Screening Plasma HER2 Amplication by Digital PCR in Advanced Breast Cancer Patients Treated With Trastuzumab and Pyrotinib

Study Overview
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Brief Summary
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The hypothesis of this study is to discover the efficacy and safety of trastuzumab combined with pyrotinib in treating advanced breast cancer with HER2 positive, which is detected by digital PCR. It is a single-arm, multicenter phase II clinical study. The purpose of this study is: To explore the Response rate (RR) and progression-free survival(PFS) and safety of patients with recurrent metastatic breast cancer who received trastuzumab combined with pyrotinib in positive plasma HER2 amplification detected by digital PCR. To explore the potential using of digital PCR in recurrent and metastatic breast cancer.

Detailed Description
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The purpose of this study is: To explore the Response rate (RR) and progression-free survival(PFS) and safety of patients with recurrent metastatic breast cancer who received trastuzumab combined with pyrotinib in positive plasma HER2 amplification detected by digital PCR. To explore the potential using of digital PCR in recurrent and metastatic breast cancer.

Official Title
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Screening Plasma HER2 Amplication by Digital PCR in Advanced Breast Cancer Patients Treated With Trastuzumab and Pyrotinib

Conditions
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Advanced Breast Cancer

Intervention / Treatment
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* Drug: Trastuzumab and Pyrotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with recurrent or distant metastatic breast cancer whose primary tissue was negative for HER2 amplification, and newly diagnosed patients with stage IV breast cancer who were negative for HER2 amplification; All enrolled patients had previously received ≥ second-line therapy; Note: ① negative expression of HER2 refers to the primary tissue tested by IHC/FISH (clinical report), and the cell immunohistochemical staining intensity is 0,1 + or 2+, but negative by fluorescence in situ hybridization (FISH). Age range 18-75, female; Good physical strength: ECOG score 0-1; Expected survival of more than 3 months; The patient had no major organ dysfunction;Include: Routine blood The ANC acuity 1.5 x 109 / L;PLT acuity 90 x 109 / L;Hb 90 g/L or higher; Blood biochemical 1.5 x ULN TBIL or less;ALT and AST 2 x ULN or less;ALT and AST≤5×ULN in patients with liver metastases;BUN and Cr≤1.5×ULN and creatinine clearance ≥50 mL/min (Cockcroft-Gault formula); Heart colour to exceed LVEF 50% or higher;Fridericia adjusted QT interval (QTcF) for 12-lead electrocardiogram in men < 450 ms and in women < 470 ms. Evaluable tumor lesions according to RECIST 1.1 criteria; Voluntarily join the group, agree and sign the written informed consent. Exclusion Criteria: Patients who have previously received anti-HER2 therapy, or who have received a study drug or preparation/treatment (i.e., participating in another trial) within 4 weeks prior to enrollment; Patients who are allergic to study drugs or unable to take them orally;Patients who refuse the medication regimen; Serious dysfunction of vital organs (heart, liver, kidney);Clinically significant heart disease, i.e., New York Heart Association (NYHA) grade ⅲ - ⅳ heart failure or more severe congestive heart failure or severe arrhythmias requiring pharmacological intervention;Uncontrollable angina pectoris, uncontrolled arrhythmia or uncontrolled hypertension, myocardial infarction within 6 months as confirmed by electrocardiogram (ECG);Previous history of organ transplantation, splenectomy; Patients with other malignancies, except for cured non-melanoma skin cancers, cervical carcinoma in situ and other tumors that have been cured for at least 5 years; Pregnant and lactating women (women of childbearing age are subject to pregnancy tests), fertile women with positive baseline pregnancy tests, or women of childbearing age who are unwilling to use effective contraception throughout the study period.; In the active period of other acute infectious diseases or chronic infectious diseases; A history of uncontrolled epilepsy, central nervous system disease or mental disorder; Persons with disabilities of consciousness and other legal capacity or legal capacity limited; A known history of human immunodeficiency virus; Other conditions that the investigator considers inappropriate for the patient to participate in the study.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Arm<br>Trastuzumab and Pyrotinib | Drug: Trastuzumab and Pyrotinib<br>* Trastuzumab: 3-week dosing regimen, The initial load dose was 8 mg/kg. Pyrotinib: 400 mg orally once daily, take it continuously, every 21 days as a cycle. Use until intolerable toxicity or disease progression occurs.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate(ORR) | The ORR will be defined as the proportion of patients in the Efficacy Evaluable patient Set who achieve complete response (CR) and partial response (PR) | up to 1 year after the last patient enrolled | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival(PFS) | PFS will be defined as the time from first dose of study drug until documentation of disease progression or death from any cause | up to 1 year after the last patient enrolled | 
| Incidence and Severity of adverse events | hematologic, hepatotoxicity, Incidence of hypertension, Incidence of proteinuria | approximately 1.5 years |