Cardiac Safety and Efficacy for Early-stage Breast Cancer Patients Treated With Pegylated Liposomal Doxorubicin（PLD)

Study Overview
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Brief Summary
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This is a randomized, multicenter, open, controlled Post-Marketing Study. 272 early stage female breast cancer patients who were histopathology confirmed with adjuvant chemotherapy indications were enrolled in this study .The subjects will be randomly assigned to one of the two treatment groups at a 1: 1 ratio, and stratified by trastuzumab,age,baseline cardiac risk factors.

Detailed Description
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Subjects will receive one of two treatment regimens: Group A: intravenous infusion of pegylated liposomal doxorubicin（PLD） 35 mg/m2, d1; cyclophosphamide 600 mg/m2, intravenous infusion, d1; once every 21days, for 4 cycles. Sequential docetaxel 100 mg/m2, intravenous infusion, d1, or paclitaxel 80mg/m2,intravenous infusion, d1,8,15, once every 21 days, for 4 cycles. Group B: intravenous infusion of doxorubicin 60 mg/m2, d1; cyclophosphamide 600 mg/m2, intravenous infusion, d1; sequential docetaxel 100 mg/m2, intravenous infusion, d1, or paclitaxel 80mg/m2,intravenous infusion, d1,8,15, once every 21days, for 4 cycles. The primary endpoint is cardiotoxity,the secondary endpoint is 5-year disease-free survival (DFS), 5-year overall survival (OS), and safety: hematology and non hematological toxicity.

Official Title
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Cardiac Safety and Efficacy for Early-stage Breast Cancer Patients Treated With Pegylated Liposomal Doxorubicin（PLD）：an Dynamic Randomized, Positive Control, Open, Multicenter Clinical Study

Conditions
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Early Breast Cancer

Intervention / Treatment
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* Drug: PLD
* Drug: CTX
* Drug: Docetaxel
* Drug: Paclitaxel
* Drug: Doxorubicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.Subjects had histopathologically confirmed early stage breast cancer with adjuvant chemotherapy treatment evidence; 2.Age :18-75years old female; 3.High risk of recurrence: axillary lymph node-positive, or axillary lymph node negative with at least one of the following risk factors: triple negative breast cancer, histological grade III, the maximum tumor diameter> 5cm, Ki 67 ≥ 50%, vascular thrombosis positive; 4.ECOG score 0-1; 5.Expected survival time ≥ 12 months; 6.LVEF ≥ 55%; 7.Normal ECG, ST segment depression in patients such as coronary angiography, confirm <50% stenosis or incidental premature beats are acceptable; 8.Bone Marrow Function: ANC：≥1.5×109/L； PLT：≥100×109/L；Hb: ≥90g/L; 9.Liver and renal function:Serum creatinine ≤ normal upper limit (ULN) 1.5times; aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤ULN 2.5times; total bilirubin (TBil) level:≤ ULN 1.5 times, or ≤ ULN 2.5times if Gilbert's syndrome are present; 10.Subjects are well-behaved, able to undergo treatment and follow-up, and voluntarily comply with this study and understood the study's research process and signed the informed consent. Exclusion Criteria: 1.New York Heart Association (NYHA) Class II or greater heart failure; 2.Severe heart disease or discomfort, including but not limited to: High-risk uncontrolled arrhythmias, atrial tachycardia (heart rate>100/min at rest), significant ventricular arrhythmias (ventricular arrhythmias) or higher, atrioventricular block ([Mobitz 2] or third-degree atrioventricular block); Angina pectoris that needs to be treated with anti-anginal medicine; Valvular heart disease with clinical significance; Electrocardiogram shows transmural myocardial infarction; Uncontrolled high blood pressure(eg: Systolic blood pressure> 180 mmHg or diastolic blood pressure> 100 mmHg); 3.Prior received neoadjuvant chemotherapy; 4.Severe systemic infection or other serious disease; 5.Allergies to chemotherapeutic drugs or their excipients or intolerant patients; 6.Other malignant tumors have been found in the past 5 years,except for cured cervical carcinoma in situ, non melanoma of the skin; 7.Childbearing age patients who are pregnant or lactation and refusing to take effective contraceptive measures during the trial; 8.Received any other test drug treatment or participated in other clinical trials at the same time; 9.Other conditions considered to be inappropriate to be enrolled by the investigator.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PLD plus CTX sequential docetaxel or PTX<br>pegylated liposomal doxorubicin 35 mg/m2,i.v.,d1, plus cyclophosphamide（CTX） 600 mg/m2,i.v.,d1, sequential docetaxel 100 mg/m2,i.v.,d1, or paclitaxel（PTX） 80mg/m2,i.v.,d1,8,15, once every 21days, for 4 cycles. | Drug: PLD<br>* pegylated liposomal doxorubicin is 35 mg/m2 intravenously on Days 1 of each 21-day cycle followed by cyclophosphamide.<br>* Other names: duomeisu;Drug: CTX<br>* cyclophosphamide is 600 mg/m2 intravenously on Days 1 of each 21-day cycle, followed by docetaxel or paclitaxel.<br>* Other names: huanlinxianan;Drug: Docetaxel<br>* docetaxel is 100 mg/m2 intravenously on Days 1 of each 21-day cycle.<br>* Other names: taisudi;Drug: Paclitaxel<br>* paclitaxel is 80mg/m2 intravenously on Days 1, 8 and 15 of each 21-day cycle.<br>* Other names: taisu;|
| Active Comparator: DOX plus CTX sequential docetaxel or PTX<br>doxorubicin（DOX） 60 mg/m2,i.v.,d1, plus cyclophosphamide 600 mg/m2,i.v.,d1, sequential docetaxel 100 mg/m2,i.v.,d1, or paclitaxel 80mg/m2,i.v.,d1,8,15, once every 21days, for 4 cycles. | Drug: CTX<br>* cyclophosphamide is 600 mg/m2 intravenously on Days 1 of each 21-day cycle, followed by docetaxel or paclitaxel.<br>* Other names: huanlinxianan;Drug: Docetaxel<br>* docetaxel is 100 mg/m2 intravenously on Days 1 of each 21-day cycle.<br>* Other names: taisudi;Drug: Paclitaxel<br>* paclitaxel is 80mg/m2 intravenously on Days 1, 8 and 15 of each 21-day cycle.<br>* Other names: taisu;Drug: Doxorubicin<br>* doxorubicin is 60 mg/m2 intravenously on Days 1 of each 21-day cycle followed by cyclophosphamide.<br>* Other names: ameisu;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cardiotoxity | Congestive heart failure with clinical symptoms, or no symptoms but an abnormal LVEF | 2 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 5-year DFS | 5-year disease-free survival rate | 5 years | 
| 5-year OS | 5-year overall survival rate | 5 years | 
| Adverse events (AE) | Incidence and Severity of adverse events according to the CTC AE V4.03 | 5 years |