A Prospective, Open, Multicenter Single-arm Clinical Studie of Docetaxel, Carboplatin Combined With Inetetamab and Pyrotinib in the Treatment of Local-advanced HER2-positive Breast Cancer

Overview

This study is a prospective, open, multi-center, single arm trial. The treatment group will receive six cycles of docetaxel, carboplatin combined with Inetetamab and Pyrotinib before surgery. By focusing on tpCR (ypT0/is, ypN0) evaluated by pathology, the efficacy of docetaxel, carboplatin combined with Inetetamab and Pyrotinib in the preoperative treatment of locally advanced HER2-positive breast cancer will be evaluated. During long-term follow-up, event-free survival (EFS), disease-free survival (DFS), distant metastasis-free survival (DDFS), overall survival (OS), central nervous system disease-free survival (CNSDFS) under this treatment regimen will be evaluated, and the efficacy-related biomarkers will be explored. The cardiotoxicity of Inetetamab and Pyrotinib in the treatment of breast cancer is also be evaluated.

Eligibility

Inclusion Criteria:

1. Female patients aged 18-75 years old;
2. ECOG score 0-1;
3. Breast cancer meets the following criteria: Histologically confirmed invasive breast cancer, primary tumor diameter > 2 cm as determined by standard evaluation methods at the research center; tumor stage: locally advanced;
4. HER2 expression-positive breast cancer confirmed by pathological examination;
5. Known hormone receptor status (ER and PR);
6. The functional level of major organs must meet the following requirements (no blood transfusion within 2 weeks before screening, no use of white blood cell and platelet-raising drugs):

        (1) Blood routine: neutrophil (ANC) >= 1.5×10^9/L; platelet count (PLT) >= 90×10^9/L;
        hemoglobin (Hb) >= 90 g/L; (2) Blood biochemistry: total bilirubin (TBIL) <= upper limit of
        normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=
        1.5×ULN; alkaline phosphatase <= 2.5×ULN; urea nitrogen (BUN) and creatinine (Cr) <=
        1.5×ULN; (3) Echocardiography: left ventricular ejection fraction (LVEF) >= 60%; (4)
        12-lead ECG: Fridericia-corrected QT interval (QTcF) < 470 msec; 7. Female patients who are
        not menopausal or surgically sterilized: agree to abstain from sex or use effective
        contraceptive methods during treatment and for at least 7 months after the last dose in the
        study treatment; 8. Voluntarily join the study, sign the informed consent, have good
        compliance and are willing to cooperate with follow-up.
        Exclusion Criteria:
          1. IV (metastatic) breast cancer;
          2. Received anti-tumor therapy or radiotherapy for any malignant tumor in the past,
             excluding cured cervical carcinoma in situ, basal cell carcinoma or squamous cell
             carcinoma and other malignant tumors;
          3. Receiving anti-tumor therapy in other clinical trials at the same time, including
             endocrine therapy, bisphosphonate therapy or immunotherapy;
          4. Received major surgical operations unrelated to breast cancer within 4 weeks before
             enrollment, or the patient has not fully recovered from such surgical operations;
          5. Severe cardiac disease or discomfort, including but not limited to the following: a
             history of heart failure or systolic dysfunction (LVEF < 60%); high-risk uncontrolled
             arrhythmias, such as atrial tachycardia, resting heart rate > 100 bpm , significant
             ventricular arrhythmia (eg, ventricular tachycardia) or higher-grade AV block (ie,
             Mobitz II second-degree AV block or third-degree AV block); antianginal medication
             indicated angina pectoris; clinically significant heart valve disease; transmural
             myocardial infarction on ECG; poorly controlled hypertension (systolic > 180 mmHg
             and/or diastolic > 100 mmHg);
          6. Inability to swallow, intestinal obstruction, or other factors that affect drug taking
             and absorption;
          7. Those who are known to have a history of allergy to the drug components of this
             regimen; have a history of immunodeficiency, including HIV positive test, or have
             other acquired or congenital immunodeficiency diseases, or have a history of organ
             transplantation;
          8. Female patients during pregnancy and lactation, female patients with fertility and
             positive baseline pregnancy test, or patients of childbearing age who are unwilling to
             take effective contraceptive measures during the entire trial period and within 7
             months after the last study drug;
          9. Have serious comorbidities or other comorbidities that would interfere with planned
             treatment, or any other condition that the investigator considers the patient
             unsuitable to participate in this study.