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 (easy laugh)

Shanghai Pudong Hospital

Status: Enrolling

Conditions: Breast Cancer

Treatments: Drug: Pertuzumab; Drug: Epirubicin; Drug: Trastuzumab; Drug: Cyclophosphamid; Drug: Docetaxel; Drug: Pegylated liposomal doxorubicin

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05656079

kazuma

Details and patient eligibility

About

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.

Enrollment: 204 estimated patients

Sex: Female

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. 18-70 years old, Female;
2. Subjects with histopathologically confirmed invasive breast cancer;
3. HER2-positive breast cancer (Immunohistochemistry score of 3+ or fluorescence in situ hybridization positivity);
4. No distant metastasis;
5. Lymph node positive or negative, primary tumour≥2cm;
6. 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;
7. Surgery was completed and chemotherapy was started within 8 weeks after surgery;
8. Before and after chemotherapy LVEF≥55%;
9. ECOG performance status of 0-1;
10. Signed the informed consent.

Exclusion criteria

1. Subjects who are known to be allergic or intolerant to chemotherapy drugs or their excipients;
2. 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);
3. For breast cancer, have received any anti-tumor therapy before randomization (except surgical treatment before enrollment);
4. 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;
5. Have a history of cardiovascular disease or associated with severe cardiovascular disease, lung disease;
6. Active hypertension: systolic blood pressure ≥ 180mmHg, diastolic blood pressure ≥ 90mmHg;
7. NYHA cardiac insufficiency grading ≥ Ⅲ grade;
8. Severe, uncontrollable systemic disease;
9. Subjects who are pregnant or breastfeeding, or subjects who cannot ensure effective contraceptive measures during the study treatment;
10. Subjects who participated in other clinical trials at the same time;
11. Subjects determined by the investigator to be inappropriate to participate in this study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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204 participants in 2 patient groups

pegylated liposomal doxorubicin；cyclophosphamide；trastuzumab；pertuzumab ；docetaxel

Experimental group

Description:

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.

Treatment:

Drug: Pegylated liposomal doxorubicin

Drug: Docetaxel

Drug: Cyclophosphamid

Drug: Trastuzumab

Drug: Pertuzumab

Epirubicin；cyclophosphamide f；docetaxel；trastuzumab；pertuzumab

Active Comparator group

Description:

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.

Treatment:

Drug: Docetaxel

Drug: Cyclophosphamid

Drug: Trastuzumab

Drug: Epirubicin

Drug: Pertuzumab