Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

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Symptoms and General Pathology

Prostatic Neoplasms

Adenocarcinoma

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Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

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Hydrocortisone

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Ketoconazole

Hydrocortisone-17-butyrate

Androgens

Clotrimazole

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Enzyme Inhibitors

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Hormone Antagonists

Cytochrome P-450 CYP3A Inhibitors

antiandrogen therapy withdrawn; patient who progress will be "crossed over" to Arm 1A: 400 mg ketoconazole PO tid and hydrocortisone 30 mgs PO q am and 10 mgs PO qhs until treatment is no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

400 mg PO tid for as long as treatment is effective

ketoconazole

hydrocortisone 30 mg PO q am and 10 mg PO qhs for as long as treatment is effective

therapeutic hydrocortisone

Withdrawal of antiandrogen therapy

Eric Small, MD

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).

Antiandrogen Withdrawal in Treating Patients With Hormone-Refractory Prostate Cancer

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

Circulating prostate cancer cells as detected by rt-PCR will be correlated with outcomes

Adrenal androgen synthesis suppression will be assessed vs response

National Cancer Institute (NCI)

Alliance for Clinical Trials in Oncology

Spots Global Cancer Trial Database for withdrawal of antiandrogen therapy