A Phase II Study to Evaluate the Efficacy and Safety of Anti-HER2 Triple-targeted Drugs Combined With CDK4/6 Inhibitors in Neoadjuvant Therapy for ER-positive HER2-positive Breast Cancer Patients.
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 42
- 主要终点
- pCR
研究概览
简要总结
To further enhance treatment efficacy, minimize reliance on chemotherapy, and identify the optimal neoadjuvant approach for ER-positive and HER2-positive population, we have designed a single-arm, phase II clinical trial. This study aims to evaluate the efficacy and safety of a novel regimen integrating CDK4/6 inhibitors intensified endocrine therapy and dual HER2-targeted monoclonal antibodies plus the tyrosine kinase inhibitor pyrotinib.
详细描述
In patients with ER-positive and HER2-positive breast cancer, the therapeutic potential of combining trastuzumab, pertuzumab, and pyrotinib-representing a triple-targeted anti-HER2 strategy-alongside intensified endocrine therapy( with CDK4/6 inhibitors )has not yet been established. To further enhance treatment efficacy, minimize reliance on chemotherapy, and identify the optimal neoadjuvant approach for this patient population, we have designed a single-arm, phase II clinical trial. This study aims to evaluate the efficacy and safety of a novel regimen integrating CDK4/6 inhibitors intensified endocrine therapy and dual HER2-targeted monoclonal antibodies plus the tyrosine kinase inhibitor pyrotinib.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Women aged 18 to 70 years with breast cancer eligible for neoadjuvant therapy
- •Clinically staged as II-III
- •Histologically confirmed unilateral invasive breast cancer with HER2 positivity, defined as HER2 immunohistochemistry 3+ or in situ hybridization (FISH)-confirmed amplification
- •Estrogen receptor (ER) expression ≥10% by immunohistochemistry
- •Postmenopausal status
- •Premenopausal or perimenopausal patients must undergo surgical oophorectomy or receive ovarian function suppression with gonadotropin-releasing hormone (GnRH) agonists
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Left ventricular ejection fraction (LVEF) ≥50% and corrected QT interval (QTc) ≤470 ms
- •Adequate major organ function, as evidenced by the following laboratory parameters:
- •(1) Hematologic function: hemoglobin (Hb) ≥90 g/L (without transfusion within 14 days), absolute neutrophil count (ANC) ≥1.5×10⁹/L, platelet count (PLT) ≥100×10⁹/L; (2) Hepatic and renal function: total bilirubin (TBIL) ≤1.5×upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3×ULN, serum creatinine ≤1×ULN, and calculated creatinine clearance >50 mL/min using the Cockcroft-Gault formula 10) Willingness to participate in the study, provision of signed informed consent, and demonstrated ability to comply with study procedures and follow-up visits
排除标准
- •HER2-negative disease, defined as immunohistochemistry (IHC) score of 0 or 1+; or IHC 2+ without amplification by fluorescence in situ hybridization (FISH)
- •Prior receipt of neoadjuvant therapy or any systemic or non-surgical local treatment, including chemotherapy, targeted therapy, radiotherapy, or endocrine therapy
- •History of another malignancy, except for adequately treated basal cell carcinoma of the skin or cervical carcinoma in situ
- •Inflammatory breast cancer, bilateral breast cancer, or presence of distant metastases
- •Pregnant or breastfeeding women, or women of childbearing potential who are unwilling or unable to use effective contraception during the study period
- •Concurrent participation in another interventional clinical trial
- •Significant organ dysfunction, including cardiac, pulmonary, hepatic, or renal impairment; left ventricular ejection fraction (LVEF) <50% on echocardiography; history of major cardiovascular or cerebrovascular events within 6 months prior to enrollment (e.g., unstable angina, chronic heart failure, myocardial infarction, or stroke); uncontrolled hypertension (>150/90 mmHg); or poorly controlled diabetes mellitus
- •Current use of strong CYP3A4 inhibitors or inducers, including:
- •Strong inhibitors: boceprevir, clarithromycin, conivaptan, delavirdine, indinavir, itraconazole, ketoconazole, ritonavir, mibefradil, miconazole, trazodone, nelfinavir, posaconazole, saquinavir, telaprevir, telithromycin, voriconazole, grapefruit, grapefruit juice, or grapefruit-containing products
- •Strong inducers: carbamazepine, phenytoin, primidone, rifampicin, and St. John's wort
- •Active, severe, or uncontrolled infection, or fever of unknown origin during the screening period
- •History of substance abuse involving psychotropic agents with ongoing dependence, or history of significant psychiatric disorder that may impair compliance or safety
- •Deemed unsuitable for study participation by the treating investigator
研究组 & 干预措施
triple-targeted anti-HER2
trastuzumab, pertuzumab, and pyrotinib combined with CDK4/6 inhibitor and endocrine therapy
干预措施: triple-targeted anti-HER2 and CDK4/6 inhibitor (Drug)
结局指标
主要结局
pCR
时间窗: 3 years
pathological response rate
次要结局
- EFS(3 years)
- iDFS(3 years)
- RFS(3 years)
- DDFS(3 years)
- OS(3 years)
- adverse events(3 years)