A Randomized, Multicenter, Phase II Open-label Study of the Efficacy and Safety of Pyrotinib + Vinorelbine vs. Treatment of Physician's Choice in Patients With HER2-Positive Locally Advanced or Metastatic Breast Cancer Who Have Received Prior Trastuzumab-Based Therapy
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 256
- 主要终点
- maximum-tolerated dose (MTD)
研究概览
简要总结
The purpose of this study is to identify the highest tolerable dose of pyrotinib in combination with vinorelbine and to assess the safety and efficacy of the combination in Patients With HER2-Positive Locally Advanced or Metastatic Breast Cancer.
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 pyrotinib and vinorelbine in patients with advanced solid tumors. In the second part of the study, we will compare the safety and efficacy of Pyrotinib + vinorelbine vs. Treatment of Physician's Choice in Patients With HER2-Positive Locally Advanced or Metastatic Breast Cancer Who Have Received Prior Trastuzumab-Based Therapy.Participants will be treated until disease progression (PD), unmanageable toxicity, or study termination.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •HER2 status must be prospectively, centrally tested and be HER2-positive based on central laboratory assay results
- •Histologically or cytologically confirmed invasive breast cancer
- •Prior treatment for breast cancer in the adjuvant, unresectable, locally advanced, or metastatic setting must include both a taxane, alone or in combination with another agent, and trastuzumab, alone or in combination with another agent
- •Documented progression (which occur during or after most recent treatment or within 6 months after completing of adjuvant therapy) of incurable, unresectable, locally advanced or metastatic breast cancer, defined by the investigator
- •Measurable and/or nonmeasurable disease; participants with central nervous system-only disease are excluded
- •Cardiac ejection fraction greater than or equal to (>/=) 50 percent (%) by either echocardiogram or multi-gated acquisition scan
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
排除标准
- •History of treatment with pyrotinib
- •Prior treatment with lapatinib or neratinib
- •History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma
- •History of receiving any anti-cancer drug/biologic or investigational treatment within 28 days prior to randomization except hormone therapy
- •Recovery of treatment-related toxicity consistent with other eligibility criteria
- •History of radiation therapy within 28 days of randomization
- •Brain metastases that are untreated, symptomatic, or require therapy to control symptoms, as well as any history of radiation, surgery, or other therapy, including steroids, to control symptoms from brain metastases within 2 months (60 days) of randomization
- •History of symptomatic congestive heart failure or serious cardiac arrhythmia requiring treatment
- •History of myocardial infarction or unstable angina
- •Current severe, uncontrolled systemic disease (for example, clinically significant cardiovascular, pulmonary, or metabolic disease)
- •Pregnancy or lactation
- •Current known active infection with human immunodeficiency virus (HIV) or hepatitis C virus
- •Presence of conditions that could affect gastrointestinal absorption: Malabsorption syndrome, resection of the small bowel or stomach, and ulcerative colitis
研究组 & 干预措施
pyrotinib 320mg + vinorelbine
pyrotinib 320mg tablets administered daily by mouth, vinorelbine 80 mg/m2 weekly (following a first cycle at 60 mg/m2) administered OV on day 1 and day 8 of 21 day cycle. Treatment lasts for two cycles
干预措施: Pyrotinib (Drug)
pyrotinib 320mg + vinorelbine
pyrotinib 320mg tablets administered daily by mouth, vinorelbine 80 mg/m2 weekly (following a first cycle at 60 mg/m2) administered OV on day 1 and day 8 of 21 day cycle. Treatment lasts for two cycles
干预措施: vinorelbine (Drug)
pyrotinib 400mg + vinorelbine
pyrotinib 400mg tablets administered daily by mouth, vinorelbine 80 mg/m2 weekly (following a first cycle at 60 mg/m2) administered OV on day 1 and day 8 of 21 day cycle. Treatment lasts for two cycles
干预措施: Pyrotinib (Drug)
pyrotinib 400mg + vinorelbine
pyrotinib 400mg tablets administered daily by mouth, vinorelbine 80 mg/m2 weekly (following a first cycle at 60 mg/m2) administered OV on day 1 and day 8 of 21 day cycle. Treatment lasts for two cycles
干预措施: vinorelbine (Drug)
Pyrotinib + vinorelbine
pyrotinib administered daily by mouth（MTD）, vinorelbine 80 mg/m2 weekly (following a first cycle at 60 mg/m2) administered OV on day 1 and day 8 of 21 day cycle. Treatments will lasts until disease progression (as assessed by the investigator) or unmanageable toxicity.
干预措施: Pyrotinib (Drug)
Pyrotinib + vinorelbine
pyrotinib administered daily by mouth（MTD）, vinorelbine 80 mg/m2 weekly (following a first cycle at 60 mg/m2) administered OV on day 1 and day 8 of 21 day cycle. Treatments will lasts until disease progression (as assessed by the investigator) or unmanageable toxicity.
干预措施: vinorelbine (Drug)
Treatment of physician's choice
Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity. The treatments included single-agent chemotherapy, single-agent or dual-agent hormonal therapy for hormone receptor positive-disease, and single-agent HER2-directed therapy.
干预措施: Treatment of physician's choice (Drug)
结局指标
主要结局
maximum-tolerated dose (MTD)
时间窗: 42 days
The maximum-tolerated dose (MTD) will be defined as the maximum dose level at which no more than one subject out of three experiences has a dose-limiting toxicity (DLT) upon completing two treatment cycle.
PFS as Assessed by the Investigator
时间窗: From enrollment to progression or death (for any reason),assessed up to 100 months
progression-free survival
次要结局
- Objective Response Rate(from enrollment to progression or death (for any reason), assessed up to 100 months)
- OS(from enrollment to death (for any reason).assessed up to 100 months)
研究者
wang shusen
clinical professor
Sun Yat-sen University