A Phase 1/2 Study Of HKI-272 In Combination With Vinorelbine In Subjects With Solid Tumors And Metastatic Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 92
- 试验地点
- 35
- 主要终点
- Maximum Tolerated Dose
研究概览
简要总结
The purpose of this study is to identify the highest tolerable dose of neratinib (HKI-272) in combination with vinorelbine and to assess the safety of the combination of the two drugs as well as to obtain preliminary information on whether the combination of the two drugs has any effect on solid tumors.
The study will be conducted in two parts. In the first part, testing will be done on up to 12 subjects to determine the highest tolerable dose of HKI-272 and vinorelbine in patients with advanced solid tumors. In the second part of the study, approximately 60 additional subjects with metastatic ErbB-2-positive breast cancer, with no prior exposure to lapatinib, are planned to be added to better define the tolerability and preliminary activity of HKI-272 in combination with vinorelbine. Up to 20 additional subjects with ErbB-2-positive breast cancer with prior lapatinib exposure are also planned to be enrolled in part 2 for exploratory analyses.
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
- •Confirmed pathologic diagnosis of a solid tumor that is not curable with available therapies for which HKI-272 plus vinorelbine is a reasonable treatment option (part 1 only) or Confirmed pathologic diagnosis of ErbB-2-positive breast cancer (current stage IV) in female subjects for which vinorelbine plus HKI-272 is a reasonable treatment option (part 2 only).
- •At least 1 prior antineoplastic chemotherapy treatment regimen for metastatic disease and at least 1 prior treatment with a trastuzumab-containing regimen for at least 6 weeks, for metastatic disease or subject relapsing under adjuvant treatment (part 2 only).
- •At least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST).
排除标准
- •More than 2 prior antineoplastic treatment regimens (excluding hormonotherapy) for metastatic disease. Subjects who relapsed under adjuvant treatment shouldn't have received more than one line of chemotherapy for metastatic disease (part 2 only).
- •Prior treatment with vinorelbine for metastatic setting, or prior treatment with any ErbB-2 targeted agents except trastuzumab (part 2 only). Up to 20 subjects with ErbB-2-overexpressing metastatic breast cancer who have been previously exposed to lapatinib but are not refractory to lapatinib may be enrolled in part
- •Prior treatment with anthracyclines with a cumulative dose of doxorubicin of greater than 400 mg/m2, or of epirubicin dose of greater than 800 mg/m2, or the equivalent dose for other anthracyclines or derivatives (part 2 only).
研究组 & 干预措施
neratinib 160 mg + vinorelbine
neratinib 160 mg tablets administered daily by mouth, vinorelbine 25 mg/m^2 administered IV on day 1 and day 8 of 21 day cycle
干预措施: neratinib (Drug)
neratinib 160 mg + vinorelbine
neratinib 160 mg tablets administered daily by mouth, vinorelbine 25 mg/m^2 administered IV on day 1 and day 8 of 21 day cycle
干预措施: vinorelbine (Drug)
neratinib 240 mg + vinorelbine
neratinib 240 mg tablets administered daily by mouth, vinorelbine 25 mg/m^2 administered IV on day 1 and day 8 of 21 day cycle
干预措施: neratinib (Drug)
neratinib 240 mg + vinorelbine
neratinib 240 mg tablets administered daily by mouth, vinorelbine 25 mg/m^2 administered IV on day 1 and day 8 of 21 day cycle
干预措施: vinorelbine (Drug)
neratinib 240 mg + vinorelbine, No Prior Lapatinib
neratinib 240 mg tablets administered daily by mouth, vinorelbine 25 mg/m^2 administered IV on day 1 and day 8 of 21 day cycle
干预措施: neratinib (Drug)
neratinib 240 mg + vinorelbine, No Prior Lapatinib
neratinib 240 mg tablets administered daily by mouth, vinorelbine 25 mg/m^2 administered IV on day 1 and day 8 of 21 day cycle
干预措施: vinorelbine (Drug)
neratinib 240 mg + vinorelbine, Prior Lapatinib
neratinib 240 mg tablets administered daily by mouth, vinorelbine 25 mg/m^2 administered IV on day 1 and day 8 of 21 day cycle
干预措施: neratinib (Drug)
neratinib 240 mg + vinorelbine, Prior Lapatinib
neratinib 240 mg tablets administered daily by mouth, vinorelbine 25 mg/m^2 administered IV on day 1 and day 8 of 21 day cycle
干预措施: vinorelbine (Drug)
结局指标
主要结局
Maximum Tolerated Dose
时间窗: From Day 1 to Day 21.
Maximum Tolerated Dose (MTD) of Neratinib in combination with vinorelbine in subjects with advanced solid tumors.
Overall Response Rate
时间窗: From first dose date to progression or last tumor assessment, up to four years and six months.
Overall Response Rate (ORR), subjects with CR or PR by independent review in subjects with ErbB-2-positive breast cancer treated at the MTD of neratinib in combination with vinorelbine per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions.
次要结局
- Progression-Free Survival(From first dose date to progression or death, up to four years and six months.)
- Clinical Benefit Rate(From first dose date to progression or last tumor assessment, up to four years and six months.)
- Duration Of Response(From start date of response to first PD/death, up to four years and six months.)