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