A Phase 1/2, Open-Label Study Of Neratinib (HKI-272) In Combination With Capecitabine In Subjects With Solid Tumors And ErbB-2 Positive Metastatic Or Locally Advanced Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 105
- 试验地点
- 37
- 主要终点
- Number of Participants With Dose Limiting Toxicities
研究概览
简要总结
This is a world wide phase 1/2, open-label, study of neratinib in combination with capecitabine, conducted in 2 parts.
In Part 1, 3 to 9 subjects with solid tumors will be enrolled in each dose group of the combination of neratinib and capecitabine. Each subject will participate in only 1 dose group.
Additional subjects may be included at any dose level to further assess the safety and tolerability at that dose level.
In Part 2, up to 60 subjects with erbB-2 positive metastatic breast cancer will receive treatment with the combination of neratinib and capecitabine at the maximum tolerated dose level, as determined in Part 1. In addition 20 subjects with prior lapatinib exposure will be enrolled in Part 2.
Depending on the safety and activity profile observed during the dose escalation phase, the dose selected for Part 2 may be adjusted, if appropriate. In case one test article of the combination is discontinued due to intolerance the other test article can be administered alone.
The primary objectives of Part 1 are to assess the safety and tolerability, and to define the maximum tolerated dose (MTD) of neratinib in combination with capecitabine in subjects with advanced solid tumors.
The primary objective of Part 2 of this study is to confirm the MTD determined in Part 1.
The secondary objective of Part 1 is to collect information on preliminary anti-tumor activity of the combination of neratinib and capecitabine.
Secondary objectives for Part 2 are to collect pharmacokinetic information and to obtain additional efficacy data, such as Objective Response Rate, for subjects with erbB-2 positive breast cancer treated at the MTD of neratinib + capecitabine.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Neratinib and Capecitabine (Dose Level 1)
Neratinib 160 mg and Capecitabine 1500 mg/m^2
干预措施: Neratinib (Drug)
Neratinib and Capecitabine (Dose Level 1)
Neratinib 160 mg and Capecitabine 1500 mg/m^2
干预措施: Capecitabine (Drug)
Neratinib and Capecitabine (Dose Group 2)
Neratinib 240 mg and Capecitabine 1500 mg/m^2
干预措施: Neratinib (Drug)
Neratinib and Capecitabine (Dose Group 2)
Neratinib 240 mg and Capecitabine 1500 mg/m^2
干预措施: Capecitabine (Drug)
Neratinib and Capecitabine (Dose Group 3)
Neratinib 240 mg and Capecitabine 2000 mg/m^2
干预措施: Neratinib (Drug)
Neratinib and Capecitabine (Dose Group 3)
Neratinib 240 mg and Capecitabine 2000 mg/m^2
干预措施: Capecitabine (Drug)
Neratinib and Capecitabine (Dose Group 4)
Neratinib 200 mg and Capecitabine 2000 mg/m^2
干预措施: Neratinib (Drug)
Neratinib and Capecitabine (Dose Group 4)
Neratinib 200 mg and Capecitabine 2000 mg/m^2
干预措施: Capecitabine (Drug)
Neratinib and Capecitabine (Dose Group 5)
Neratinib 160 mg and Capecitabine 2000 mg/m^2
干预措施: Neratinib (Drug)
Neratinib and Capecitabine (Dose Group 5)
Neratinib 160 mg and Capecitabine 2000 mg/m^2
干预措施: Capecitabine (Drug)
Neratinib and Capecitabine MTD (Dose Group 6)
Neratinib and Capecitabine Maximum Tolerated Dose without prior lapatinib
干预措施: Neratinib (Drug)
Neratinib and Capecitabine MTD (Dose Group 6)
Neratinib and Capecitabine Maximum Tolerated Dose without prior lapatinib
干预措施: Capecitabine (Drug)
Neratinib and Capecitabine MTD (Dose Group 7)
Neratinib and Capecitabine Maximum Tolerated Dose with prior lapatinib
干预措施: Neratinib (Drug)
Neratinib and Capecitabine MTD (Dose Group 7)
Neratinib and Capecitabine Maximum Tolerated Dose with prior lapatinib
干预措施: Capecitabine (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities
时间窗: From first dose date to day 21
Number of participants reporting Adverse Events Causing Dose Limiting Toxicities (DLT).
Maximum Tolerated Dose (MTD) of Capecitabine
时间窗: From first dose date to day 21.
MTD reflects the highest dose of capecitabine in combination with neratinib that did not cause a selected Grade 3 toxicity in \>= 2 participants, which is any of 1) Grade 3 or 4 non-hematologic toxicity (Grade 3 asthenia was not considered a DLT unless lasting \>3 days, 2) Grade 3 diarrhea lasting \>2 days on optimal medical therapy or associated with fever or dehydration. 3) Grade 4 neutropenia lasting ≥ 3 days or Grade 4 febrile neutropenia, 4) Grade 4 thrombocytopenia lasting ≥3 days or associated with bleeding or requiring platelet transfusion, 5) Delayed recovery \[to ≥ National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or baseline\] from one of the above listed toxicities that were related to neratinib and/or capecitabine that delayed the initiation of the next dose by more than 3 weeks.
Maximum Tolerated Dose (MTD) of Neratinib
时间窗: From first dose date to day 21.
MTD reflects the highest dose of neratinib plus capeciteabine that did not cause a selected Grade 3 toxicity in \>= 2 participants, which is any of 1) Grade 3 or 4 non-hematologic toxicity (Grade 3 asthenia was not considered a DLT unless lasting \>3 days, 2) Grade 3 diarrhea lasting \>2 days on optimal medical therapy or associated with fever or dehydration. 3) Grade 4 neutropenia lasting ≥ 3 days or Grade 4 febrile neutropenia, 4) Grade 4 thrombocytopenia lasting ≥3 days or associated with bleeding or requiring platelet transfusion, 5) Delayed recovery \[to ≥ National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or baseline\] from one of the above listed toxicities that were related to neratinib and/or capecitabine that delayed the initiation of the next dose by more than 3 weeks.
次要结局
- Overall Response Rate(From first dose date to progression or last tumor assessment, up to three years.)
- Clinical Benefit Rate(From first dose date to progression or last tumor assessment, up to three years.)
- Duration of Response(From start date of response to first PD/death, up to three years.)