Clinical Trial Detail

This is a two-arm, randomized Phase II study of intermittent chemotherapy with and without GM-CSF. All patients will receive six 21-day cycles of docetaxel 75 mg/m2 on Day 2 of each cycle and 5 mg prednisone twice a day on Days 1-21. Following six cycles of chemotherapy, eligible subjects will be randomized to no maintenance therapy or to maintenance GM-CSF therapy. The GM-CSF group dose schedule will be 250 mcg/m2 SQ daily Days 15-28 every 28 days. Patients in both groups will continue until disease progression at which time GM-CSF will be discontinued and chemotherapy will again be administered.

Ages Eligible for Study: 18 Years and older

Genders Eligible for Study: Male

- Age over 18 years

- Histologically documented adenocarcinoma of the prostate

- Progressive metastatic prostate cancer

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

- 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

- = 4 weeks since major surgery and fully recovered

- = 4 weeks since any prior radiation with any toxicity attributable to radiation resolved to =grade 1

- = 8 weeks since the last dose of strontium or samarium

- Sexually active patients must agree to use adequate contraception

- Karnofsky Performance Status = 60%

- Life expectancy >12 weeks

- 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:

- Age over 18 years

- Histologically documented adenocarcinoma of the prostate

- =3 cycles of prior docetaxel chemotherapy for metastatic disease permitted prior to enrollment

- Docetaxel must have been administered on an every 3 week schedule

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

- Castrate levels of testosterone <50 ng/mL

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

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

Other eligibility criteria may apply.

- 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.

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

- Peripheral neuropathy >grade 1

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

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

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

- 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

- 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

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

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

Exclusion criteria for late enrolling patients:

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

- Delay of =6 weeks between any 2 chemotherapy cycles prior to enrollment on study

- Cumulative delays =8 weeks between chemotherapy cycles prior to enrollment on study

Other exclusion criteria may apply.