Antiandrogen Withdrawal in Treating Patients With Hormone-Refractory Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00002760
Recruitment Status : Completed
First Posted : July 19, 2004
Last Update Posted : June 28, 2016
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

November 1, 1999
July 19, 2004
June 28, 2016
August 1996
March 2004   (Final data collection date for primary outcome measure)
Response: PSA [ Time Frame: q 8 wks, at cross over (if applicable), at progression; q 6 mon in f/u ]
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Complete list of historical versions of study NCT00002760 on Archive Site
  • 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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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.

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).

Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Prostate Cancer
  • 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
  • Other: Withdrawal of antiandrogen therapy
    no drugs given
  • 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
    Intervention: Other: Withdrawal of antiandrogen therapy
  • Active Comparator: Antiandrogen withdrawal + therapy
    Ketoconazole and hydrocortisone
    • Drug: ketoconazole
    • Drug: therapeutic hydrocortisone

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
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April 2009
March 2004   (Final data collection date for primary outcome measure)

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

Sexes Eligible for Study: Male
up to 120 Years   (Child, Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
U10CA031946 ( U.S. NIH Grant/Contract )
CDR0000064708 ( Registry Identifier: NCI Physician Data Query )
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Alliance for Clinical Trials in Oncology
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Study Chair: Eric Small, MD University of California, San Francisco
Alliance for Clinical Trials in Oncology
June 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP