Clinical trial NCT03949634: Cardiac Safety and Efficacy for Early-stage Breast Cancer Patients Treated With Pegylated Liposomal Doxorubicin（PLD)
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Early Breast Cancer
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2019-05-14
Enrollment: 272
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: cardiotoxity
timeFrame: 2 years.
Secondary outcomes:
measure: 5-year DFS
timeFrame: 5 years
measure: 5-year OS
timeFrame: 5 years
measure: Adverse events (AE)
timeFrame: 5 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University affiliated cancer hospital
Study officials:
affiliation: Fudan University affiliated cancer hospital
name: zhimin shao, doctor
role: PRINCIPAL_INVESTIGATOR
References: