Safety and Efficacy Study of GM-CSF, Thalidomide Plus Docetaxel in Prostate Cancer

As more men are being diagnosed and treated for prostate cancer at an early age, the number
who experiences a rising level of prostate-specific antigen (PSA) after initial treatment is
increasing, affecting approximately 50,000 patients each year.

These three drugs are commercially available. Thalidomide is an angiogenesis inhibitor which
blocks the development of new blood vessels. GM-CSF stimulates the body's immune response to
fight cancer. Docetaxel is the most active chemotherapeutic agent in the treatment of
prostate cancer. GM-CSF and thalidomide have proven activity in suppressing PSA values.

This study design offers an opportunity to add cytotoxic therapy (docetaxel) in combination
with an active pathobiologic regimen (GM-CSF plus thalidomide) to eradicate micrometastatic
disease, thus potentially offering a significant delay to clinical failure as measured by a
rise in PSA or radiographic involvement. Additionally, delays in the use of hormone therapy
has the potential to be of significant benefit.

GM-CSF will be administered at a fixed dose 3 days per week by subcutaneous injection for 12
months. Participants will receive a fixed dose of thalidomide orally at bedtime daily
without interruption for 12 months. Docetaxel will be administered intravenously over 1 hour
on week 1 of every cycle (every 3 weeks) for 18 weeks.

Inclusion Criteria:

- Diagnosis of adenocarcinoma of the prostate.

- Failure of local treatments (surgery and/or radiation) as defined by a rising PSA;
demonstrated by at least three consecutive rises in PSA by intervals of at least 4
weeks apart with an absolute change of at least 1 ng/mL. If the confirmatory PSA
(third PSA) is less than the previous screening PSA value, an additional test for
rising PSA will be required to document progression.

- No clinical or radiographic evidence of disease.

- The Zubrod performance status 0-1.

- Prior hormonal therapy in the form of neoadjuvant or adjuvant therapy is allowed as
long as androgen therapy has been completed at least 1 year prior to study entry.

- Adequate hematologic function: absolute granulocytes ≥ 1500/ul, platelets ≥
100,000/ul, hemoglobin ≥ 10 gm/100 ml within 4 weeks prior to study entry.

- Adequate hepatic function: bilirubin ≤ 1.5 mg/dl, liver enzymes ≤ 1.5 ULN within 4
weeks prior to study entry.

- Adequate renal function: creatinine ≤ 1.5 x ULN within 4 weeks prior to study entry.

- Patients treated with bisphosphonate therapy before or after study entry are eligible
to continue in the study.

- Negative bone scan within 6 weeks prior to study entry.

- Negative CT scan or MRI of the abdomen and pelvis within 6 weeks prior to study
entry.

- Negative chest x-ray for metastatic disease within 6 weeks prior to study entry.

- Patients must sign a written informed consent prior to treatment.

Exclusion Criteria:

- Serious intercurrent medical illness including symptomatic heart disease within 6
months.

- Previous or concurrent invasive cancers other than superficial non-melanomatous skin
cancer unless disease-free for at least 5 years.

- Major medical or psychiatric illness which, in the investigator's opinion, would
prevent completion of treatment and would interfere with follow-up.

- History of thromboembolic events (deep venous thrombosis, symptomatic cerebrovascular
events or pulmonary embolism), history of MI, within the last 12 months.

- History of bleeding disorders that would contraindicate Coumadin® (warfarin)
including: esophageal varices and clotting factor defects