Neoadjuvant Chemotherapy With Pyrotinib, Epirubicin and Cyclophosphamide Followed by Taxanes and Trastuzumab for HER-2+ Breast Cancer

Study Overview
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Brief Summary
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This is a prospective, open label, parallel controlled study to evaluate the efficacy and safety of neoadjuvant pyrotinib in HER2+ breast cancer patients

Official Title
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Neoadjuvant Chemotherapy With Pyrotinib, Epirubicin and Cyclophosphamide Followed by Taxanes and Trastuzumab for HER2+Breast Cancer: a Multicenter, Randomized, Open-label, Parallel-Group Controlled Trial

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Pyrotinib
* Drug: Epirubicin
* Drug: Cyclophosphamide
* Drug: Taxanes
* Biological: Trastuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female breast cancer patients at the age of >= 18 years and <= 65 years who received first treatment； Pathologically confirmed HER2-positive invasive breast cancer（which is defined as the immunohistochemistry score of > 10% immunoreactive cells being 3+ or in situ hybridization results showing HER2 gene amplification），regardless of hormone receptor status (ER and PR)； According to the 2019 CSCO BC guidelines: When HER-2 positive is used as the standard for preoperative neoadjuvant therapy for breast cancer, the tumor is larger than 2 cm； The Eastern Tumor Collaborative Group (ECOG) has a physical status score of ≤1； The functional level of the main organs must meet the following requirements ： 1) blood routine test: hemoglobin (Hb) ≥ 90g/L;Neutrophils (ANC) ≥ 1.5 × 10^9/L; platelet count (PLT) ≥ 90 × 10^9/L; 2) Blood biochemistry: Total bilirubin (TBIL) ≤ 1.5 upper limit of normal value (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) Heart color ultrasound: Left ventricular ejection fraction (LVEF) ≥ 55%; Women of childbearing age, tested negative for serum pregnancy test 7 days before randomization，and willing to use appropriate methods during the trial and within 8 weeks after the last administration of the test drug; A volunteer to participate in the study; provision of written informed consent; good compliance and willing to cooperate during the follow-up. Exclusion Criteria: Known history of hypersensitivity to pyrotinib or any of it components; Patients have previously received antitumor treatment or radiation therapy for any malignant tumor (except for cervical carcinoma in situ and basal cell carcinoma that have been cured); Patients underwent major breast cancer-free surgery within 4 weeks and have not fully recovered; Subjects that are unable to swallow tablets,intestinal obstruction or dysfunction of gastrointestinal absorption; Patients with severe heart disease or discomfort who cannot be treated; The patient suffers from mental illness or psychotropic substance abuse and cannot cooperate; Pregnant or lactating women; Less than 4 weeks from the last clinical trial; Patients participating in other clinical trials at the same time The researchers think inappropriate.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group<br>Patients will receive the test drug (Pyrotinib) combined with Epirubicin and Cyclophosphamide followed by Taxanes and Trastuzumab | Drug: Pyrotinib<br>* 400mg administered as continuous oral once daily from the first day of the study<br>Drug: Epirubicin<br>* 90mg/m^2 d1 iv Q2W for 4 cycles<br>Drug: Cyclophosphamide<br>* 600 mg/m^2 d1 iv Q2W for 4 cycles<br>Drug: Taxanes<br>* Albumin paclitaxel（125mg/m2 d1、8 iv Q3W for 4 Cycles）/Docetaxel(100mg/m2 d1 iv Q3W for 4 Cycles )<br>Biological: Trastuzumab<br>* the first cycle is a loading dose of 8 mg / kg, followed by 6 mg / kg. Iv Q3W for 1 year<br>|
| Active Comparator: Control group<br>Patients will only receive Epirubicin and Cyclophosphamide followed by Taxanes and Trastuzumab | Drug: Epirubicin<br>* 90mg/m^2 d1 iv Q2W for 4 cycles<br>Drug: Cyclophosphamide<br>* 600 mg/m^2 d1 iv Q2W for 4 cycles<br>Drug: Taxanes<br>* Albumin paclitaxel（125mg/m2 d1、8 iv Q3W for 4 Cycles）/Docetaxel(100mg/m2 d1 iv Q3W for 4 Cycles )<br>Biological: Trastuzumab<br>* the first cycle is a loading dose of 8 mg / kg, followed by 6 mg / kg. Iv Q3W for 1 year<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological Complete Response rate(pCR) | pathological complete response | within 3 weeks after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate(ORR) | Baseline to measured stable disease | 2 years | 
| Event Free Survival(EFS) | Baseline to the occurrence of any event | 3 years | 
| Disease-free survival(DFS) Baseline to measured date of recurrence or death from any cause | Baseline to measured date of recurrence or death from any cause | 3 years | 
| Overall survival (OS) | Baseline to measured date of death from any cause | 5 years |