A Phase 1/2 Study of HKI-272 in Combination With Paclitaxel in Subjects With Solid Tumors and Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 110
- 试验地点
- 32
- 主要终点
- Maximum Tolerated Dose
研究概览
简要总结
The purpose of this study is to learn whether it is safe and effective to administer HKI-272 (neratinib) in combination with paclitaxel in patients with breast cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Inclusion criteria for both parts of clinical trial:
- •Good performance status
- •Normal ejection fraction
- •Adequate cardiac, kidney, and liver function
- •Adequate blood counts
- •At least one measurable target lesion
- •Negative pregnancy test for female subjects
- •Inclusion Criteria for Part 1 Only:
- •Pathologically confirmed solid tumor not curable with available standard therapy
- •Inclusion Criteria for Part 2 Only:
- •Pathologically confirmed breast cancer
- •HER2 positive tumor
- •Prior treatment with Herceptin
排除标准
- •Exclusion criteria for both parts of clinical trial:
- •Major surgery, radiotherapy, chemotherapy or investigational agents within two weeks of treatment day 1
- •Subjects with bone or skin as the only site of disease
- •Active central nervous system metastases
- •Significant cardiac disease or dysfunction
- •Significant gastrointestinal disorder
- •Inability or unwillingness to swallow HKI-272 capsules
- •Prior exposure to HKI-272 or other HER2 targeted agents, except trastuzumab (Part 2 only). Prior lapatinib is permitted in arm B of part
- •Treatment with a taxane within 3 months of treatment day 1
- •Grade 2 or greater motor or sensory neuropathy
- •Pregnant or breast feeding women
- •Known hypersensitivity to paclitaxel or Cremophor EL
- •Prior treatment with anthracyclines with cumulative dose of >400 mg/m^2
- •Any other cancer within 5 years with the exception of contralateral breast cancer, adequately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin
- •Exclusion Criteria for Part 2 Only:
- •More than 1 (arm A) or 3 (arm B) prior cytotoxic chemotherapy regimen for metastatic disease
研究组 & 干预措施
HKI-272 dose level 1
Part 1: Subjects with solid tumors receiving HKI-272 (neratinib) 160 mg daily by mouth in combination with paclitaxel 80 mg/m^2 weekly IV.
干预措施: HKI-272 (Drug)
HKI-272 dose level 1
Part 1: Subjects with solid tumors receiving HKI-272 (neratinib) 160 mg daily by mouth in combination with paclitaxel 80 mg/m^2 weekly IV.
干预措施: Paclitaxel (Drug)
HKI-272 dose level 2
Part 1: Subjects with solid tumors receiving HKI-272 (neratinib) 240 mg daily by mouth in combination with paclitaxel 80 mg/m^2 weekly IV.
干预措施: HKI-272 (Drug)
HKI-272 dose level 2
Part 1: Subjects with solid tumors receiving HKI-272 (neratinib) 240 mg daily by mouth in combination with paclitaxel 80 mg/m^2 weekly IV.
干预措施: Paclitaxel (Drug)
HKI-272 expanded MTD cohort, arm A
Part 2: Subjects with metastatic breast cancer who have not received more than 1 prior cytotoxic chemotherapy treatment regimen for metastatic disease receiving HKI-272 (neratinib) 240 mg daily by mouth in combination with paclitaxel 80 mg/m^2 weekly IV.
干预措施: HKI-272 (Drug)
HKI-272 expanded MTD cohort, arm A
Part 2: Subjects with metastatic breast cancer who have not received more than 1 prior cytotoxic chemotherapy treatment regimen for metastatic disease receiving HKI-272 (neratinib) 240 mg daily by mouth in combination with paclitaxel 80 mg/m^2 weekly IV.
干预措施: Paclitaxel (Drug)
HKI-272 expanded MTD cohort, arm B
Part 2: Subjects with metastatic breast cancer who have not received more than 3 prior cytotoxic chemotherapy treatment regimen for metastatic disease receiving HKI-272 (neratinib) 240 mg daily by mouth in combination with paclitaxel 80 mg/m^2 weekly IV.
干预措施: HKI-272 (Drug)
HKI-272 expanded MTD cohort, arm B
Part 2: Subjects with metastatic breast cancer who have not received more than 3 prior cytotoxic chemotherapy treatment regimen for metastatic disease receiving HKI-272 (neratinib) 240 mg daily by mouth in combination with paclitaxel 80 mg/m^2 weekly IV.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Maximum Tolerated Dose
时间窗: From first dose date through day 28.
Maximum Tolerated Dose (MTD) of neratinib, daily, in combination with paclitaxel 80 mg/m², intravenous at days 1, 8, and 15, associated with the dose limiting toxicity data.
Objective Response Rate
时间窗: From first dose date to progression or last tumor assessment, up to 140 weeks
Subjects with partial response (PR) or complete response (CR) with ERBB2 positive breast cancer treated at the maximum tolerated dose (MTD) of neratinib in combination with paclitaxel, per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.0: CR, disappearance of all target lesions; PR, \>=30% decrease in the sum of the longest diameter of target lesions; and no progressive disease (PD) for non-target lesions, and no new lesions.
Dose Limiting Toxicity Incidence of Neratinib in Combination With Paclitaxel
时间窗: From first dose date through day 28
Dose Limiting Toxicity in subjects with solid tumors treated with neratinib, administered daily, in combination with paclitaxel 80 mg/m² IV on days 1, 8, and 15 of a 28 day cycle.
次要结局
- Area Under the Concentration-time Curve 0-24(Samples taken at 0 hour and at 1, 2, 4, 6, 8, and 24 hours postdose on Day 15 of Cycle 1, and 1 predose sample on Day 1 in Cycle 1.)
- Maximum Plasma Concentration of Neratinib(Samples taken at 0 hour and at 1, 2, 4, 6, 8, and 24 hours postdose on Day 15 of Cycle 1, and 1 predose sample on Day 1 in Cycle 1.)