Neoadjuvant Study of Pyrotinib in Combination With Trastuzumab in Patients With HER2 Positive Breast Cancer

Study Overview
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Brief Summary
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This is a randomised, double-blind multicenter Phase III study for evaluating the efficacy and safety of neoadjuvant pyrotinib and trastuzumab plus docetaxel versus placebo and trastuzumab plus docetaxel given as neoadjuvant treatment in HER2 positive early stage or locally advanced breast cancer.

Official Title
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A Randomized, Muticenter Double-blind Phase III Study of Neoadjuvant Pyrotinib Plus Trastuzumab and Docetaxel Compared With Placebo Plus Trastuzumab and Docetaxel 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
* Drug: Placebo Oral Tablet
* Drug: Trastuzumab
* Drug: Docetaxel


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）:Primary tumour greater than 2 cm diameter 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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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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: arm1<br>Pyrotinib Plus trastuzumab and docetaxel | Drug: Pyrotinib<br>* pyrotinib: 400mg orally daily;<br>Drug: Trastuzumab<br>* trastuzumab:8mg/kg iv load followed by 6mg/kg iv 3-weekly for a total of 4 cycles;<br>Drug: Docetaxel<br>* docetaxel:after the biological window, 100mg/m2 for a total of 4 cycles<br>|
| Placebo Comparator: arm2<br>placebo plus trastuzumab and docetaxel | Drug: Placebo Oral Tablet<br>* placebo: 400mg orally daily;<br>Drug: Trastuzumab<br>* trastuzumab:8mg/kg iv load followed by 6mg/kg iv 3-weekly for a total of 4 cycles;<br>Drug: Docetaxel<br>* docetaxel:after the biological window, 100mg/m2 for a total of 4 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) at the Time of Surgery evaluated by independent review committee(IRC) |  | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Pathological Complete Response (pCR) at the Time of Surgery evaluated by sites |  | Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4,each cycle is 21 days) | 
| Event-free survival(EFS) |  | Following surgery until Year 3 | 
| Disease-free Survival (DFS) |  | Following surgery until Year 3 | 
| Distance Disease-free Survival (DDFS) |  | Following surgery until Year 3 | 
| Objective Response Rate (ORR) during neoadjuvant period |  | Baseline up to cycle 4 (assessed at Baseline, at the time of pre-surgery)up to approximately 12 months |