Phase II Trial to Assess the Activity of Ketoconazole Plus Lenalidomide in Patients With Prostate Cancer Progressive After Androgen Deprivation

Inclusion Criteria

PATIENTS WITH PROSTATE CANCER PROGRESSIVE AFTER ANDROGEN DEPRIVATION Inclusion Criteria
Understand and voluntarily sign an informed consent form. Age 18 years at the time of
signing the informed consent form. Histologically confirmed adenocarcinoma of the
prostate. Testosterone less than 50 ng/dL. Patients must continue primary androgen
deprivation with an LHRH analogue if they have not undergone orchiectomy. All previous
cancer therapy, including radiation, and surgery, must have been discontinued at least 4
weeks prior to receive first dose of study drug.

Progressive disease after androgen deprivation.

Exclusion Criteria Prior systemic chemotherapy for hormone refractory prostate cancer.
Prior neoadjuvant and adjuvant chemotherapy are allowed when completed at least 12 months
prior to enrollment.

Prior ketoconazole, aminoglutethimide or corticosteroids for the treatment of progressive
prostate cancer.

Prior immunotherapy including, but not limited to, vaccines, Thalidomide, and or
Lenalidomide like agents.

Supplements or complementary medicines/botanicals are not permitted while on protocol
therapy, except for any combination of the following:

conventional multivitamin supplements selenium lycopene soy supplements Patients should
review the label with their doctor prior to enrollment, and discontinue disallowed agents
prior to study enrollment Serious intercurrent infections or non-malignant medical
illnesses including autoimmune disorders that are uncontrolled.

Psychiatric illnesses/social situations that would limit compliance with protocol
requirements.

Evidence of CNS (brain or Leptomeningeal) metastases or large pleural/pericardial
effusions.

Known contraindication to receive Ketoconazole or Lenalidomide Concurrent use of
ketoconazole with statin compounds is absolutely contraindicated. Thus, patients receiving
Statin drugs (fluvastatin, atorvastatin, and simvastatin) should discontinue them for at
least 7 days before starting ketoconazole.

Patients taking astemizole, terfenadine, or cisapride, rifampin or isoniazid are not
eligible, unless they agreed to completely discontinue those agents. In that case, any
of these agents should be discontinued at least 7 days prior to start therapy with
Ketoconazole.

Use of any other experimental drug or therapy within 28 days of baseline. Known
hypersensitivity to thalidomide or its analogues. Any prior use of Lenalidomide. Known
positive for HIV or infectious hepatitis, type A, B or C. Disease free of prior
malignancies for 5 years with exception of currently treated basal cell, squamous cell
carcinoma of the skin, or carcinoma "insitu" of the breast.