A Study of Pyrotinib Plus Capecitabine in Patients With HER2+ Metastatic Breast Cancer

Study Overview
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Brief Summary
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Pyrotinib is an oral tyrosine kinase inhibitor targeting both HER-1 and HER-2 receptors. This study is a randomized, multi-center, multinational, double blind, active-controlled, parallel design study of the combination of pyrotinib in combination with capecitabine versus placebo plus capecitabine in HER2+ MBC patients, who have prior received anthracyclin, taxane and trastuzumab. Patients will be randomized in a 2:1 ratio to one of the following treatment arms: Arm A: pyrotinib (400 mg once daily) + capecitabine (1000 mg/m^2 twice daily) Arm B: placebo (400 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. Patients in control group can be provide pyrotinib treatment when they progressed after the placebo plus capecitabine treatment.

Detailed Description
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This study is a phase 3, randomized, multi-center, multinational, double blind, active-controlled, parallel design study of the combination of pyrotinib in combination with capecitabine versus placebo plus capecitabine in HER2+ MBC patients, who have prior received anthracyclin, taxane and trastuzumab. Patients will be randomized in a 2:1 ratio to one of the following treatment arms: Arm A: pyrotinib (400 mg once daily) + capecitabine (1000 mg/m^2 twice daily) Arm B: placebo (400 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. Efficacy assessments will be performed at screening, every 6 weeks until cycle 18, every 12 weeks thereafter. Patients in control group can be provide pyrotinib treatment when they progressed after the placebo plus capecitabine treatment. Pyrotinb will be administrated until the patients reached progress again or wit

Official Title
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Pyrotinib Plus Capecitabine Versus Placebo Plus Capecitabine in Patients With HER2+ Metastatic Breast Cancer:a Randomised, Double-blind, Multicentre, Phase 3 Trial

Conditions
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HER2 Positive Metastatic Breast Cancer

Intervention / Treatment
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* Drug: pyrotinib
* Drug: placebo
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥18 and ≤75 years. ECOG performance status of 0 to 1. Life expectancy of more than 12 weeks. According to RECIST 1.1, at least one measurable lesion exists Histologically or cytologic confirmed HER2 positive advanced breast cancer which failed prior therapies. Prior treatment with trastuzumab(≥2 cycles in the metastatic setting, or ≥3 months in adjuvant setting), and the patients are not available for the trastuzumab or lapatinib Previously reveived both Anthracyclin and Taxane. Required laboratory values including following parameters: ANC: ≥ 1.5 x 10^9/L; Platelet count: ≥ 90 x 10^9/L; Hemoglobin: ≥ 9.0 g/dL; Total bilirubin: ≤ 1.5 x upper limit of normal (ULN); ALT and AST: ≤ 2 x ULN(patients with liver metastases: </= 5 x ULN); BUN and Creatinine: ≤ 1.5 x ULN;LVEF: ≥ 50%;QTcF: < 470 ms. 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. History of receiving chemotherapy, target-therapy or investigational treatment within 28 days prior to randomization. Received hormone therapy within 7 days prior to randomization. Brain metastases that are untreated, symptomatic, or require therapy to control symptoms. Current severe, uncontrolled systemic disease. 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: arm 1<br>pyrotinib plus capecitabine pyrotinib(400 mg once daily) + capecitabine (2000 mg/m^2 daily, 1000 mg/m^2 BID) | Drug: pyrotinib<br>* 400 mg once daily<br>Drug: Capecitabine<br>* 1000 mg/m2 per day on day 1 through 14, every 21 days.<br>|
| Active Comparator: arm 2<br>placebo plus capecitabine placebo(400 mg once daily) + capecitabine (2000 mg/m^2 daily, 1000 mg/m^2 BID) | Drug: placebo<br>* 400 mg once daily<br>Drug: Capecitabine<br>* 1000 mg/m2 per day on day 1 through 14, every 21 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) |  | Estimated 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) |  | Estimated 10 months | 
| Safety(adverse Events [AEs] and Serious Adverse Events [SAEs]) |  | From infromed consent through 28 days following treatment completion | 
| Duration of Response (DOR) |  | Estimated 10 months | 
| Clinical Benefit rate (CBR) |  | Estimated 10 months | 
| Overall Survival (OS) |  | Estimated 30 months |