A Randomized Phase II Study of Bevacizumab in Combination With Cetuximab Plus Irinotecan, or in Combination With Cetuximab Alone, in Irinotecan-Refractory Colorectal Cancer

National Cancer Institute (NCI)1 个研究点分布在 1 个国家目标入组 70 人开始时间: 2003年12月最近更新: 2015年4月15日

适应症

干预措施

试验速览

阶段: 2 期
状态: 已完成
发起方: National Cancer Institute (NCI)
入组人数: 70
试验地点: 1
主要终点: Time to tumor progression

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This randomized phase II trial is studying giving bevacizumab and cetuximab together with irinotecan to see how well it works compared to giving bevacizumab and cetuximab alone in treating patients with irinotecan-refractory metastatic colorectal cancer. Monoclonal antibodies such as cetuximab and bevacizumab can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or deliver tumor -killing substances to them. Drugs used in chemotherapy, such as irinotecan, also work in different ways to kill tumor cells or stop them from growing. Giving cetuximab and bevacizumab together with irinotecan may improve the ability to block tumor growth.

详细描述

PRIMARY OBJECTIVES:

I. Evaluate time to tumor progression in patients with irinotecan-refractory metastatic colorectal cancer treated with bevacizumab and cetuximab with or without irinotecan.

II. Evaluate objective response rate in patients treated with these regimens. III. Evaluate overall survival of patients treated with these regimens. IV. Evaluate safety, tolerability, and adverse event profiles of these regimens in these patients.

V. Correlate a panel of molecular markers (e.g., those involved in the epidermal growth factor receptor signaling pathway, angiogenic pathway, and irinotecan metabolism) with clinical outcome in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, ECOG performance status (0 vs 1), and albumin (> 3.0 g/dL vs ≤ 3.0 g/dL). Patients are randomized to 1 of 2 treatment arms.

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 or cytologically confirmed colorectal cancer
•Metastatic disease by diagnostic imaging studies
•Measurable disease
•At least 1 unidimensionally measurable lesion with minimum lesion size at least twice the slice thickness of the imaging study used
•Refractory to irinotecan, evidenced by clinical documentation
•Received at least 1 prior irinotecan-containing chemotherapy regimen for metastatic disease and progressed during or within 6 weeks after completion of therapy
•Must have received prior irinotecan according to 1 of the following schedules:
•Weekly administration with a starting dose of 100-125 mg/m^2
•Biweekly administration (every other week) with a starting dose of approximately 180 mg/m^2
•Once every three weekly administration with a starting dose of 300-350 mg/m^2
•No known brain metastases
•No prior primary CNS tumors
•Performance status - ECOG 0-1
•Performance status - Karnofsky 80-100%
•More than 3 months
•WBC >= 3,000/mm^3
•Absolute neutrophil count >= 1,500/mm^3
•Platelet count >= 100,000/mm^3
•Hemoglobin >= 9 g/dL
•No bleeding diathesis or coagulopathy
•Bilirubin normal
•AST and ALT =< 2.5 times upper limit of normal (ULN) (5 times ULN in the presence of known liver metastases)
•INR < 1.5 (for patients receiving warfarin)
•Creatinine =< ULN
•Creatinine clearance ≥ 60 mL/min
•No proteinuria
•No prior stroke
•No symptomatic congestive heart failure
•No unstable angina pectoris
•No uncontrolled hypertension
•No clinically significant cardiac arrhythmia
•None of the following arterial thromboembolic events within the past 6 months:
•Myocardial infarction
•Cerebrovascular accident
•Transient ischemic attack
•Unstable angina
•Not pregnant or nursing
•Negative pregnancy test
•Fertile patients must use effective contraception during and for at least 3 months after study participation
•No significant traumatic injury within the past 28 days
•No grade 3 or greater neurotoxicity
•No uncontrolled seizures
•No prior allergic reactions attributed to compounds of similar chemical or biological composition to study agents
•No prior irinotecan intolerance
•No ongoing or active infection requiring parenteral antibiotics
•No serious nonhealing active wound, ulcer, or bone fracture
•No psychiatric illness or social situation that would preclude study compliance
•No other concurrent uncontrolled illness that would preclude study participation
•No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
•No prior cetuximab
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排除标准

未提供

研究组 & 干预措施

Arm A (cetuximab, bevacizumab, irinotecan)I

Experimental

Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 36; bevacizumab IV over 30-90 minutes on days 1*, 15, and 29 OR on days 1 and 22; and irinotecan IV over 30-90 minutes (at the same dose and schedule that the patient previously received) beginning on day 1.