Trastuzumab Emtansine (T-DM1) in HER2-positive Breast Cancer Patients With Progressive Disease After TKIs or HP Therapy

Study Overview
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Brief Summary
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The goal of this clinical trial is to learn about the efficacy and safety of trastuzumab emtansine (T-DM1) in the treatment of patients with advanced HER2-positive breast cancer after TKIs or HP therapy. The main questions it aims to answer are: The objective response rate of patients receiving T-DM1 therapy with advanced HER2-positive breast cancer after TKIs or HP therapy. The adverse events and prognosis of patients with advanced HER2-positive breast cancer who receive the T-DM1 therapy. Changes of anti-tumor immunity during T-DM1 therapy in patients with advanced HER2-positive breast cancer. Participants will receive T-DM1 treatment (3.6mg/kg, d1/21, IVD) until progressive diseases or intolerable adverse effects occurs.

Official Title
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Trastuzumab Emtansine (T-DM1) Treatment in HER2-positive Breast Cancer Patients With Progressive Disease After TKIs or HP Therapy: a Multicenter, Single-arm, Phase II Study

Conditions
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Advanced Breast Cancer, Objective Response Rate, Trastuzumab Emtansine

Intervention / Treatment
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* Drug: Trastuzumab Emtansine (T-DM1)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years; pregnancy test (-) for premenopausal and perimenopausal patients, promising to use reliable contraception during treatment. Patients who were be diagnosed with invasive breast cancer according to the eighth edition of American Joint Committee on Cancer (AJCC) staging system, and develop disease progression after anti-HER2 therapy (TKIs) for stage IV disease at initial diagnosis or within one year of adjuvant anti-HER2 therapy (HP) after surgery for early breast cancer. At least one measurable lesion according to RECIST 1.1. ECOG score of 0 or 1. The organ function is still good and meets the following indicators: hemoglobin ≥ 90g/L, white blood cell ≥ 3.5×10^9/L, platelet ≥ 100×10^9/L, neutrophil ≥ 1.5×10^9/L, aspartate aminotransferase or alanine aminotransferase ≤ 3×ULN, total bilirubin ≤ 1.5×ULN, serum creatinine value ≤ 1.5×ULN. Without myocardial ischemia in ECG. NYHA grade I; Echocardiography LVEF ≥55%; Cardiac markers: cardiac troponin (cTnI) and brain natriuretic peptide (BNP) within normal range. Complete all necessary baseline laboratory and radiological tests prior to treatment. Complete clinical data. Exclusion Criteria: male breast cancer or inflammatory breast cancer. Patients who have other malignant tumors or have contracted malignant tumors other than breast cancer in the past 5 years, except for basal cell carcinoma of the skin or flat cell carcinoma and carcinoma in situ of the cervix that have been adequately treated and controlled. Accompanying other anti-tumor treatments or participating in other clinical trials. Serious diseases that will affect the patient's compliance or put the patient at risk. Major surgical procedures performed within 4 weeks prior to the commencement of study treatment or anticipated major surgical procedures during the course of the study. Patients who have used ADC drugs at present or before this study. History of allergic reactions or contraindications to use of any drug ingredient in this study. Patients with chronic diarrhea and intestinal obstruction, as well as other diseases that affect drug administration and absorption. Patients who have clinical cardiac symptoms or diseases that are not well controlled, such as: heart failure above NYHA 2; unstable angina; myocardial infarction occurred within one year; clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention. Dementia, intellectual abnormality, or any mental illness that interferes with the understanding of informed consent.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: T-DM1 treatment group<br>Trastuzumab Emtansine (T-DM1), 3.6mg/kg, d1/21, IVD, until progressive diseases or intolerable adverse effects occurs | Drug: Trastuzumab Emtansine (T-DM1)<br>* Enrolled patients will receive Trastuzumab Emtansine (T-DM1) treatment (3.6mg/kg, d1/21, IVD) until progressive diseases or intolerable adverse effects occurs.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate |  | up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | up to 36 months | 
| Overall survival |  | up to 36 months | 
| Adverse events |  | every 6 weeks | 
| Antitumor immunity related parameters | The changes of composition and function of immune cells in the tumor and peripheral blood before and after treatment | up to 12 weeks | 
| Tumor related parameters | Tumor heterogeneity before and after treatment its correlation with objective response rate, progression-free survival, overall survival, etc. | up to 12 weeks |