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A Multicenter, Randomized, Open, Phase III Trial of ddEC-THPvs Evaluating the Efficacy and Safety of TCHP Neoadjuvant Therapy for HER2-positive Breast Cancer

Primary Purpose

HER-2 Positive Breast Cancer

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
TCbHP VS ddEC-THP
Sponsored by
Tianjin Medical University Cancer Institute and Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HER-2 Positive Breast Cancer

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: Age: 18 ~70 years old, female; Histologically confirmed patients with previously untreated stage Ⅱ-Ⅲ HER2-positive breast cancer; HER-2 positive breast cancer, defined as immunohistochemical (IHC) detection of 3+ or in situ hybridization (FISH) results of HER2 gene amplification; There is at least one measurable objective lesion according to RECIST 1.1 criteria; ECOG Physical fitness score is 0-2; Left ventricular ejection fraction LVEF≥50%; Bone marrow function: neutrophils ≥1.5×109/L, platelets ≥100×109/L, hemoglobin ≥90g/L; Liver and kidney function: serum creatinine ≤1.5 times the upper limit of normal value; AST and ALT≤2.5 times the upper limit of normal, or ≤5 times the upper limit of normal in the presence of liver metastasis; Total bilirubin ≤1.5 times the upper limit of normal, or ≤2.5 times the upper limit of normal in patients with Gilbert's syndrome, creatinine clearance greater than 30 mL/min; For female patients who are not menopausal or have not been surgically sterilized: consent to abstinence or use an effective contraceptive method during treatment and for at least 7 months after the last dose in the study treatment The patient has good compliance with the planned treatment, can understand the research process of the study and sign the written informed consent. Exclusion Criteria: Stage IV (metastatic) breast cancer patients; Patients with inflammatory breast cancer Serious heart disease or discomfort, including but not limited to: History of heart failure or systolic dysfunction (LVEF < 50%) High-risk uncontrolled arrhythmias such as atrial tachycardia, resting heart rate > 100 bpm, significant ventricular arrhythmias (e.g., ventricular tachycardia) or higher-grade atrioventricular block (i.e., Mobitz II second-degree atrioventricular block or third-degree atrioventricular block) Angina pectoris that requires antiangina medication valvular heart disease of clinical significance ECG showed transmural myocardial infarction Poor hypertension control (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg) Known allergic history of drug components of this protocol; A history of immunodeficiency, including HIV positive, or other acquired, congenital immunodeficiency diseases, or a history of organ transplantation; Patients with severe systemic infection or accompanied by other serious diseases; Have developed other malignant tumors within the previous 5 years, except for cured cervical carcinoma in situ and non-melanoma skin cancer; Pregnant and lactating women, fertile women who tested positive for baseline pregnancy tests, or patients of childbearing age who were unwilling to take effective contraceptive measures during the entire trial period and within 6 months after the last study; Patients who participated in other studies within 30 days prior to the first dose of the investigational drug; Patients deemed unsuitable for this study by the investigator. The patient has good compliance with the planned treatment, can understand the research process of the study and sign the written informed consent.

Sites / Locations

  • Breast Oncology, Tianjin Medical University Cancer Institute and HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

TCbHP

ddEC-THP

Arm Description

Experimental group (TCbHP) : Taxotere (75mg/m2) + Carboplatin (AUC=5) Trastuzumab 6mg/kg(initial dose 8mg/kg) Pertuzumab 420mg(initial dose 840mg) 1/21d times 6 cycle

Epirubicin (90mg/m2)+ cyclophosphamide (600mg/m2) 1/14d×4 cycle Taxol (80mg/m2) 1/7d x 12w Trastuzumab 6mg/kg(initial dose 8mg/kg) 1/21d ×4 cycles Pertuzumab 420mg(initial dose 840mg) 1/21d x 4 cycles

Outcomes

Primary Outcome Measures

pCR rate using the definition of ypT0/Tis ypN0 (i.e., no invasive residual in breast or nodes; noninvasive breast residuals allowed) at the time of definitive surgery
pCR rate (ypT0/is,ypN0) is defined as the percentage of participants without residual invasive tumor on hematoxylin and eosin evaluation of breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by current AJCC staging criteria assessed by the local pathologist at the time of definitive surgery in all participants.

Secondary Outcome Measures

Event-Free Survival (EFS)
EFS is defined as the time from start of study treatment to any of the following events: progression of disease that precludes surgery, local or distant recurrence, second primary malignancy (breast or other cancers) or death due to any cause.
Invasive Disease-Free Survival (iDFS)
iDFS events are defined as follows: (1)Ipsilateral invasive breast tumor recurrence. (2) Ipsilateral local-regional invasive breast cancer recurrence. (3) Ipsilateral second primary invasive breast cancer. (4) Contralateral invasive breast cancer. (5) Distant recurrence. (6) Death attributable to any cause.
Overall survival (OS)
OS is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis will be censored at the date of the last follow-up.

Full Information

First Posted
May 15, 2023
Last Updated
May 15, 2023
Sponsor
Tianjin Medical University Cancer Institute and Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05871918
Brief Title
A Multicenter, Randomized, Open, Phase III Trial of ddEC-THPvs Evaluating the Efficacy and Safety of TCHP Neoadjuvant Therapy for HER2-positive Breast Cancer
Official Title
A Multicenter, Randomized, Open, Phase III Trial of ddEC-THP(Epirubicin,Cyclophosphamide,TAX(Taxol),Trastuzumab,Pertuzumab)vs Evaluating the Efficacy and Safety of TCHP (CBP(Carboplatin),TXT(Taxotere),Trastuzumab,Pertuzumab)Neoadjuvant Therapy for HER2-positive Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 8, 2022 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tianjin Medical University Cancer Institute and Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The study is being conducted to assess the efficacy and safety of anthracycline-containing ddEC-THP intensive regimen and an anthracycline-free TCbHP neoadjuvant therapy for HER2-positive breast cancer
Detailed Description
A Multicenter, Randomized, Open, Phase III,The study is being conducted to assess the efficacy and safety of anthracycline-containing ddEC-THP intensive regimen and an anthracycline-free TCbHP neoadjuvant therapy for HER2-positive breast cancer,Subjects will be treated until disease progression, toxicity is intolerable, informed consent is withdrawn, and investigators determine that medication must be discontinued. Drug efficacy and safety data will be collected.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HER-2 Positive Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
832 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TCbHP
Arm Type
Experimental
Arm Description
Experimental group (TCbHP) : Taxotere (75mg/m2) + Carboplatin (AUC=5) Trastuzumab 6mg/kg(initial dose 8mg/kg) Pertuzumab 420mg(initial dose 840mg) 1/21d times 6 cycle
Arm Title
ddEC-THP
Arm Type
Placebo Comparator
Arm Description
Epirubicin (90mg/m2)+ cyclophosphamide (600mg/m2) 1/14d×4 cycle Taxol (80mg/m2) 1/7d x 12w Trastuzumab 6mg/kg(initial dose 8mg/kg) 1/21d ×4 cycles Pertuzumab 420mg(initial dose 840mg) 1/21d x 4 cycles
Intervention Type
Drug
Intervention Name(s)
TCbHP VS ddEC-THP
Intervention Description
The efficacy was evaluated every two cycles, and the effective patients (CR, PR, SD) were treated with surgery after 6 cycles. If treatment does not work, change the treatment plan according to the clinician's decision.
Primary Outcome Measure Information:
Title
pCR rate using the definition of ypT0/Tis ypN0 (i.e., no invasive residual in breast or nodes; noninvasive breast residuals allowed) at the time of definitive surgery
Description
pCR rate (ypT0/is,ypN0) is defined as the percentage of participants without residual invasive tumor on hematoxylin and eosin evaluation of breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by current AJCC staging criteria assessed by the local pathologist at the time of definitive surgery in all participants.
Time Frame
Up to approximately 24 weeks
Secondary Outcome Measure Information:
Title
Event-Free Survival (EFS)
Description
EFS is defined as the time from start of study treatment to any of the following events: progression of disease that precludes surgery, local or distant recurrence, second primary malignancy (breast or other cancers) or death due to any cause.
Time Frame
Up to approximately 3 years
Title
Invasive Disease-Free Survival (iDFS)
Description
iDFS events are defined as follows: (1)Ipsilateral invasive breast tumor recurrence. (2) Ipsilateral local-regional invasive breast cancer recurrence. (3) Ipsilateral second primary invasive breast cancer. (4) Contralateral invasive breast cancer. (5) Distant recurrence. (6) Death attributable to any cause.
Time Frame
Up to approximately 3 years
Title
Overall survival (OS)
Description
OS is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis will be censored at the date of the last follow-up.
Time Frame
Up to approximately 3 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age: 18 ~70 years old, female; Histologically confirmed patients with previously untreated stage Ⅱ-Ⅲ HER2-positive breast cancer; HER-2 positive breast cancer, defined as immunohistochemical (IHC) detection of 3+ or in situ hybridization (FISH) results of HER2 gene amplification; There is at least one measurable objective lesion according to RECIST 1.1 criteria; ECOG Physical fitness score is 0-2; Left ventricular ejection fraction LVEF≥50%; Bone marrow function: neutrophils ≥1.5×109/L, platelets ≥100×109/L, hemoglobin ≥90g/L; Liver and kidney function: serum creatinine ≤1.5 times the upper limit of normal value; AST and ALT≤2.5 times the upper limit of normal, or ≤5 times the upper limit of normal in the presence of liver metastasis; Total bilirubin ≤1.5 times the upper limit of normal, or ≤2.5 times the upper limit of normal in patients with Gilbert's syndrome, creatinine clearance greater than 30 mL/min; For female patients who are not menopausal or have not been surgically sterilized: consent to abstinence or use an effective contraceptive method during treatment and for at least 7 months after the last dose in the study treatment The patient has good compliance with the planned treatment, can understand the research process of the study and sign the written informed consent. Exclusion Criteria: Stage IV (metastatic) breast cancer patients; Patients with inflammatory breast cancer Serious heart disease or discomfort, including but not limited to: History of heart failure or systolic dysfunction (LVEF < 50%) High-risk uncontrolled arrhythmias such as atrial tachycardia, resting heart rate > 100 bpm, significant ventricular arrhythmias (e.g., ventricular tachycardia) or higher-grade atrioventricular block (i.e., Mobitz II second-degree atrioventricular block or third-degree atrioventricular block) Angina pectoris that requires antiangina medication valvular heart disease of clinical significance ECG showed transmural myocardial infarction Poor hypertension control (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg) Known allergic history of drug components of this protocol; A history of immunodeficiency, including HIV positive, or other acquired, congenital immunodeficiency diseases, or a history of organ transplantation; Patients with severe systemic infection or accompanied by other serious diseases; Have developed other malignant tumors within the previous 5 years, except for cured cervical carcinoma in situ and non-melanoma skin cancer; Pregnant and lactating women, fertile women who tested positive for baseline pregnancy tests, or patients of childbearing age who were unwilling to take effective contraceptive measures during the entire trial period and within 6 months after the last study; Patients who participated in other studies within 30 days prior to the first dose of the investigational drug; Patients deemed unsuitable for this study by the investigator. The patient has good compliance with the planned treatment, can understand the research process of the study and sign the written informed consent.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhongsheng Tong
Phone
+8618622221181
Email
18622221181@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Lin Gu
Phone
+8613011309052
Email
gulindr@126.com
Facility Information:
Facility Name
Breast Oncology, Tianjin Medical University Cancer Institute and Hospital
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300060
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhongsheng Tong, MD
Phone
+8618622221181
Email
18622221181@163.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Multicenter, Randomized, Open, Phase III Trial of ddEC-THPvs Evaluating the Efficacy and Safety of TCHP Neoadjuvant Therapy for HER2-positive Breast Cancer

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