Antiandrogen Withdrawal in Treating Patients With Hormone-Refractory Prostate Cancer

Phase 3

Completed

• Conditions: Prostate Cancer
• Interventions: Drug: ketoconazole; Other: Withdrawal of antiandrogen therapy; Drug: therapeutic hydrocortisone

• Registration Number: NCT00002760
• Lead Sponsor: Alliance for Clinical Trials in Oncology

Brief 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.

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).

Study Timeline

• Study Start: 1996-08
• Study First Submitted: 1999-11-01
• Primary Completion: 2004-03
• Study First Submitted QC: 2004-07-16
• Study First Posted: 2004-07-19
• Study Completion: 2009-04
• Status Verified: 2016-06
• Last Update Submitted: 2016-06-27
• Last Update Posted: 2016-06-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 260

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Antiandrogen withdrawal + therapy	therapeutic hydrocortisone	Ketoconazole and hydrocortisone
Antiandrogen withdrawal + therapy	ketoconazole	Ketoconazole and hydrocortisone
Antiandrogen withdrawal	Withdrawal of antiandrogen therapy	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

Primary Outcome Measures

Name	Time	Method
Response: PSA	q 8 wks, at cross over (if applicable), at progression; q 6 mon in f/u

Secondary Outcome Measures

Name	Time	Method
Circulating prostate cancer cells	Pre treatment, 1 time	Circulating prostate cancer cells as detected by rt-PCR will be correlated with outcomes
Adrenal androgen synthesis suppression	pre tx, after 1 and 3 months tx, at progression	Adrenal androgen synthesis suppression will be assessed vs response

Trial Locations

Locations (2)

UCSF Cancer Center and Cancer Research Institute; 🇺🇸 San Francisco, California, United States

University of Minnesota Cancer Center; 🇺🇸 Minneapolis, Minnesota, United States