Intermittent Chemotherapy With or Without Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) for Metastatic Hormone Refractory Prostate Cancer (HRPC)
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Docetaxel; Docetaxel and GM-CSF
Intervention description: Docetaxel 75mg/m2 every 21 days; Docetaxel 75mg/m2 every 21 days and GM-CSF 250mcg/m2 SQ days 15-28
Intervention MeSH terms: Docetaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 125.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic Hormone Refractory Prostate Cancer

Summary:

      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 subcutaneous (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.
    

Eligibility criteria:

        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)

        aspartate aminotransferase (AST) / alanine aminotransferase (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 gamma-glutamyl transpeptidase (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 Prostate-specific antigen (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-Epithelial Growth Factor
             Receptor (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