A Randomized Phase II Study of Intermittent Chemotherapy or Intermittent Chemotherapy With Maintenance GM-CSF in Patients With Previously Untreated Hormone Refractory Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 125
- 试验地点
- 4
- 主要终点
- Time to Progression
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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)
- •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
排除标准
- •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
研究组 & 干预措施
Docetaxel + Observation
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
干预措施: Docetaxel (Drug)
Docetaxel + 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)
干预措施: Docetaxel and GM-CSF (Drug)
结局指标
主要结局
Time to Progression
时间窗: 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
次要结局
- Cumulative Duration of Time on and Off Docetaxel-based Therapy(Up to 7 years)
- Number of Participants With PSA Response to Successive Series of Chemotherapy(Up to 6 years)
- Overall Survival(Up to 7 years)