A Study of Pyrotinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in Patients With HER2+Metastatic Breast Cancer Who Have Prior Received Anthracyclin, Taxane or Trastuzumab

Study Overview
=================
Brief Summary
-----------------
Pyrotinib is an oral tyrosine kinase inhibitor targeting both HER-1 and HER-2 receptors. This study is a randomized, multi-center, multinational, open-label, active-controlled, parallel design study of the combination of pyrotinib plus capecitabine versus the combination of lapatinib plus capecitabine in HER2+ MBC patients who have prior received anthracyclin, taxane or trastuzumab. Patients will be stratified by weather have prior use of trastuzumab and randomized in a 1:1 ratio to one of the following treatment arms: Arm A: pyrotinib (400 mg once daily) + capecitabine (1000 mg/m^2 twice daily) Arm B: lapatinib (1250 mg once daily) + capecitabine (1000 mg/m^2 twice daily) Patients will receive either arm of therapy until the occurrence of death, disease progression, unacceptable toxicity, or other specified withdrawal criterion.

Official Title
-----------------
A Study of Pyrotinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in Patients With HER2+Metastatic Breast Cancer Who Have Prior Received Anthracyclin, Taxane or Trastuzumab

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

Intervention / Treatment
-----------------
* Drug: pyrotinib
* Drug: Lapatinib
* Drug: capecitabine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged ≥18 and ≤70 years. ECOG performance status of 0 to 1. Life expectancy of more than 12 weeks. At least one measurable lesion exists.(RECIST 1.1). Histologically or cytologic confirmed HER2 positive advanced breast cancer which failed prior therapies. 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;BUN and creatine clearance rate: ≥ 50 mL/min;LVEF: ≥ 50%;QTcF: < 470 ms for female and < 450 ms for male. Signed informed consent Exclusion Criteria: Received previous therapy with lapatinib, neratinib, pyrotinib or any other HER2 directe tyrosine kinase inhibitor. Received previous therapy with capecitabine within 3 months.

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

Sexes Eligible for Study
-----------------
All

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: pyrotinib plus capecitabine<br>pyrotinib(400 mg once daily) + capecitabine (2000 mg/m^2 daily, 1000 mg/m^2 BID) | Drug: pyrotinib<br> <br> Drug: capecitabine<br> <br> |
| Active Comparator: lapatinib plus capecitabine<br>lapatinib (1250 mg once daily) + capecitabine (2000 mg/m^2 daily, 1000 mg/m^2 BID) | Drug: Lapatinib<br> <br> Drug: capecitabine<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety(adverse Events [AEs] and Serious Adverse Events [SAEs]) |  | : From consent through 28 days following treatment completion (estimated 18 months) | 
| Objective Response Rate (ORR) |  | Estimated 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) |  | Estimated 18 months | 
| Time to Progression (TTP) |  | Estimated 18 months | 
| Duration of Response (DOR) |  | Estimated 18 months |