Phase II Neoadjuvant Pyrotinib Combined With Neoadjuvant Chemotherapy in HER2-low-expressing and HR Positive Early or Locally Advanced Breast Cancer: a Single-arm, Non-randomized, Single-center, Open Label Trial

Study Overview
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Brief Summary
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This is a single-arm, prospective, non-randomized, single-center, open label clinical study for evaluating the efficacy and safety of neoadjuvant pyrotinib combined with epirubicin and cyclophosphamide followed by docetaxel in HR positive and HER2-low-expressing early or locally advanced breast cancer.

Official Title
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Phase II Neoadjuvant Pyrotinib Combined With Neoadjuvant Chemotherapy in HER2-low-expressing and HR Positive Early or Locally Advanced Breast Cancer: a Single-arm, Non-randomized, Single-center, Open Label Trial

Conditions
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Breast Cancer, HER2-low-expressing Breast Cancer, Hormone Receptor-positive Breast Cancer, Neoadjuvant Therapy

Intervention / Treatment
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* Drug: Pyrotinib + epirubicin and cyclophosphamide followed by docetaxel treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent for all study according to local regulatory requirements prior to beginning specific protocol procedures Female patients, age ≥ 18 years Histologically confirmed unilateral primary carcinoma of the breast, except for occult breast cancer, inflammatory breast cancer without assessable focus or eczema like breast cancer HER2-low-positive (defined here as HER2 IHC 2+ and FISH-) and HR positive(defined here as ER and/or PR >1% stained cells) Tumour greater than 2 cm diameter or histologically (core- or fine-needle biopsy) involved lymph nodes According to RECIST version 1.1, there is at least one evaluable target lesion Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1 Required laboratory values including following parameters: WBC count:≥3.0 x 10^9/L ; ANC: ≥ 1.5 x 10^9/L; Platelet count: ≥ 100 x 10^9/L; Hemoglobin: ≥ 9.0 g/dL; Total bilirubin: ≤ 1.5 x upper limit of normal (ULN); ALT and AST: ≤ 2.5 x ULN; alkaline phosphatase ≤ 2.5 × ULN; Serum creatinine: ≤ 1.5 × ULN; Left ventricular ejection fraction (LVEF) ≥ 55% For female patients without menopause or surgical sterilization: consent to contraception both during the trial and within 6 months after the last administration of the test drug Exclusion Criteria: Metastatic disease (Stage IV) or bilateral breast cancer Known history of hypersensitivity to pyrotinib or any of it components According to the judgment of the researcher, other anti-tumor treatments (except for ovarian function inhibitors) are required during neoadjuvant therapy Patients with severe heart disease or discomfort who are expected to be unable to tolerate chemotherapy, including but not limited to these: 1). Fatal arrhythmia or higher grade atrioventricular block (second degree type 2 atrioventricular block or third degree atrioventricular block) 2). Unstable angina pectoris 3). Heart valve disease with clinical significance 4). ECG showed transmural myocardial infarction pain 5). Poor control of hypertension Patients underwent major breast cancer-free surgery within 4 weeks or have not fully recovered Serious or uncontrolled infections that may affect study treatment or evaluation of study results, including but not limited to active hepatitis virus infection, human immunodeficiency virus (HIV) antibody positive, lung infection, etc History of other malignant tumors in the past 5 years (excluding cured carcinoma in situ of cervix or skin basal cell carcinoma) Those with basic gastrointestinal diseases (especially long-term history of diarrhea or/and constipation)；Inability to swallow、intestinal obstruction or other factors will affect drug administration and absorption The investigator believes that the patient has any other conditions that are not suitable for participation in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pyrotinib<br>Experimental: Patients will receive Pyrotinib combined with Epirubicin and Cyclophosphamide followed by Docetaxel | Drug: Pyrotinib + epirubicin and cyclophosphamide followed by docetaxel treatment<br>* Drug: Pyrotinib pyrotinib 320mg orally daily Drug: Epirubicin epirubicin 90mg/m^2 d1 iv Q3W for 4 cycles Drug: Cyclophosphamide cyclophosphamide 600mg/m^2 d1 iv Q3W for 4 cycles Drug: Docetaxel docetaxel 100mg/m^2 d1 iv Q3W for 4 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Residual cancer burden 0/1 (RCB-0/1) rate | The percentage of patients with RCB-0/1 after neoadjuvant therapy | within 6 weeks after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological complete response (pCR) rate | The percentage of patients with pCR (ypT0/is, ypN0) after neoadjuvant therapy | within 6 weeks after surgery | 
| Objective response rate (ORR) | The percentage of subjects with CR or PR as the best response during the period from the beginning of the treatment to the progression of the disease or the completion of preoperative neoadjuvant therapy 【(CR+PR)/Analysis of the total number of people】 | within 6 weeks after surgery | 
| Breast conservation rate. | The breast conservation rate after treatment. | within 6 weeks after surgery | 
| Disease-free Survival (DFS) | The DFS is defined as the time from registration until any relapse, secondary malignancy, or death from any cause | 5 years | 
| Overall Survival (OS). | The OS is defined as the time from registration to death, irrespective of cause. | 5 years | 
| Biomarkers | Biomarkers: e.g. Tils | 5 years | 
| Incidence of grade 3-5 diarrhea. | Diarrhea were graded according to the National Cancer Institute's Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0. | before surgery |