Adjuvant Study of Pyrotinib in HER-2 Positive Breast Cancer

Study Overview
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Brief Summary
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This is a prospective, randomised, multicenter, no placebo-controlled, open label study for evaluating the efficacy and safety of pyrotinib in women with residual invasive HER2-positive breast cancer after neoadjuvant chemotherapy plus anti-HER2 target therapy. The main purpose is to investigate whether pyrotinib can further reduce the risk of recurrence from previously diagnosed HER-2 positive breast cancer based on the 1-year trastuzumab standard adjuvant treatment with or without pertuzumab.

Official Title
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Adjuvant Trastuzumab Plus Pyrotinib for Residual Invasive HER2-positive Breast Cancer After Neoadjuvant Chemotherapy Plus Anti-HER2 Target Therapy

Conditions
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Locally Advanced Breast Cancer

Intervention / Treatment
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* Drug: pyrotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female, Aged ≥18 and ≤70 years; Histologically confirmed invasive HER2 positive breast cancer, early disease(Stage ⅡA-Ⅲ) ; Completed neoadjuvant therapy, including chemotherapy and trastuzumab; Residual invasive disease was detected pathologically in the surgical specimen of the breast or axillary lymph nodes after completion of neoadjuvant chemotherapy; Been or being treated for early breast cancer with standard of care duration of trastuzumab; Adjuvant treatment regimen needs to be determined before randomization; Duration from Random time to the last use of trastuzumab≤1 year. Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1; Required laboratory values including following parameters:ANC: ≥ 1.5 x 109/L; Platelet count: ≥ 100 x 109/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 Signed informed consent form (ICF) . Exclusion Criteria: Metastatic disease (Stage IV) ; Gross residual disease remaining after mastectomy or positive margins after breast-conserving surgery; Progressive disease during neoadjuvant therapy; Subjects that are unable to swallow tablets, or dysfunction of gastrointestinal absorption; Treated or treating with anti-HER2 TKI, including but not limited to pyrotinib, lapatinib and neratinib. Less than 4 weeks from the last clinical trial; History of immunodeficiency, including HIV-positive, suffering from other acquired, congenital immunodeficiency disease, or history of organ transplantation; Subjects had any heart disease, including: (1) angina; (2) requiring medication or clinically significant arrhythmia; (3) myocardial infarction; (4) heart failure; (5) Any heart diseases judged by investigator as unsuitable to participate in the trial; Female patients who are pregnancy, lactation or women who are of childbearing potential tested positive in baseline pregnancy test;Female patients of childbearing age that are reluctant to take effective contraceptive measures throughout the trial period; Evidence of significant medical illness that in the investigator's judgment will substantially increase the risk associated with the subject's participation in and completion of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pyrotinib<br>pyrotinib 400 mg, orally once daily for one year | Drug: pyrotinib<br>* pyrotinib 400 mg, orally once daily for one year<br>|
| No Intervention: No Pyrotinib<br>Observation follow-up | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Invasive Disease-free Survival (iDFS) | Invasive disease-free survival time is defined as the time from date of randomization until the first invasive disease recurrence of the following events: invasive ipsilateral breast tumor recurrence, invasive contralateral breast cancer, local/regional invasive recurrence, distant recurrence and death from any cause. | From randomization until time of event up to 2 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free Survival (DFS) | Disease-free survival time is defined as the time from date of randomization until the first disease recurrence of the following events: invasive ipsilateral breast tumor recurrence, invasive contralateral breast cancer, local/regional invasive recurrence, non-breast primary invasive cancer, ductal carcinoma in situ(DCIS),or distant recurrence and death from any cause | From randomization until time of event up to 2 years | 
| Overall Survival (OS) | Overall survival is defined as the time from randomization to death from any cause. | From randomization until time of event up to 2 years |