Intermittent Chemotherapy With or Without Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) for Metastatic Hormone Refractory Prostate Cancer (HRPC)
- Registration Number
- NCT00488982
- Lead Sponsor
- University of California, San Francisco
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 125
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Age over 18 years
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Histologically documented adenocarcinoma of the prostate
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Progressive metastatic prostate cancer
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Castrate levels of testosterone (<50 ng/ml) must be maintained
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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
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≥ 4 weeks since major surgery and fully recovered
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≥ 4 weeks since any prior radiation with any toxicity attributable to radiation resolved to ≤grade 1
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≥ 8 weeks since the last dose of strontium or samarium
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Sexually active patients must agree to use adequate contraception
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Karnofsky Performance Status ≥ 60%
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Life expectancy >12 weeks
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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:
- 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 Prostate-specific antigen (PSA) level must have been documented within 6 weeks of initiating docetaxel chemotherapy
- 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-Epithelial Growth Factor Receptor (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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Docetaxel + GM-CSF Docetaxel and GM-CSF Intermittent docetaxel/prednisone with maintenance GM-CSF therapy: Patients will discontinue docetaxel/prednisone and will receive maintenance GM-CSF until disease progression at which time, they will discontinue GM-CSF and resume docetaxel/prednisone. Six cycles of docetaxel/prednisone will again be administered before discontinuation of chemotherapy and GM-CSF therapy is re-initiated. GM-CSF dose/schedule will be as previously described (250 mcg/m2 SQ daily, days 15-28 q28 days) Docetaxel + Observation Docetaxel Intermittent docetaxel/prednisone with no maintenance therapy: Patients will discontinue docetaxel/prednisone and undergo observation until disease progression at which time they will re-initiate docetaxel/prednisone. Six cycles of docetaxel/prednisone will again be administered before subsequent discontinuation of chemotherapy
- Primary Outcome Measures
Name Time Method Time to Progression Up to 7 years The Kaplan-Meier product limit method with 95% confidence intervals will be used to estimate the median time to disease progression during initial course of randomized treatment
- Secondary Outcome Measures
Name Time Method Cumulative Duration of Time on and Off Docetaxel-based Therapy Up to 7 years Median percentage of time will be calculated to summarize the total duration of chemotherapy and amount of docetaxel/prednisone administered while the patient is on study. The same results will be tabulated for each. For the on-chemotherapy period: will be estimated from the date of starting protocol therapy; if a patient received docetaxel on day 2 of a cycle, he will be considered to have received a full 21 days on therapy. For the off-chemotherapy period: will be calculated from the date of starting the observation or GM-CSF period to the date of resuming chemotherapy
Number of Participants With PSA Response to Successive Series of Chemotherapy Up to 6 years PSA partial response is defined by at least a 50% decline from PSA value from the baseline measurement to 12 weeks of protocol therapy. The decline must be confirmed by a second PSA value obtained 4 or more weeks later For those patients whose PSA have decreased but has not reached response criteria defined above, progressive disease is defined as 25% increase over the nadir PSA value provided that the increase is at least 5ng/mL and is confirmed.
Overall Survival Up to 7 years The Kaplan-Meier product limit method will be used to estimate the median overall survival
Trial Locations
- Locations (4)
University of Washington
🇺🇸Seattle, Washington, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of California, San Francisco
🇺🇸San Francisco, California, United States
Oregon Health and Science University Cancer Institute
🇺🇸Portland, Oregon, United States