Phase I Study of Bortezomib (Velcade) and Cetuximab (Erbitux) for Patients With Solid Tumors Expressing EGFR
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose (MTD) of bortezomib
研究概览
简要总结
RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab, 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 carry tumor-killing substances to them. Giving bortezomib together with cetuximab may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given together with cetuximab in treating patients with advanced solid tumors.
详细描述
OBJECTIVES:
Primary
- To determine the maximum tolerated dose of bortezomib when given together with cetuximab in patients with advanced solid tumors expressing epidermal growth factor receptor (EGFR).
Secondary
- To obtain preliminary information about the anti-tumor activity of bortezomib and cetuximab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Diagnosis of solid tumor that overexpresses epidermal growth factor receptor (EGFR) including, but not limited to, the following:
- •Breast cancer
- •Lung cancer
- •Colon cancer
- •Pancreatic cancer
- •Head and neck cancer
- •Kidney cancer
- •Advanced disease
- •Must have failed or become intolerant to prior standard therapy and is no longer likely to respond to such therapy
- •Measurable or nonmeasurable disease
- •ECOG performance status 0-1
- •ANC ≥ 1,500/mm³
- •Platelet count > 100,000/mm³
- •Hemoglobin > 9 g/dL
- •Bilirubin < 1.5 times upper limit of normal (ULN)
- •Alkaline phosphatase < 3.0 times ULN (5.0 times ULN if liver has tumor involvement)
- •Aspartate aminotransferase (AST) and alanine aminotransferase (*ALT) < 3.0 times upper limit of normal (ULN) (5.0 times ULN if liver has tumor involvement)
- •Creatinine clearance > 30 mL/min
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for 3 months after completion of study treatment
- •Recovered from all prior therapy
- •Prior systemic chemotherapy, immunotherapy, or biological therapy allowed
- •At least 14 days since prior radiotherapy or systemic therapy
- •At least 30 days since prior investigational agents
- •At least 14 days since other prior investigational drugs (for reasons other than the treatment of cancer)
排除标准
- •Untreated or symptomatic central nervous system (CNS) metastases
- •Concurrent serious systemic disorders (e.g., active infection) that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study
- •Uncontrolled diabetes
- •Myocardial infarction within the past 6 months
- •New York Heart Association (NYHA) class III or IV heart failure
- •Uncontrolled angina
- •Severe uncontrolled ventricular arrhythmias
- •Evidence of acute ischemia or active conduction system abnormalities by ECG
- •Peripheral neuropathy Common Terminology Criteria for Adverse Events (CTCAE) grade > 2
- •Known hypersensitivity to bortezomib, boron, or mannitol
- •Serious medical or psychiatric illness likely to interfere with study participation
- •Prior bortezomib and/or cetuximab
- •Concurrent filgrastim (G-CSF) or other hematologic support during course 1 of study treatment
研究组 & 干预措施
Bortezomib and Cetuximab
The starting dose of bortezomib will be 1.3 mg/m2 with a 0.1 increment increase with each successive dose level to a maximum of 2.0 mg/m2. A loading dose of cetuximab will be given on day 1 (400 mg/m2) followed by a weekly dose of 250 mg/m2.
干预措施: cetuximab (Biological)
Bortezomib and Cetuximab
The starting dose of bortezomib will be 1.3 mg/m2 with a 0.1 increment increase with each successive dose level to a maximum of 2.0 mg/m2. A loading dose of cetuximab will be given on day 1 (400 mg/m2) followed by a weekly dose of 250 mg/m2.
干预措施: bortezomib (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD) of bortezomib
时间窗: At end of Cycle 1 (Week 3)
The standard Phase I design will be used to determine the maximum tolerated dose of bortezomib when given with weekly cetuximab. The MTD is defined as the highest dose studied for which the incidence of dose limiting toxicity (DLT) was less than 33%.
次要结局
- Disease response as measured by RECIST criteria(At Week 4)