Antiandrogen Withdrawal in Treating Patients With Hormone-Refractory Prostate Cancer
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Prostate Cancer
Intervention: ketoconazole (Drug); therapeutic hydrocortisone (Drug)
Phase: Phase 3
Status: Active, not recruiting
Sponsored by: Cancer and Leukemia Group B Official(s) and/or principal investigator(s):
Eric J. Small, MD, Study Chair, Affiliation: UCSF Helen Diller Family Comprehensive Cancer Center
Summary
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.
Clinical Details
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 design: Treatment, Randomized
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
Minimum age: N/A.
Maximum age: N/A.
Gender(s): Male.
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
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
Locations and Contacts
UCSF Cancer Center and Cancer Research Institute, San Francisco, California 94115-0128, United States
University of Minnesota Cancer Center, Minneapolis, Minnesota 55455, United States
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Related publications: D'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, Kattan MW, Kaplan EB, Dawson NA, Levine EG, Blumenstein BA, Vogelzang NJ. Prognostic model for predicting survival in men with hormone-refractory metastatic prostate cancer. J Clin Oncol. 2003 Apr 1;21(7):1232-7. 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.
Starting date: August 1996
Last updated: May 23, 2008
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