A Randomized Phase II Study of Intermittent Chemotherapy or Intermittent Chemotherapy With Maintenance GM-CSF in Patients With Previously Untreated Hormone Refractory Prostate Cancer

Inclusion Criteria:

1. Age over 18 years

2. Histologically documented adenocarcinoma of the prostate

3. Progressive metastatic prostate cancer

4. Castrate levels of testosterone (<50 ng/ml) must be maintained

5. Prior hormonal therapy or medications :

Patients who are receiving an anti-androgen, secondary hormonal therapy (i.e.
ketoconazole, aminoglutethimide, megestrol acetate, diethylstilbestrol), 5-alpha
reductase inhibitor (i.e. finasteride (Proscar), dutasteride (Avodart)) or herbal
prostate medication (i.e. saw palmetto, PC-SPES, PC-PLUS) must discontinue the drug
by the date of initiation of chemotherapy on study

6. ≥ 4 weeks since major surgery and fully recovered

7. ≥ 4 weeks since any prior radiation with any toxicity attributable to radiation
resolved to ≤grade 1

8. ≥ 8 weeks since the last dose of strontium or samarium

9. Sexually active patients must agree to use adequate contraception

10. Karnofsky Performance Status ≥ 60%

11. Life expectancy >12 weeks

12. Required initial laboratory values Absolute neutrophil count > 1500/ul Platelets
> 100,000/ul Hemoglobin > 8.0 g/dl Creatinine ≤ 2.0 X upper limit of normal
Bilirubin ≤upper limit of normal (ULN)

AST/ALT/alkaline phosphatase:

AST AND ALT AND alkaline phosphatase must be within the range allowing for eligibility In
determining eligibility, the more abnormal of the 2 values (AST or ALT should be used. An
abnormal alkaline phosphatase must be attributed to liver dysfunction and not metastatic
bone involvement (i.e elevated GGTP or evidence of liver metastases)

Inclusion criteria for late enrolling patients:

1. Age over 18 years

2. Histologically documented adenocarcinoma of the prostate

3. ≤3 cycles of prior docetaxel chemotherapy for metastatic disease permitted prior to
enrollment

4. Docetaxel must have been administered on an every 3 week schedule

5. Each docetaxel dose must have been between 60 and 75 mg/m2

6. Castrate levels of testosterone <50 ng/mL

7. Daily use of other steroids (hydrocortisone, dexamethasone) instead of prednisone or
no steroids, is permitted up until time of enrollment

8. A PSA level must have been documented within 6 weeks of initiating docetaxel
chemotherapy

Exclusion Criteria:

1. Prior systemic chemotherapy for prostate cancer, other than q 3-week
docetaxel/prednisone. Prior neoadjuvant or adjuvant chemotherapy is permitted if
there was no evidence of disease relapse within 12 months of the last dose of
chemotherapy.

2. >3 cycles of q3 week docetaxel/prednisone chemotherapy has already been administered
to the patient

3. Peripheral neuropathy >grade 1

4. Prior immunotherapy including systemic GM-CSF or vaccines utilizing GM-CSF; prior
G-CSF support of chemotherapy-related neutropenia is permitted

5. Prior biologic agents (i.e.,anti-angiogenic agents, anti-EGFR inhibitors)≤ 4 weeks
prior to registration

6. More than two prior therapies with an investigational agent, completed ≤ 4 weeks
prior to enrollment (no prior immunotherapeutics are allowed)

7. Myocardial infarction or significant change in anginal pattern within the last 6
months, symptomatic congestive heart failure (NYHA Class III or higher) or
uncontrolled cardiac arrhythmia

8. Because patients with immune deficiency are at increased risk of lethal infections
when treated with marrow-suppressive therapy, HIV-positive patients receiving
combination anti-retroviral therapy are excluded

9. Patients with a history of severe hypersensitivity reaction to docetaxel or other
drugs formulated with polysorbate 80 will be excluded

10. Poorly controlled diabetes (fasting blood glucose >250) despite optimization of
medical therapy

Exclusion criteria for late enrolling patients:

1. Prior immunotherapy including systemic GM-CSF or vaccines utilizing GM-CSF; prior
G-CSF support for chemotherapy-related neutropenia is permitted

2. Delay of ≥6 weeks between any 2 chemotherapy cycles prior to enrollment on study

3. Cumulative delays ≥8 weeks between chemotherapy cycles prior to enrollment on study