To Evaluate the Cardiac Safety of Pegylated Liposomal Doxorubicin Concurrently Plus Trastuzumab and Pertuzumab in the Adjuvant Setting for Early-stage HER-2-positive Breast Cancer: a Multicenter, Randomized Controlled Clinical Study

Study Overview
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Brief Summary
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To evaluate the safety and efficacy of pegylated liposomal doxorubicin/cyclophosphamide/trastuzumab/pertuzumab followed by docetaxel/ trastuzumab/pertuzumab compared with epirubicin/cyclophosphamide followed by docetaxel/trastuzumab/pertuzumab in the adjuvant treatment of early breast cancer.

Official Title
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To Evaluate the Cardiac Safety of Pegylated Liposomal Doxorubicin Concurrently Plus Trastuzumab and Pertuzumab in the Adjuvant Setting for Early-stage HER-2-positive Breast Cancer: a Multicenter, Randomized Controlled Clinical Study

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Pegylated liposomal doxorubicin
* Drug: Epirubicin
* Drug: Cyclophosphamid
* Drug: Trastuzumab
* Drug: Pertuzumab
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-70 years old, Female; Subjects with histopathologically confirmed invasive breast cancer; HER2-positive breast cancer (Immunohistochemistry score of 3+ or fluorescence in situ hybridization positivity); No distant metastasis; Lymph node positive or negative, primary tumour≥2cm; Lymph node negative，primary tumour≤2cm and any of the following factors; 1) Histological grade 3; 2) ER negative (<10%) and PR negative (<20%); 3) Age<35 years old; 4) Pathological hint: vascular invasion or intravascular cancer thrombus; Surgery was completed and chemotherapy was started within 8 weeks after surgery; Before and after chemotherapy LVEF≥55%; ECOG performance status of 0-1; Signed the informed consent. Exclusion Criteria: Subjects who are known to be allergic or intolerant to chemotherapy drugs or their excipients; Previously suffered from invasive breast cancer, and other malignant tumors within 5 years (excluding carcinoma in situ of the cervix, carcinoma in situ of the rectum, carcinoma in situ of melanoma, basal cell carcinoma of the skin, and squamous cell carcinoma); For breast cancer, have received any anti-tumor therapy before randomization (except surgical treatment before enrollment); Hematopoietic function, renal function and liver function meet one of the following conditions: 1) Neutrophil count ≤1.5×109/L; 2) Platelet count ≤ 50×109/L; 3) Hemoglobin ≤ 8.0g/dL; 4) Creatinine clearance rate ≤30ml/min; 5) AST and ALT ≥ 2.5 times the upper limit of normal in subjects without liver metastases; 6) Bilirubin ≥ 2 times the upper limit of normal; 7) APTT/PT≥1.5 times the upper limit of normal; Have a history of cardiovascular disease or associated with severe cardiovascular disease, lung disease; Active hypertension: systolic blood pressure ≥ 180mmHg, diastolic blood pressure ≥ 90mmHg; NYHA cardiac insufficiency grading ≥ Ⅲ grade; Severe, uncontrollable systemic disease; Subjects who are pregnant or breastfeeding, or subjects who cannot ensure effective contraceptive measures during the study treatment; Subjects who participated in other clinical trials at the same time; Subjects determined by the investigator to be inappropriate to participate in this 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: pegylated liposomal doxorubicin；cyclophosphamide；trastuzumab；pertuzumab ；docetaxel<br>Pegylated liposomal doxorubicin 35 mg/m2, i.v. d1 +Cyclophosphamide 600 mg/m2 , i.v. d1 +Trastuzumab (8 mg/kg loading dose at first day only, then 6 mg/kg), i.v. d1+Pertuzumab (840 mg loading dose at first day only, then 420 mg), i.v. d1 ； q3w, for 4 cycles followed by Docetaxel 75mg/m2 , i.v. d1+ Pertuzumab 420 mg, i.v. d1+Trastuzumab 6 mg/kg, i.v. d1； q3w, for 4 cycles. After the completion of adjuvant therapy, patients are required to receive a total of 1 year of treatment with trastuzumab combined with pertuzumab. | Drug: Pegylated liposomal doxorubicin<br>* Drug: Pegylated liposomal doxorubicin (35 mg/m2) will be administered by an intravenous infusion on day 1 of each21-day cycle.<br>* Other names: Doxorubicin Hydrochloride Liposome Injection;Drug: Cyclophosphamid<br>* Drug: Cyclophosphamide (600 mg/m2) will be administered by an intravenous infusion on day 1 of each 21-day cycle.<br>* Other names: huanlinxianan;Drug: Trastuzumab<br>* Drug: Trastuzumab (8 mg/kg loading dose at first day only, then 6 mg/kg) will be administered by an intravenous infusion on day 1 of each 21-day cycle.<br>* Other names: qutuozhudankang;Drug: Pertuzumab<br>* Drug: Pertuzumab (840 mg loading dose at first day only, then 420 mg) will be administered by an intravenous infusion on day 1 of each 21-day cycle.<br>* Other names: patuozhudankang;Drug: Docetaxel<br>* Drug: Docetaxel (75mg/m2) will be administered by an intravenous infusion on day 1 of each 21-day cycle.<br>* Other names: duoxitasai;|
| Active Comparator: Epirubicin；cyclophosphamide f；docetaxel；trastuzumab；pertuzumab<br>Epirubicin 90 mg/m2 , i.v. d1 +Cyclophosphamide 600 mg/m2 , i.v. d1； q3w, for 4 cycles followed by Docetaxel 75mg/m2 , i.v. d1+Trastuzumab (8 mg/kg loading dose at first day only, then 6 mg/kg), i.v. d1+Pertuzumab (840 mg loading dose at first day only, then 420 mg), i.v. d1； q3w, for 4 cycles. After the completion of adjuvant therapy, patients are required to receive a total of 1 year of treatment with trastuzumab combined with pertuzumab. | Drug: Epirubicin<br>* Drug: Epirubicin (90 mg/m2) will be administered by an intravenous infusion on day 1 of each 21-day cycle.<br>* Other names: biaoroubixing;Drug: Cyclophosphamid<br>* Drug: Cyclophosphamide (600 mg/m2) will be administered by an intravenous infusion on day 1 of each 21-day cycle.<br>* Other names: huanlinxianan;Drug: Trastuzumab<br>* Drug: Trastuzumab (8 mg/kg loading dose at first day only, then 6 mg/kg) will be administered by an intravenous infusion on day 1 of each 21-day cycle.<br>* Other names: qutuozhudankang;Drug: Pertuzumab<br>* Drug: Pertuzumab (840 mg loading dose at first day only, then 420 mg) will be administered by an intravenous infusion on day 1 of each 21-day cycle.<br>* Other names: patuozhudankang;Drug: Docetaxel<br>* Drug: Docetaxel (75mg/m2) will be administered by an intravenous infusion on day 1 of each 21-day cycle.<br>* Other names: duoxitasai;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year incidence of cardiotoxicity |  | 1-year |