Use of Low Dose Ketoconazole in Prostate Cancer That Does Not Respond to Hormone Therapy and Prior Chemotherapy

The aim of the study is to research the response of low dose ketoconazole in hormone
refractory prostate cancer (HRPC) patients who have already undergone chemotherapy as part
of their prostate cancer treatment. The hypothesis of the study is that HRPC patients who
have been previously treated with chemotherapy will demonstrate objective PSA response rates
to low dose ketoconazole, comparable to historical response rates reported in
chemotherapy-naïve patients. This is a single arm trial, with all participants given
ketoconazole 200mg TID, along with hydrocortisone given at 20mg in the morning, 10mg at
night daily. Each cycle will consist of 28 days. The subject's study participation will
continue until subject experiences disease progression, unacceptable toxicities, withdraws
consent for the study or dies.

Inclusion Criteria:

- Patients must have histologically or cytologically proven prostate cancer with a
Gleason score available or interpretable.

- Patients must have prostate cancer deemed to be hormone refractory, by progression of
measurable or evaluable disease or rising PSA.

- Patients must be >18 years old

- Patients must have received at least one prior chemotherapy regimen >3 weeks prior to
initiation of study and patients must have recovered from the side effects of the
therapy

- Patients must have an ECOG status of 0-3

- Patients must have normal organ and marrow function, determined within 14 days of
registration.

- Patients must have been surgically or medically castrated. If the method of
castration was LHRH agonists (leuprolide or goserelin), then the patient must be
willing to continue the use of LHRH agonists.

- Patients must have a serum total testosterone level <50 ng/dl

- If the patient has been treated with non-steroidal anti-androgens (flutamide,
bicalutamide or nilutamide) or other hormonal treatment (megace or steroids), the
patient must have stopped these agents at least 28 days prior to enrollment for
flutamide, megace or steroids and at least 42 days prior to enrollment for
bicalutamide or nilutamide; and the patients must have demonstrated progression of
disease since the agents were suspended.

Exclusion Criteria:

- Patients with any condition that impairs the ability to swallow medications orally

- Patients who are unable to give informed consent

- Patients who have received ketoconazole treatment for prostate cancer in the past

- Patients with other active malignancies in the past 3 years except nonmelanoma skin
cancer

- Patients may not be receiving any other investigational agents

- Patients with known hypersensitivity to ketoconazole

- Patients may not be taking certain medications, including terbinafine, astemizole,
triazolam, statins (except pravastatin and fluvastatin) and acid suppressive agents
(antacids, H2 blockers, PPI) while on ketoconazole, and patients on these medications
must agree to discontinue these medications and consider alternative therapies.