Dose Finding Study of Aerosolized GM-CSF in the Treatment of Metastatic Melanoma to the Lung
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 87
- 主要终点
- Progression-free survival
研究概览
简要总结
RATIONALE: Inhaling sargramostim may interfere with the growth of tumor cells and may be an effective treatment for melanoma that has spread to the lung.
PURPOSE: This phase I trial is studying the side effects and best dose of inhaled sargramostim in treating patients with melanoma that is metastatic to the lung.
详细描述
OBJECTIVES:
- Determine immunomodulatory effects of aerosolized sargramostim (GM-CSF) in patients with metastatic melanoma to the lung (part A).
- Determine toxicity profile of this therapy, in terms of pulmonary and hematologic toxicity, in these patients.
- Determine, preliminarily, the therapeutic effects of this therapy, in terms of progression-free survival, overall survival, and objective response rate, in these patients.
- Determine the maximum tolerated dose of GM-CSF in these patients (part B).
OUTLINE: This is a dose-escalation, multicenter study.
Patients receive aerosolized sargramostim (GM-CSF) twice a day on days 1-7 and 15-21. Treatment repeats every 28 days for 2 courses. Patients with no disease progression after completion of course 2 may continue on treatment until disease progression. Patients are grouped to 1 of 2 dose-escalation regimens (part A vs B).
- Part A: Cohorts of 5-10 patients receive escalating doses of GM-CSF until the optimal immunostimulatory dose (ISD) is determined. The optimal ISD is defined as the dose at which at least 7 of 10 patients experience immunostimulation. Once the optimal ISD is determined, 10 patients receive aerosolized GM-CSF at a dose halfway between the optimal ISD and the preceding dose. Dose escalation is discontinued if at least 2 of 5 or at least 4 of 10 patients on a particular dose level experience dose-limiting toxicity.
- Part B: Cohorts of 3-6 patients receive escalating doses of GM-CSF until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed metastatic melanoma to the lung for which no known standard therapy exists
- •At least 1 unidimensionally measurable lesion
- •HLA-A2 positive (part A patients only)
- •Previously treated CNS metastases allowed provided there is no evidence of disease progression within the past 3 months
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status:
- •Life expectancy:
- •At least 12 weeks
- •Hematopoietic:
- •Absolute neutrophil count at least 1,000/mm^3
- •Platelet count at least 75,000/mm^3
- •Hemoglobin at least 8.0 g/dL
- •Bilirubin no greater than 2 times upper limit of normal (ULN)
- •AST no greater than 3 times ULN
- •Creatinine no greater than 2.5 times ULN
- •Cardiovascular:
- •No New York Heart Association class III or IV heart disease
- •No pulmonary disease requiring concurrent active therapy (e.g., supplemental oxygen or bronchodilator)
- •FEV_1 at least 65% of predicted and at least 1.5 L
- •Immunologic:
- •No known immunodeficiency state
- •No known autoimmune disease
- •No uncontrolled infection
- •No active psychotic disorder requiring pharmacotherapy
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy:
- •More than 2 weeks since prior biologic therapy
- •More than 2 weeks since prior immunotherapy
- •More than 4 weeks since prior filgrastim (G-CSF) or sargramostim (GM-CSF)
- •No other concurrent biologic therapy or immunotherapy
- •No concurrent G-CSF
- •No concurrent GM-CSF other than study drug
- •Chemotherapy:
- •More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- •No concurrent chemotherapy
- •Endocrine therapy:
- •More than 2 weeks since prior corticosteroids
- •No concurrent glucocorticosteroids
- •Radiotherapy:
- •More than 2 weeks since prior radiotherapy
- •No concurrent radiotherapy
- •Not specified
- •More than 7 days since prior parenteral antibiotics
- •No concurrent parenteral antibiotics
- •No concurrent immunosuppressive agents
排除标准
- 未提供
研究组 & 干预措施
sargramostim
Patients receive aerosolized sargramostim (GM-CSF) twice a day on days 1-7 and 15-21. Treatment repeats every 28 days for 2 courses. Patients with no disease progression after completion of course 2 may continue on treatment until disease progression. Patients are grouped to 1 of 2 dose-escalation regimens (part A vs B).
After completion of study therapy, patients are followed at 3 months, every 2 months for 1 year, and then every 3-4 months for 5 years.
干预措施: sargramostim (Biological)
结局指标
主要结局
Progression-free survival
时间窗: Up to 6 years
次要结局
- Progression-free survival(Up to 6 years)
- Overall survival(Up to 6 years)
- Objective response rate(Up to 6 years)