Neoadjuvant Study of Pyrotinib in Patients With HER2 Positive Breast Cancer

Study Overview
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Brief Summary
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This is a randomized, double-blind multicenter Phase III study for evaluating the efficacy and safety of neoadjuvant pyrotinib and trastuzumab plus docetaxel and Carboplatin versus placebo and trastuzumab plus docetaxel and Carboplatin given 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 (Placebo +Trastuzumab+Docetaxel+ Carboplatin) in neoadjuvant chemotherapy. It is proposed that 100 participants will be enrolled in this study. The target population is women with early breast cancer (stage of T1-4N0-3M0) 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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Neoadjuvant Study of Pyrotinib in Combination With Trastuzumab Plus Docetaxel and Carboplatin in Patients With HER2 Positive Early Stage or Locally Advanced Breast Cancer: a Single-arm, Ahead, Open-label Study

Conditions
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Breast Cancer, Neoplasm, Breast, Breast Diseases

Intervention / Treatment
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* Drug: Pyrotinib
* Drug: Trastuzumab
* Drug: Docetaxel
* Drug: Carboplatin
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: female patients, 18 years ≤ age ≤ 80 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: 80 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Experimental: Pyrotinib (400mg orally daily)+Trastuzumab (8mg/kg iv load followed by 6mg/kg iv 3-weekly)+Docetaxel (75mg/m2)+ Carboplatin(AUC=5), for a total of 6 cycles. Placebo Comparator: Placebo Oral Tablet (400mg orally daily)+Trastuzumab (8mg/kg iv load followed by 6mg/kg iv 3-weekly)+Docetaxel (75mg/m2)+ Carboplatin(AUC=5), for a total of 6 cycles.
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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