A Randomized, Open-label Study of First Line Pyrotinib, Trastuzumab With an Aromatase Inhibitors, in the Treatment of HER2 Positive and HR Positive Metastatic or Inoperable Locally Advanced Breast Cancer
试验速览
- 阶段
- 2 期
- 入组人数
- 250
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
This study is a randomized, open-label, phase II study, comparing the efficacy and safety of trastuzumab plus aromatase inhibitors, with or without pyrotinib, in the treatment of HR (hormone receptor)+/HER2 (human epidermal growth factor receptor 2) + MBC and inoperable LABC patients.
详细描述
This is a randomized, two-arm, open-label, multicenter phase II trial. Our primary purpose is to compare that PFS of patients with trastuzumab, AI plus pyrotinib and trastuzumab plus an AI for HER2-positive and hormone receptor-positive MBC or locally advanced breast cancer (LABC).
Eligible patients will randomized to a ratio of 1:1 to pyrotinib+ trastuzumab + aromatase inhibitor (experimental group) or trastuzumab+aromatase inhibitor (control group). Stratification factors were 1)time since adjuvant hormone therapy (<=12 months/>12 months/no prior hormone therapy); 2) lesion (visceral; non-visceral).
In treatment period, patients will be administrated trastuzumab plus aromatase inhibitors, with or without pyrotinib, every 21 days for 1 cycle, until disease progression, toxicity intolerance, withdrawal of informed consent, patients judged must be terminated study termination.
The imaging evaluation was performed according to the RECIST 1.1 criteria every 6 weeks.
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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Age≥18 years, female;
- •Postmenopausal or pre-menopausal with ovarian function suppression;
- •At least one measurable lesion evaluable according to Response Evaluation Criteria In Solid Tumors Version 1.1;
- •Metastatic or inoperable local advanced breast cancer;
- •HER2-positive breast cancer;
- •HR-positive breast cancer;
排除标准
- •Previous systemic non-hormonal anticancer therapy in the metastatic or advanced breast cancer setting;
- •Received endocrine therapy within 7 days before randomization;
- •Uncontrolled central nervous system metastases;
- •Disease-free interval from completion of adjuvant/neo-adjuvant systemic non-hormonal treatment to recurrence of within 6 months.
- •Other malignancies within the last 3 years, except for carcinoma in situ of the cervix or basal cell carcinoma.
- •Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during the course of study treatment
- •Severe organ dysfunction as assessed by signs and symptoms, laboratory studies and rapid progression of disease, which leading to a clinical indication for chemotherapy.
- •History of CHF of any New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment (exception, atrial fibrillation, paroxysmal supraventricular tachycardia);
- •History of myocardial infarction within 6 months of randomization
- •History of LVEF decline to below 50% during or after prior trastuzumab neo-adjuvant or adjuvant therapy
- •Pregnant or lactating women;
- •QT interval>470 ms；
- •Serious concomitant diseases (including severe hypertension, severe diabetes, active infection, thyroid disease, etc.) that are harmful to the patient's safety or affect the patient's completion of the study;
研究组 & 干预措施
Pyrotinib and trastuzumab plus aromatase inhibitor
Participants will receive pyrotinib in combination with trastuzumab plus AI until pre-defined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
干预措施: Pyrotinib (Drug)
Pyrotinib and trastuzumab plus aromatase inhibitor
Participants will receive pyrotinib in combination with trastuzumab plus AI until pre-defined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
干预措施: Trastuzumab (Drug)
Pyrotinib and trastuzumab plus aromatase inhibitor
Participants will receive pyrotinib in combination with trastuzumab plus AI until pre-defined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
干预措施: Aromatase inhibitor (Drug)
Trastuzumab plus aromatase inhibitor
Participants will receive trastuzumab plus AI until pre-defined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
干预措施: Trastuzumab (Drug)
Trastuzumab plus aromatase inhibitor
Participants will receive trastuzumab plus AI until pre-defined study end, disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
干预措施: Aromatase inhibitor (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: From randomization to 36 month
PFS was defined as the time from randomization to first documented disease progression (PD) using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) or death from any cause, whichever occurred first. For target lesions, PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. The PFS will be will be estimated using Kaplan-Meier method. A Kaplan-Meier curve, median PFS, hazard ratio with appropriate confidence intervals will be reported.
次要结局
- Time to Response (TTR)(From randomization to 36 month)
- Overall Survival (OS)(From randomization to 36 month)
- Objective Overall Response Rate (ORR)(From randomization to 36 month)
- Adverse events (AEs)(From screening phase until AEs returns to Grade 0-1 or baseline)
- Duration of Response (DoR)(From randomization to 36 month)
- Clinical Benefit Response (CBR)(From randomization to 36 month)
- Quality of Life (QoL) by FACT-B(From randomization to 36 month)
- Quality of Life (QoL) by EQ-5D(From randomization to 36 month)
研究者
Qiang SUN
Professor
Peking Union Medical College Hospital