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
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 204
- Locations
- 1
- Primary Endpoint
- 1-year incidence of cardiotoxicity
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
pegylated liposomal doxorubicin；cyclophosphamide；trastuzumab；pertuzumab ；docetaxel
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.
Intervention: Pegylated liposomal doxorubicin (Drug)
pegylated liposomal doxorubicin；cyclophosphamide；trastuzumab；pertuzumab ；docetaxel
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.
Intervention: Cyclophosphamid (Drug)
pegylated liposomal doxorubicin；cyclophosphamide；trastuzumab；pertuzumab ；docetaxel
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.
Intervention: Trastuzumab (Drug)
pegylated liposomal doxorubicin；cyclophosphamide；trastuzumab；pertuzumab ；docetaxel
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.
Intervention: Pertuzumab (Drug)
pegylated liposomal doxorubicin；cyclophosphamide；trastuzumab；pertuzumab ；docetaxel
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.
Intervention: Docetaxel (Drug)
Epirubicin；cyclophosphamide f；docetaxel；trastuzumab；pertuzumab
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.
Intervention: Epirubicin (Drug)
Epirubicin；cyclophosphamide f；docetaxel；trastuzumab；pertuzumab
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.
Intervention: Cyclophosphamid (Drug)
Epirubicin；cyclophosphamide f；docetaxel；trastuzumab；pertuzumab
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.
Intervention: Trastuzumab (Drug)
Epirubicin；cyclophosphamide f；docetaxel；trastuzumab；pertuzumab
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.
Intervention: Pertuzumab (Drug)
Epirubicin；cyclophosphamide f；docetaxel；trastuzumab；pertuzumab
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.
Intervention: Docetaxel (Drug)
Outcomes
Primary Outcomes
1-year incidence of cardiotoxicity
Time Frame: 1-year
Secondary Outcomes
No secondary outcomes reported