Pyrotinib Plus Vinorelbine in Participants With HER2-positive Previously Treated Locally Advanced or Metastatic Breast Cancer

Study Overview
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Brief Summary
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The purpose of this study is to identify the highest tolerable dose of pyrotinib in combination with vinorelbine and to assess the safety and efficacy of the combination in Patients With HER2-Positive Locally Advanced or Metastatic Breast Cancer. The study will be conducted in two parts. In the first part, testing will be done on up to 12 subjects to determine the highest tolerable dose of pyrotinib and vinorelbine in patients with advanced solid tumors. In the second part of the study, we will explore the safety and efficacy of Pyrotinib + vinorelbine in Patients With HER2-Positive Locally Advanced or Metastatic Breast Cancer Who Have Received Prior Trastuzumab-Based Therapy. Participants will be treated until disease progression (PD), unmanageable toxicity, or study termination.

Official Title
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A Single-arm, Multi-center Phase II Clinical Study of Pyrotinib Combined With Vinorelbine in the Treatment of HER2-positive and Treated Metastatic Breast Cancer

Conditions
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Breast Cancer, Pyrotinib, Breast Diseases, Vinorelbine, HER2-positive Breast Cancer

Intervention / Treatment
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* Drug: Pyrotinib 320mg + Vinorelbine
* Drug: Pyrotinib 400mg + Vinorelbine
* Drug: Pyrotinib plus Vinorelbine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed invasive breast cancer HER2 status must be prospectively, centrally tested and be HER2-positive based on central laboratory assay results Prior treatment for breast cancer in the adjuvant, unresectable, locally advanced, or metastatic setting must include both a taxane, alone or in combination with another agent, and trastuzumab, alone or in combination with another agent. Patients who have previously used pertuzumab will be allowed. Documented progression (which occur during or after most recent treatment or within 6 months after completing of adjuvant therapy) of incurable, unresectable, locally advanced or metastatic breast cancer, defined by the investigator Measurable and/or nonmeasurable disease; participants with central nervous system-only disease are excluded Cardiac ejection fraction greater than or equal to (>/=) 50 percent (%) by either echocardiogram or multi-gated acquisition scan Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Exclusion Criteria: History of treatment with pyrotinib Prior treatment with lapatinib or neratinib History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma History of receiving any anti-cancer drug/biologic or investigational treatment within 28 days prior to randomization except hormone therapy Recovery of treatment-related toxicity consistent with other eligibility criteria History of radiation therapy within 28 days of randomization Brain metastases that are untreated, symptomatic, or require therapy to control symptoms, as well as any history of radiation, surgery, or other therapy, including steroids, to control symptoms from brain metastases within 2 months (60 days) of randomization History of symptomatic congestive heart failure or serious cardiac arrhythmia requiring treatment History of myocardial infarction or unstable angina Current severe, uncontrolled systemic disease (for example, clinically significant cardiovascular, pulmonary, or metabolic disease) Pregnancy or lactation Current known active infection with human immunodeficiency virus (HIV) or hepatitis C virus Presence of conditions that could affect gastrointestinal absorption: Malabsorption syndrome, resection of the small bowel or stomach, and ulcerative colitis

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

Sexes Eligible for Study
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All

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pyrotinib plus vinorelbine<br> | Drug: Pyrotinib 320mg + Vinorelbine<br>* pyrotinib 320mg tablets administered daily by mouth, vinorelbine(po) 80 mg/m2 weekly (following a first cycle at 60 mg/m2) administered on day 1 and day 8 of 21 day cycle. Treatment lasts for two cycles<br>Drug: Pyrotinib 400mg + Vinorelbine<br>* pyrotinib 400mg tablets administered daily by mouth, vinorelbine(po) 80 mg/m2 weekly (following a first cycle at 60 mg/m2) administered on day 1 and day 8 of 21 day cycle. Treatment lasts for two cycles<br>Drug: Pyrotinib plus Vinorelbine<br>* pyrotinib administered daily by mouth（MTD）, vinorelbine(po) 80 mg/m2 weekly (following a first cycle at 60 mg/m2) administered on day 1 and day 8 of 21 day cycle, or vinorelbine(iv) 25 mg/m2 on day 1 and day 8 of 21 day cycle. Treatments will lasts until disease progression (as assessed by the investigator) or unmanageable toxicity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS as Assessed by the Investigator | Progression-Free Survival | from enrollment to progression or death (for any reason), assessed up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | from enrollment to progression or death (for any reason), assessed up to 3 years | Ratio of CR and PR in all subjects | 
| OS | OS was defined as the time from the date of randomization to the date of death from any cause. | from enrollment to progression or death (for any reason), assessed up to 3 years |