A Phase I/II Study of HKI-272 in Combination With Trastuzumab (Herceptin) in Subjects With Advanced Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 13
- 主要终点
- 16-week Progression-free Survival (PFS) Rate
研究概览
简要总结
The purpose of this study is to determine the safety and efficacy of HKI-272 (neratinib) in combination with trastuzumab in patients with advanced breast cancer.
详细描述
Open label phase 1/2 study of ascending multiple oral doses of HKI-272 in combination with IV trastuzumab in subjects with advanced human epidermal growth factor receptor 2 positive (HER2+) breast cancer. Three to six subjects will be enrolled in each dose group. Adverse events and dose limiting toxicities will be assessed from the first dose of study drug though day 21. When the maximum tolerated dose (MTD) of HKI-272 plus trastuzumab is determined, an additional 30 subjects will be enrolled at that dose level, and followed for progression free survival for approximately 1 year.
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
- •Pathologic diagnosis of breast cancer with current stage IIIB, IIIC or IV not curable by available therapy
- •Progression following at least one Herceptin-containing cytotoxic chemotherapy regimen (neoadjuvant, adjuvant, or metastatic setting)
- •HER2 positive breast cancer
- •At least one measurable target lesion
- •Adequate performance status
- •Adequate cardiac, kidney, and liver function
- •Adequate blood counts
- •Willingness of all subjects who are not surgically sterile or post menopausal to use acceptable methods of birth control
排除标准
- •More than 3 prior cytotoxic chemotherapy regimens for locally advanced or metastatic disease
- •Major surgery, chemotherapy, radiotherapy, investigational agents, Herceptin or other cancer therapy within 2 weeks of treatment day 1
- •Prior treatment with anthracyclines with cumulative dose of >400 mg/m^2
- •Extensive visceral disease
- •Active central nervous system metastases
- •Pregnant or breast feeding women
- •Significant chronic or recent acute gastrointestinal disorder with diarrhea as a major symptom
- •Prior exposure to HKI-272 or other HER2 targeted agents (except Herceptin and Tykerb)
- •Significant cardiac disease or dysfunction
- •History of life-threatening hypersensitivity to Herceptin
- •Inability or unwillingness to swallow HKI-272 capsules
- •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
研究组 & 干预措施
Part 1 - dose level 1 (160 mg)
All subjects receiving HKI-272 dose level 1 in combination with trastuzumab
干预措施: HKI-272 (Drug)
Part 1 - dose level 1 (160 mg)
All subjects receiving HKI-272 dose level 1 in combination with trastuzumab
干预措施: trastuzumab (Drug)
Part 1 - dose level 2 (240 mg)
All subjects receiving HKI-272 dose level 2 in combination with trastuzumab
干预措施: HKI-272 (Drug)
Part 1 - dose level 2 (240 mg)
All subjects receiving HKI-272 dose level 2 in combination with trastuzumab
干预措施: trastuzumab (Drug)
Part 2 - expanded MTD cohort
All subjects receiving HKI-272 in combination with trastuzumab
干预措施: HKI-272 (Drug)
Part 2 - expanded MTD cohort
All subjects receiving HKI-272 in combination with trastuzumab
干预措施: trastuzumab (Drug)
结局指标
主要结局
16-week Progression-free Survival (PFS) Rate
时间窗: From first dose date to progression status (PD or death) at 16-week
16-week progression-free survival (PFS) rate for subjects with advanced breast cancer who receive neratinib at the maximum tolerated dose (MTD) in combination with trastuzumab, evaluable population.
次要结局
- Objective Response Rate (ORR)(From first dose date to progression or last tumor assessment, up to five and a half years.)
- Duration of Response (DOR)(From start date of response to first PD, assessed up to five and half years after the first subject was randomized)
- Progression Free Survival (PFS)(From first dose date to progression or death, assessed up to five and half years.)
- Clinical Benefit Rate (CBR)(From first dose date to progression or last tumor assessment, assessed up to five and half years.)
- Area Under the Curve of Neratinib Concentration(Prior to the first dose, and at hours 1, 2, 4, 6, 8 and 24 on days 22.)
- Terminal-phase Elimination Half-life of Neratinib in Combination With Trastuzumab.(Prior to the first dose, on days 22 through 23 of month 1, and on day 1 in months 2 through 6)