EC-THP Versus TCbHP in HER2-positive Lymph Node Positive Early Breast Cancer

Sponsor

Fudan University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05883852

Collaborator

(none)

1,406

Enrollment

Location

Arms

96.8

Anticipated Duration (Months)

14.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

compare the efficacy and safety of TCbHP and EC-THP regimen in HER2-positive breast cancer patients

Condition or Disease	Intervention/Treatment	Phase
HER2 Positive Early Breast Cancer	Drug: Docetaxel Drug: carboplatin Drug: Trastuzumab Drug: Pertuzumab Drug: Epirubicin Drug: cyclophosphamide	Phase 3

Detailed Description

The objective of this study is to conduct a randomized controlled clinical study to compare the efficacy and safety of TCbHP and EC-THP regimen in HER2-positive breast cancer patients, so as to further optimize adjuvant chemotherapy regimen for breast cancer.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1406 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Controlled, Phase III Trial in HER2-positive Lymph Node Positive Early Breast Cancer to Compare the Efficacy and Safety of Epriubin Plus Cyclophosphamide Followed by Docetaxel Plus Trastuzumab and Pertuzumab (EC-THP) Versus Docetaxel and Carboplatin Plus Trastuzumab and Pertuzumab (TCbHP) in the Adjuvant Treatment

Actual Study Start Date :

Jun 6, 2023

Anticipated Primary Completion Date :

Jul 1, 2031

Anticipated Study Completion Date :

Jul 1, 2031

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A：TCbHP Docetaxel 75mg/m2 ivgtt d1+ carboplatin AUC=6 ivgtt d1+ trastuzumab first dose 8mg/kg (maintain 6mg/kg) d1 ivgtt d1+ Pertuzumab first dose 840mg (maintain 420mg) ivgtt d1, 3 weeks of treatment, a total of 6 courses. After the completion of chemotherapy, the dual-target therapy was continued for one year.	Drug: Docetaxel Docetaxel is a taxoid antineoplastic agent used in the treatment of breast cancer Drug: carboplatin Carboplatin is a DNA synthesis inhibitor which binds to DNA, inhibits replication and transcription and induces cell death. Drug: Trastuzumab Trastuzumab is a humanized monoclonal antibody derived from recombinant DNA, Drug: Pertuzumab Pertuzumab is a recombinant humanized monoclonal antibody that specifically binds to the extracellular dimerization domain (subdomain Ⅱ) of epidermal growth factor receptor 2(HER2).
Active Comparator: Arm B：EC-THP Epirubicin 90 mg/m2 ivgtt d1+ cyclophosphamide 600 mg/m2 iv d1, 3 weeks of treatment, a total of 4 courses; Docetaxel 100mg/m2 ivgtt d1+ trastuzumab first dose 8mg/kg (maintenance 6mg/kg) d1 ivgtt d1+ pertuzumab first dose 840mg (maintenance 420mg) ivgtt d1, 3 weeks of treatment, a total of 6 courses. After the completion of chemotherapy, the dual-target therapy was continued for one year.	Drug: Docetaxel Docetaxel is a taxoid antineoplastic agent used in the treatment of breast cancer Drug: Trastuzumab Trastuzumab is a humanized monoclonal antibody derived from recombinant DNA, Drug: Pertuzumab Pertuzumab is a recombinant humanized monoclonal antibody that specifically binds to the extracellular dimerization domain (subdomain Ⅱ) of epidermal growth factor receptor 2(HER2). Drug: Epirubicin Epirubicin is an antineoplastic agent derived from doxorubicin.Epirubicin, like doxorubicin, exerts its antitumor effects by interference with the synthesis and function of DNA and is most active during the S phase of the cell cycle. Drug: cyclophosphamide An anticancer (antitumor or cytotoxic) chemotherapy drug that is classified as an alkylating agent. Alkylating agents are compounds that prevent the normal connection of the double helix chain by adding an alkyl group to the guanine base of the DNA molecule. It causes breaks in DNA strands, affecting the ability of cancer cells to proliferate.

Arm

Intervention/Treatment

Experimental: Arm A：TCbHP

Docetaxel 75mg/m2 ivgtt d1+ carboplatin AUC=6 ivgtt d1+ trastuzumab first dose 8mg/kg (maintain 6mg/kg) d1 ivgtt d1+ Pertuzumab first dose 840mg (maintain 420mg) ivgtt d1, 3 weeks of treatment, a total of 6 courses. After the completion of chemotherapy, the dual-target therapy was continued for one year.

Drug: Docetaxel

Docetaxel is a taxoid antineoplastic agent used in the treatment of breast cancer

Drug: carboplatin

Carboplatin is a DNA synthesis inhibitor which binds to DNA, inhibits replication and transcription and induces cell death.

Drug: Trastuzumab

Trastuzumab is a humanized monoclonal antibody derived from recombinant DNA,

Drug: Pertuzumab

Pertuzumab is a recombinant humanized monoclonal antibody that specifically binds to the extracellular dimerization domain (subdomain Ⅱ) of epidermal growth factor receptor 2(HER2).

Active Comparator: Arm B：EC-THP

Epirubicin 90 mg/m2 ivgtt d1+ cyclophosphamide 600 mg/m2 iv d1, 3 weeks of treatment, a total of 4 courses; Docetaxel 100mg/m2 ivgtt d1+ trastuzumab first dose 8mg/kg (maintenance 6mg/kg) d1 ivgtt d1+ pertuzumab first dose 840mg (maintenance 420mg) ivgtt d1, 3 weeks of treatment, a total of 6 courses. After the completion of chemotherapy, the dual-target therapy was continued for one year.

Drug: Docetaxel

Docetaxel is a taxoid antineoplastic agent used in the treatment of breast cancer

Drug: Trastuzumab

Trastuzumab is a humanized monoclonal antibody derived from recombinant DNA,

Drug: Pertuzumab

Pertuzumab is a recombinant humanized monoclonal antibody that specifically binds to the extracellular dimerization domain (subdomain Ⅱ) of epidermal growth factor receptor 2(HER2).

Drug: Epirubicin

Epirubicin is an antineoplastic agent derived from doxorubicin.Epirubicin, like doxorubicin, exerts its antitumor effects by interference with the synthesis and function of DNA and is most active during the S phase of the cell cycle.

Drug: cyclophosphamide

An anticancer (antitumor or cytotoxic) chemotherapy drug that is classified as an alkylating agent. Alkylating agents are compounds that prevent the normal connection of the double helix chain by adding an alkyl group to the guanine base of the DNA molecule. It causes breaks in DNA strands, affecting the ability of cancer cells to proliferate.

Outcome Measures

Primary Outcome Measures

iDFS [5 years]
invasive Disease Free Survival

Secondary Outcome Measures

DRFS [5 years]
distant relapse free survival
OS [5 years]
overall survival
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [through study completion, an average of 1 year]
Incidence of treatment-emergent adverse events adverse events according to CTCAE 5.0

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Women aged 18-70；
0-1 for ECOG；
Unilateral invasive carcinoma confirmed by histology (regardless of pathological type)；
No gross or microscopic tumor remains after surgical resection；
Early breast cancer, pathologically confirmed as HER2 positive; HER2 positive definition: Immunohistochemical HER2 3+ or FISH/CISH test positive (with amplification) is defined as HER2 positive；
Postoperative pathological stage pT1-4N1-3M0；
Did not receive neoadjuvant chemotherapy in the past；
The longest period from surgery to randomization was not more than 8 weeks, and no adjuvant therapy had been received after surgery；
No peripheral neuropathy；
Good postoperative recovery, at least 1 week interval between operation；
The major organs function normally, that is, meet the following criteria: (1) The standard of blood routine examination shall meet: HB ≥90 g/L (no blood transfusion within 14 days); ANC ≥1.5×109 /L; PLT ≥100×109 /L; (2) Biochemical examination should meet the following standards: TBIL ≤1.5×ULN (upper limit of normal value); ALT and AST ≤3 x ULN; Serum Cr ≤1.5×ULN；
Contraception during treatment for women of reproductive age；
Cardiac function: LVEF>50% for ultrasound examination；
The subjects voluntarily joined the study, signed the informed consent, had good compliance, and cooperated with follow-up。

Exclusion Criteria:

Bilateral breast cancer or carcinoma in situ DCIS/LCIS；
Have received chemotherapy for advanced disease；
Transfer of any part；
If any tumor >T4a (accompanied by skin invasion, mass adhesion fixation, inflammatory breast cancer)；
Patients with clinical or imaging suspicion of malignancy on the opposite breast but not confirmed, requiring biopsy；
Have received neoadjuvant therapy, including chemotherapy, radiotherapy and endocrine therapy；
Malignant neoplasms (other than basal cell carcinoma of the skin and carcinoma in situ of the cervix), including contralateral breast cancer, within the previous 5 years；
The patient has been enrolled in other clinical trials；
Patients with severe systemic disease and/or uncontrolled infection were unable to be enrolled in the study；
LVEF<50% (cardiac ultrasound)；
Severe cardiovascular and cerebrovascular disease (e.g., unstable angina, chronic heart failure, uncontrolled hypertension >150/90mmgh, myocardial infarction or cerebrovascular accident) within 6 months prior to randomization；
Known allergy to related drugs；
Women of childbearing age refuse contraception during treatment and within 8 weeks after completion of treatment；
Pregnant and lactating women；
Those who tested positive for pregnancy before taking the drug after joining the trial；
Mental illness, cognitive impairment, inability to understand the trial protocol and side effects, inability to complete the trial protocol and follow-up workers ；(systematic evaluation is required before trial enrollment)；
Persons without personal freedom and independent capacity for civil conduct。