostate cancer (HRCaP) in four randomized phase III Cancer and Leukemia Group B (CALGB) trials. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-725, 2002. Trial Lead Organizations Cancer and Leukemia Group B
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. |
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