Neoadjuvant Study of Pyrotinib and Trastuzumab Plus Vinorelbine in Trastuzumab-refractory HER2-Positive Breast Cancer.

Study Overview
=================
Brief Summary
-----------------
This study is a single-arm, prospective, open label clinical study for evaluating the efficacy and safety of neoadjuvant pyrotinib and trastuzumab plus Vinorelbine given as neoadjuvant treatment in Trastuzumab-refractory HER2 positive early stage or locally advanced breast cancer.

Detailed Description
-----------------
Neoadjuvant therapy is the standard treatment for locally advanced breast cancer and is used to reduce tumors to make them operable, and to increase breast-conserving rates. In recent years, the anti-HER2 treatment mode, which is double-blocked by a combination of dual-targeted drugs, has obtained clinical approval in adjuvant therapy and neoadjuvant therapy. Pyrotinib is an oral tyrosine kinase inhibitor targeting both HER-1 and HER-2 receptors. Based on previous clinical studies, we designed the study to explore the possibility of Pyrotinib in combination with Trastuzumab plus Vinorelbine given as neoadjuvant treatment in HER2 positive early stage or locally advanced breast cancer.

Official Title
-----------------
Neoadjuvant Study of Pyrotinib in Combination With Trastuzumab Plus Vinorelbine in Trastuzumab-refractory HER2-Positive Early Stage or Locally Advanced Breast Cancer Patients.

Conditions
-----------------
HER2 Positive Breast Cancer

Intervention / Treatment
-----------------
* Drug: Pyrotinib and Trastuzumab plus Vinorelbine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. female patients, 18 years ≤ age ≤ 75 years. 2. Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1. 3. Histologically confirmed invasive breast cancer:early stage or locally advanced,Primary tumour greater than 2 cm diameter 4. HER2 positive (HER2+++ by IHC or FISH+) 5. Subjects received neoadjuvant therapy with trastuzumab 2 weeks post-imaging evaluation Patients with a price of PD or SD. 6. Known hormone receptor status. 7. Required laboratory values including following parameters: 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: ≤ 1.5 x ULN (or ≤ 5×ULN in patients with liver metastases);BUN and creatine clearance rate: ≥ 50 mL/min;LVEF: ≥ 50%;QTcF: < 470 ms for female and < 450 ms for male. 8. Signed the informed consent form prior to patient entry. Exclusion Criteria: - 1. metastatic disease (Stage IV) or inflammatory breast cancer. 2. 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. 3. clinically relevant cardiovascular disease:Known history of uncontrolled or symptomatic angina, clinically significant arrhythmias, congestive heart failure, transmural myocardial infarction, uncontrolled hypertension ≥180/110); 4. Unable or unwilling to swallow tablets.

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

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pyrotinib + trastuzumab +Vinorelbine<br>Pyrotinib in Combination With Trastuzumab Plus Vinorelbine | Drug: Pyrotinib and Trastuzumab plus Vinorelbine<br>* Pyrotinib:400mg orally daily Trastuzumab:8mg/kg ivgtt load followed by 6mg/kg ivgtt 3-weekly for a total of 4 cycles Vinorelbine :25mg/m2 ivgtt 3-weekly for a total of 4 cycles,d1 d8<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Objective Response Rate | [Time Frame: Baseline up to cycle 4 (assessed at Baseline, at the time of pre-surgery)up to approximately 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological Complete Response (pCR) | Percentage of Participants With Pathological Complete Response (pCR) at the Time of Surgery evaluated | Time Frame: through study completion, an average of 1 year | 
| EFS | Event-free survival | Time Frame: Following surgery until Year 5 | 
| DFS | Disease-free Survival | Time Frame: Following surgery until Year 5 | 
| DDFS | Distance Disease-free Survival | Time Frame: Following surgery until Year 5 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Trastuzumab-refractory