Neoadjuvant Study of Pyrotinib and Trastuzumab Plus Chemotherapy in Patients With HER2 Positive Breast Cancer

Study Overview
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Brief Summary
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This is a prospective, open-label,multicenter Phase II study for evaluating the efficacy and safety of neoadjuvant pyrotinib and trastuzumab plus chemotherapy as neoadjuvant treatment in HER2 positive early stage or locally advanced breast cancer.

Detailed Description
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The investigators hypothesized that the experimental group (Pyrotinib+Trastuzumab+Docetaxel+ Carboplatin) could have a higher Pathological Complete Response (pCR) rate than the control group (Trastuzumab+Docetaxel+ Carboplatin) in neoadjuvant chemotherapy. It is proposed that 268 participants will be enrolled in this study. The target population is women with early breast cancer (stage of T2-3N0-3M0) who are eligible for primary systemic therapy. The primary objective of the trial is to determine the pCR rate. The secondary objective of the trial is to determine the Event-free survival(EFS), Disease-free Survival (DFS), Distance Disease-free Survival (DDFS), Objective Response Rate (ORR) rate.

Official Title
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A Prospective, Open-label,Multicenter Phase II Study of Neoadjuvant Pyrotinib Plus Trastuzumab and Chemotherapy in Women With HER2 Positive Early Stage or Locally Advanced Breast Cancer

Conditions
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HER2-positive Breast Cancer

Intervention / Treatment
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* Drug: Pyrotinib+Trastuzumab+Docetaxel+Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: female patients, 18 years ≤ age ≤75 years； Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1; Histologically confirmed invasive breast cancer（early stage or locally advanced） HER2 positive (HER2+++ by IHC or FISH+) Known hormone receptor status. Cardiovascular: Baseline left ventricular ejection fraction (LVEF)≥55% measured by ECHO Signed informed consent form (ICF) Exclusion Criteria: Metastatic disease (Stage IV) or inflammatory breast cancer. Previous or current history of malignant neoplasms, except for curatively treated: Basal and squamous cell carcinoma of the skin, Carcinoma in situ of the cervix. Clinically relevant cardiovascular disease: Known history of uncontrolled or symptomatic angina, clinically significant arrhythmias, congestive heart failure, transmural myocardial infarction, uncontrolled hypertension ≥180/110); Unable or unwilling to swallow tablets.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Interventional Model Description: Pyrotinib (400mg orally daily)+Trastuzumab (8mg/kg iv load followed by 6mg/kg iv 3-weekly)+Docetaxel (75mg/m2)+ Carboplatin(AUC=5/6), for a total of 4 cycles.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pyrotinib+Trastuzumab+Docetaxel+Carboplatin<br> | Drug: Pyrotinib+Trastuzumab+Docetaxel+Carboplatin<br>* Drug: Pyrotinib Pyrotinib: 400mg orally daily Drug: Trastuzumab Trastuzumab:8mg/kg iv load followed by 6mg/kg iv 3-weekly for a total of 6 cycles; Drug: Docetaxel Docetaxel: 75mg/m2 for a total of 6 cycles Drug: Carboplatin Carboplatin: AUC=5 or 6 for a total of 6 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Pathological Complete Response (pCR) |  | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free survival |  | Following surgery until Year 3 | 
| Disease-free Survival |  | Following surgery until Year 3 | 
| Distance Disease-free Survival |  | Following surgery until Year 3 | 
| Objective Response Rate |  | Baseline up to cycle 4 (assessed at Baseline, at the time of pre-surgery) up to approximately 12 months |