Phase II Trial of Irinotecan/Docetaxel for Advanced Pancreatic Cancer, With Randomization Between Irinotecan/Docetaxel and Irinotecan/Docetaxel Plus C225 a Monoclonal Antibody to the Epidermal Growth Factor Receptor (EGF-r)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 94
- 主要终点
- Proportion of Patients With Objective Response Evaluated by RECIST (Solid Tumor Response Criteria)
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining chemotherapy with cetuximab may kill more tumor cells.
PURPOSE: This randomized phase II trial is studying giving irinotecan and docetaxel together with cetuximab to see how well it works compared to irinotecan and docetaxel alone in treating patients with metastatic pancreatic cancer .
详细描述
OBJECTIVES:
- Determine the efficacy of irinotecan and docetaxel with or without cetuximab, in terms of objective response rate, in patients with metastatic adenocarcinoma of the pancreas.
- Determine the time to progression and overall survival of patients treated with these regimens.
- Determine the proportion of patients with tumors that overexpress epidermal growth factor receptor.
OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.
- Arm A: Patients receive docetaxel IV over 1 hour and irinotecan IV over 30 minutes weekly on days 1, 8, 15, and 22.
- Arm B: Patients receive docetaxel and irinotecan as in arm A. Patients also receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 36.
Courses repeat in both arms every 6 weeks in the absence of disease progression or unacceptable toxicity.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed metastatic adenocarcinoma of the pancreas
- •Sufficient tumor tissue from fine needle aspiration, core biopsy, or open biopsy available for epidermal growth factor receptor testing
- •At least 1 unidimensionally measurable primary or metastatic lesionge
- •Age of 18 and over
- •ECOG performance status 0-1
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Creatinine clearance > 60 mL/min
- •LVEF normal
- •Absolute neutrophil count > 1,500/mm^3
- •Platelet count > 100,000/mm^3
- •Bilirubin ≤ upper limit of normal (ULN)*
- •SGOT or SGPT and alkaline phosphatase must meet the criteria for 1 of the following*:
- •SGOT or SGPT ≤ 2.5 times ULN AND alkaline phosphatase ≤ ULN
- •SGOT or SGPT ≤ 1.5 times ULN AND alkaline phosphatase > ULN but ≤ 2.5 times ULN
- •SGOT or SGPT ≤ ULN AND alkaline phosphatase > 2.5 but ≤ 4 times ULN
- •NOTE: *Percutaneous stenting or endoscopic retrograde cholangiopancreatography may be used to normalize liver function tests
排除标准
- •History of uncontrolled arrhythmias
- •History of congestive heart failure
- •History of uncontrolled angina pectoris
- •Prior chemotherapy
- •Pre-existing neuropathy ≥ grade 2
- •Prior hypersensitivity to polysorbate 80
- •Pregnant or nursing
研究组 & 干预措施
Irinotecan/Docetaxel
Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m².
Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. This constituted a cycle of treatment. Patients were evaluated after 2 cycles.
干预措施: docetaxel (Drug)
Irinotecan/Docetaxel
Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m².
Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. This constituted a cycle of treatment. Patients were evaluated after 2 cycles.
干预措施: irinotecan hydrochloride (Drug)
Irinotecan/Docetaxel/Cetuximab
Patients received Cetuximab intravenously once a week for 6 weeks. On day 1 of cycle 1 only, an initial dose of 400 mg/m² (over 120 minutes) was administered. Thereafter, a once-a-week maintenance dose of 250 mg/m² (infused over 60 minutes), was given. The infusion rate never exceeded 5 ml/minute.
On the day of the initial dose, the administration of Cetuximab was followed by the administration of docetaxel, after a 60-minute observation period. (The observation period was 30 minutes following maintenance doses.) Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m².
Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. Cetuximab was administered once a week for 6 consecutive weeks. A cycle of treatment was 6 weeks.
干预措施: cetuximab (Biological)
Irinotecan/Docetaxel/Cetuximab
Patients received Cetuximab intravenously once a week for 6 weeks. On day 1 of cycle 1 only, an initial dose of 400 mg/m² (over 120 minutes) was administered. Thereafter, a once-a-week maintenance dose of 250 mg/m² (infused over 60 minutes), was given. The infusion rate never exceeded 5 ml/minute.
On the day of the initial dose, the administration of Cetuximab was followed by the administration of docetaxel, after a 60-minute observation period. (The observation period was 30 minutes following maintenance doses.) Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m².
Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. Cetuximab was administered once a week for 6 consecutive weeks. A cycle of treatment was 6 weeks.
干预措施: docetaxel (Drug)
Irinotecan/Docetaxel/Cetuximab
Patients received Cetuximab intravenously once a week for 6 weeks. On day 1 of cycle 1 only, an initial dose of 400 mg/m² (over 120 minutes) was administered. Thereafter, a once-a-week maintenance dose of 250 mg/m² (infused over 60 minutes), was given. The infusion rate never exceeded 5 ml/minute.
On the day of the initial dose, the administration of Cetuximab was followed by the administration of docetaxel, after a 60-minute observation period. (The observation period was 30 minutes following maintenance doses.) Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m².
Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. Cetuximab was administered once a week for 6 consecutive weeks. A cycle of treatment was 6 weeks.
干预措施: irinotecan hydrochloride (Drug)
结局指标
主要结局
Proportion of Patients With Objective Response Evaluated by RECIST (Solid Tumor Response Criteria)
时间窗: Assessed every 12 weeks until progression
Per RECIST criteria, Complete response (CR)= disappearance of all target and nontarget lesions Partial response (PR)= \>=30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits. Objective response = CR + PR
次要结局
- Progression-free Survival(Assessed every 3 months for 2 years and then every 6 months for 1 year)
- Overall Survival(Assessed every 3 months for 2 years and then every 6 months for 1 year)
- Epidermal Growth Factor Receptor (EGFR) Status(Original tumor tissue samples submitted within one month of patient randomization)
- Proportion of Patients With Thromboembolic Events(Assessed every 6 weeks while on treatment and for 30 days after the end of treatment)