Treating Patients With Prostate Cancer That Did Not Respond to Hormone Therapy

OBJECTIVES:

Primary

- Determine the objective response frequency in patients with hormone-refractory
progressive prostate cancer treated with ketoconazole, hydrocortisone, and lenalidomide.

Secondary

- Determine the effect of this regimen on time to clinical progression in these patients.

- Determine the safety of this regimen in these patients.

- Determine the effects of this regimen on serum cytokines, including tumor necrosis
factor-alpha, basic fibroblast growth factor, plasma soluble interleukin (IL)-2
receptor, IL-8, and IL-12, as well as serum vascular endothelial growth factor levels in
these patients.

- Determine the co-stimulatory effects of this regimen on dendritic cells and
CD4-positive, CD25-positive, T-regulatory cells in these patients.

OUTLINE: This is a nonrandomized, open-label study.

Patients receive oral ketoconazole 3 times daily and oral hydrocortisone twice daily on days
1-28 and oral lenalidomide once daily on days 1-21. Courses repeat every 28 days in the
absence of disease progression or unacceptable toxicity.

Patients undergo blood collection periodically during study for evaluation of prostate
cancer-specific immune response. Blood samples are assessed by serum analysis, flow
cytometry, real-time PCR, and enzyme-linked immunosorbent assay techniques to detect and
quantify different cytokines, antiangiogenic markers, dendritic cells, and specific
T-regulatory cells.

After completion of study therapy, patients are followed at 30 days.

PROJECTED ACCRUAL: A total of 34 patients will be accrued for this study.

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.