Phase I Study To Determine The Safety, Tolerance And Preliminary Antineoplastic Activity Of Combined EGFR (erbB1) And HER2 (erbB2) Blockade, With OSI-774 And Trastuzumab, In Combination With Weekly Paclitaxel
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Maximally tolerated dose (MTD), graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
研究概览
简要总结
Phase I trial to study the effectiveness of combining erlotinib and trastuzumab with paclitaxel in treating patients who have advanced solid tumors. Biological therapies such as erlotinib may interfere with the growth of the tumor cells and slow the growth of the tumor. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining erlotinib and trastuzumab with paclitaxel may kill more tumor cells
详细描述
OBJECTIVES:
I. Determine the safety, quantitative and qualitative toxic effects, maximum tolerated dose, and dose-limiting toxic effects of erlotinib when combined with paclitaxel and trastuzumab (Herceptin) in patients with advanced solid tumors.
II. Determine the relevant pharmacokinetic interactions between these agents in these patients.
III. Determine, preliminarily, the antitumor activity of this regimen in these patients.
OUTLINE: This is an open-label, non-randomized, multicenter, dose-escalation study of erlotinib.
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
- •Histologically confirmed metastatic solid tumor for which there are no effective standard treatment options
- •HER2 positive (1+ to 3+)
- •Tumor has a high likelihood of expressing epidermal growth factor receptor (EGFR)
- •No evidence of leptomeningeal disease or brain metastases unless previously treated, currently asymptomatic, and off both antiepileptics and dexamethasone
- •Patients with treated brain metastases are eligible if they are without any clinical change in their brain disease status for at least 4 weeks after whole brain irradiation
- •Performance status - ECOG 0-2
- •Performance status - Karnofsky 60-100%
- •At least 12 weeks
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •Bilirubin normal
- •AST/ALT no greater than 2.5 times upper limit of normal (ULN) (5 times ULN if liver has tumor involvement)
- •Creatinine normal
- •Creatinine clearance at least 60 mL/min
- •LVEF more than 50% by radionuclide ventriculogram or MUGA scan
- •No significant cardiovascular disease
- •No prior congestive heart failure requiring therapy
- •No unstable angina pectoris
- •No myocardial infarction within the past 6 months
- •No gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation
- •Patients who are unable to swallow tablets and/or who have silicon-based G-tubes may dissolve the tablets in distilled water
- •No active peptic ulcer disease
- •HIV negative
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No known or suspected hypersensitivity to paclitaxel
- •No prior allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib or other study agents
- •No concurrent active infection
- •No other concurrent medical condition that would preclude study participation
- •No persistent grade 2 or greater neurotoxicity/neuropathy from any cause
- •No psychiatric disorders or altered mental status that would preclude study participation
- •No other concurrent immunotherapy
- •No concurrent cytokine growth factors (e.g., colony-stimulating factors)
- •At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered
- •No other concurrent chemotherapy
- •See Disease Characteristics
- •No concurrent hormonal therapy except megestrol as an appetite stimulant or luteinizing hormone-releasing hormone agonists for prostate cancer
- •See Disease Characteristics
- •No concurrent radiotherapy
- •No prior surgical procedures affecting absorption
- •No prior EGFR-targeting therapy
- •No other concurrent experimental medications or other specific antitumor therapy
- •No concurrent immunosuppressant therapy
- •No concurrent antiarrhythmic therapy for a ventricular arrhythmia
排除标准
- 未提供
研究组 & 干预措施
Treatment (paclitaxel, trastuzumab, erlotinib hydrochloride)
See detailed description.
干预措施: paclitaxel (Drug)
Treatment (paclitaxel, trastuzumab, erlotinib hydrochloride)
See detailed description.
干预措施: trastuzumab (Biological)
Treatment (paclitaxel, trastuzumab, erlotinib hydrochloride)
See detailed description.
干预措施: erlotinib hydrochloride (Drug)
Treatment (paclitaxel, trastuzumab, erlotinib hydrochloride)
See detailed description.
干预措施: laboratory biomarker analysis (Other)
Treatment (paclitaxel, trastuzumab, erlotinib hydrochloride)
See detailed description.
干预措施: pharmacological study (Other)
结局指标
主要结局
Maximally tolerated dose (MTD), graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
时间窗: Up to day 28
Response rates, as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)
时间窗: Up to 6 years
次要结局
- Incidence of adverse events, graded according to the NCI CTC v2.0(Up to 30 days after last study treatment)