An Ascending Single and Multiple Dose Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of HKI-272 Administered Orally to Subjects With HER-2/NEU or HER-1/EGFR-Positive Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 73
- 试验地点
- 5
- 主要终点
- Dose Limiting Toxicity (DLT)
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability as well as find the maximum tolerated dose (MTD) for HKI-272. In addition, this study will examine the effects of the study drug on your tumor, and how your body uses and eliminates HKI-272.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Her2/neu or Her1/EGFR positive cancer
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- •Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
排除标准
- •Prior treatment with anthracyclines with a cumulative dose of doxorubicin or equivalent of greater than 300 mg/m^2
- •Patients with significant cardiac risk factors
- •Active central nervous system metastasis
研究组 & 干预措施
Neratinib 40 mg
干预措施: neratinib (Drug)
Neratinib 80 mg
干预措施: neratinib (Drug)
Neratinib 120 mg
干预措施: neratinib (Drug)
Neratinib 180 mg
干预措施: neratinib (Drug)
Neratinib 240 mg
干预措施: neratinib (Drug)
Neratinib 320 mg
干预措施: neratinib (Drug)
Neratinib 400 mg
干预措施: neratinib (Drug)
Neratinib 320 mg MTD
干预措施: neratinib (Drug)
结局指标
主要结局
Dose Limiting Toxicity (DLT)
时间窗: From first dose date to day 14
DLT is defined as any neratinib-related nonhematologic grade 3 or any grade 4 adverse event (AE) according to the National Cancer Institute (NCI) common terminology criteria (CTC) for AEs version 3.0. DLTs were assessed from the first single dose to 14 days of continuous daily administration.
Maximum Tolerated Dose (MTD)
时间窗: From first dose date to day 14
If 2 or more, of 3 to 6 subjects, at a dose level had an neratinib-related dose limiting toxicity (DLT) by day 14 of continuous daily dose administration, dose escalation stopped and the prior dose level was considered the MTD.
次要结局
- Number of Participants With Best Overall Response(From first dose date to progression or last tumor assessment, up to 39 weeks.)
- Duration of Response(From start date of response to first PD, up to 39 weeks.)
- Progression Free Survival(From first dose date to progression or death, up to 39 weeks.)
- Objective Response Rate(From first dose date to progression/death or last assessment, up to 39 weeks)
- Clinical Benefit Rate(From first dose date to progression/death or last assessment, up to 39 weeks.)