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TCb vs EC-T in High Risk ER+/HER2- Breast Cancer

Primary Purpose

Hormone Receptor Positive HER-2 Negative Breast Cancer

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Docetaxel
Carboplatin
Epirubicin
Cyclophosphamide
Sponsored by
Fudan University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hormone Receptor Positive HER-2 Negative Breast Cancer focused on measuring LN≥4, TCb, EC-T

Eligibility Criteria

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

Inclusion Criteria: Women aged 18-70 Unilateral invasive carcinoma confirmed by histology (regardless of pathological type) The initial diagnosis condition can be directly operated, without absolute surgical contraindications No gross or microscopic tumor remains after surgical resection Adjuvant chemotherapy should be started within eight weeks after surgery Patients with Hormone receptor-positive, HER2-negative (HR+HER2-), and positive axillary lymph nodes ≥4 Definition of ER and Progesterone Receptor (PgR) positive: Positive ER for tumor cells detected by immunohistochemistry is defined as ER positive , and positive PgR for tumor cells detected as PgR positive . There was no evidence of metastasis in clinical or imaging aspects during preoperative examination No peripheral neuropathy; Eastern Oncology Collaborative Group (ECOG) physical status score: 0 or 1 Good postoperative recovery, at least 1 week interval between surgery Adequate hematological and end-organ function as defined by the following laboratory test results, which need to be completed within 28 days prior to the first study treatment: absolute neutrophil count (ANC) ≥ 1500 cells/μL (no granulocyte colony stimulating factor (G-CSF) support therapy within 2 weeks prior to day 1 of course 1); Lymphocyte count≥ 500 cells/μL; Platelet count≥ 100,000 cells/μL (no platelet transfusion within 2 weeks before day 1 of course 1; hemoglobin≥ 9.0 g/dL; Aspartate transferase (AST), Alanine aminotransferase (ALT), and alkaline phosphatase≤ 2.5 × upper limit of normal (ULN) serum total bilirubin ≤ 1.0 × ULN; Patients with known Gilbert disease and serum bilirubin levels ≤ 3× ULN may be admitted; For patients not receiving anticoagulant therapy: INR or activated partial thromboplastin time (APTT) ≤ 1.5 × ULN within 28 days prior to initiation of study therapy; For patients receiving anticoagulant therapy: a stable anticoagulant regimen within 28 days before the start of study therapy and a stable International normalised ratio (INR); creatinine clearance≥ 30 mL/min (calculated using the Cockcroft-Gault formula); Serum albumin ≥ 2.5 g/dL For women of childbearing age: agree to remain abstinent (avoid heterosexual intercourse) or take an annual failure rate for at least 5 months during treatment and at least 6 months after the last dose of docetaxel or epirubicin, or 12 months after the last dose of cyclophosphamide, whichever occurs last < 1% of contraception. A woman who is postmenopausal but has not yet reached postmenopausal status (menopause lasts ≥for 12 consecutive months, for no reason other than menopause) and has not undergone sterilization (ovarian and/or hysterectomy) is considered fertile. Cardiac function: left ventricular ejection fraction (LVEF) >50% by ultrasound examination Sign the Informed Consent Form (ICF) Exclusion Criteria: Have a history of invasive cancer T4 clinical tumors as specified in the Union for International Cancer Control/American Joint Committee on Cancer tumor (UICC/AJCC) Tumor-Lymph Node Metastasis Classification (8th Edition), including inflammatory breast cancer For currently diagnosed breast cancer, prior systemic anticancer therapy (eg, neoadjuvant therapy or adjuvant therapy) includes, but is not limited to, chemotherapy, anti-HER2 therapy (eg, trastuzumab emtansine, pertuzumab, lapatinib, neratinib or other tyrosine kinase inhibitors), hormone therapy, or anti-cancer radiotherapy (RT), except for treatments planned under this study condition Previous treatment with anthracyclines or taxane for any malignant tumor History of ductal carcinoma in situ (DCIS) and/or lobular carcinoma in situ (LCIS), treatment of ipsilateral breast cancer with systemic therapy, hormone therapy, or RT, followed by invasive cancer, patients treated with DCIS/LCIS only surgery and/or RT for contralateral DCIS may be enrolled in the study. Prior to randomization, cardiopulmonary dysfunction according to any of the following: history of NCI CTCAE v4.0 ≥3 symptomatic congestive heart failure or New York College of Cardiology (NYHA) standard classification≥ II, angina requiring antianginal drugs, severe arrhythmias not treated with appropriate medical therapy, severe conduction abnormalities, or clinically significant valvular disease, high-risk, uncontrolled arrhythmias (i.e., atrial tachycardia with > resting rate). 100/min, significant ventricular arrhythmia [ventricular tachycardia], or high-grade atrioventricular (AV) block [second-degree AV block type 2, or third-degree atrioventricular block]), significant symptoms associated with left ventricular dysfunction, arrhythmia, or myocardial ischemia (grade ≥2), myocardial infarction within 12 hours prior to randomization; with uncontrolled hypertension (systolic blood pressure> 180 mmHg and/or diastolic blood pressure > 100 mmHg; ECG findings show transmural infarction; Oxygen therapy is required Prior malignancy within 5 years prior to randomization, with negligible risk of metastasis or death, except for malignancy that is expected to heal after treatment (i.e., appropriately treated carcinoma in situ or basal or squamous cell skin cancer). Known allergic or hypersensitivity to any component of the docetaxel, carboplatin, cyclophosphamide, or epirubicin preparations; Allergic or hypersensitivity reactions are known to filgrastim, pegfilgrastim, or granulocyte-macrophage colony-stimulating factor (GM-CSF) preparations Patients with serious infections (including but not limited to hospitalization due to infectious complications, bacteremia, or severe pneumonia) that occurred within 4 weeks prior to initiation of study treatment, who received therapeutic oral or intravenous antibiotics within 2 weeks prior to initiation of study treatment, and who received prophylactic antibiotic therapy (such as prophylaxis for urinary tract infection or prevention of chronic obstructive pulmonary disease) may be enrolled. Pregnant or lactating women, or women planning to become pregnant during the study period. Poorly controlled hypertension (defined as: systolic blood pressure > 150 mmHg and/or diastolic blood pressure >100 mmHg) Mental illness, cognitive impairment, inability to understand the trial protocol and side effects, and 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.

Sites / Locations

  • Breast cancer institute of Fudan University Cancer HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

TCb arm

EC-T arm

Arm Description

Chemotherapy: Intensive intravenous dose of docetaxel (75 mg/m2) + intravenous (IV) carboplatin [area under the curve (AUC) =5-6] repeated administration of Q3W for a total of 6 doses

Chemotherapy: Intensive intravenous dose of epirubicin (80-90 mg/m2) + IV cyclophosphamide (600 mg/m2) repeated administration of Q3W for a total of 4 doses, followed by (IV) docetaxel (80 mg/m2) (Q3W) for 4 doses

Outcomes

Primary Outcome Measures

invasive disease-free survival (iDFS)
invasive disease-free survival

Secondary Outcome Measures

distant relapse free survival (DRFS)
distant relapse free survival
overall survival (OS)
overall survival
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Incidence of treatment-emergent adverse events adverse events according to CTCAE 5.0
Quality of life measured by EORTC QLQ C30
Registration of differences in quality of life between the two groups in the study. EORTC QLQ-C30(scale range 0-100, a higher score indicating better quality of life) will be used for as quality of life measurement. The scores will be presented graphically in separate figures. Differences between the groups will be tested using t-test and analysis of covariance.

Full Information

First Posted
May 7, 2023
Last Updated
June 12, 2023
Sponsor
Fudan University
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1. Study Identification

Unique Protocol Identification Number
NCT05901428
Brief Title
TCb vs EC-T in High Risk ER+/HER2- Breast Cancer
Official Title
A Randomized, Open-label, Single-center, Phase III Trial Comparing Docetaxel Plus Carboplatin (TCb) Versus Epirubicin Plus Cyclophosphamide Followed by Docetaxel (EC-T) Regimen as Adjuvant Chemotherapy in Patients With LN≥4 Estrogen Receptor Positive and Human Epidermal Growth Factor Receptor 2 Negative (ER+/HER2-) Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 1, 2023 (Actual)
Primary Completion Date
June 2026 (Anticipated)
Study Completion Date
June 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fudan University

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
This study will evaluate the efficacy and safety of docetaxel plus carboplatin (TCb) regimen compared with conventional chemotherapy regimen (epirubicin plus cyclophosphamide followed by docetaxel, EC-T) regimen as adjuvant chemotherapy in patients with early-stage high-risk estrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) breast cancer.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hormone Receptor Positive HER-2 Negative Breast Cancer
Keywords
LN≥4, TCb, EC-T

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1736 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TCb arm
Arm Type
Experimental
Arm Description
Chemotherapy: Intensive intravenous dose of docetaxel (75 mg/m2) + intravenous (IV) carboplatin [area under the curve (AUC) =5-6] repeated administration of Q3W for a total of 6 doses
Arm Title
EC-T arm
Arm Type
Active Comparator
Arm Description
Chemotherapy: Intensive intravenous dose of epirubicin (80-90 mg/m2) + IV cyclophosphamide (600 mg/m2) repeated administration of Q3W for a total of 4 doses, followed by (IV) docetaxel (80 mg/m2) (Q3W) for 4 doses
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Intervention Description
Docetaxel is a taxoid antineoplastic agent used in the treatment of breast cancer
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
Carboplatin is a deoxyribonucleic acid (DNA) synthesis inhibitor which binds to DNA, inhibits replication and transcription and induces cell death.
Intervention Type
Drug
Intervention Name(s)
Epirubicin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Cyclophosphamide is a nitrogen mustard that exerts its anti-neoplastic effects through alkylation.
Primary Outcome Measure Information:
Title
invasive disease-free survival (iDFS)
Description
invasive disease-free survival
Time Frame
5 years
Secondary Outcome Measure Information:
Title
distant relapse free survival (DRFS)
Description
distant relapse free survival
Time Frame
5 years
Title
overall survival (OS)
Description
overall survival
Time Frame
5 years
Title
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Description
Incidence of treatment-emergent adverse events adverse events according to CTCAE 5.0
Time Frame
through study completion, an average of 1 year
Title
Quality of life measured by EORTC QLQ C30
Description
Registration of differences in quality of life between the two groups in the study. EORTC QLQ-C30(scale range 0-100, a higher score indicating better quality of life) will be used for as quality of life measurement. The scores will be presented graphically in separate figures. Differences between the groups will be tested using t-test and analysis of covariance.
Time Frame
5 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: Women aged 18-70 Unilateral invasive carcinoma confirmed by histology (regardless of pathological type) The initial diagnosis condition can be directly operated, without absolute surgical contraindications No gross or microscopic tumor remains after surgical resection Adjuvant chemotherapy should be started within eight weeks after surgery Patients with Hormone receptor-positive, HER2-negative (HR+HER2-), and positive axillary lymph nodes ≥4 Definition of ER and Progesterone Receptor (PgR) positive: Positive ER for tumor cells detected by immunohistochemistry is defined as ER positive , and positive PgR for tumor cells detected as PgR positive . There was no evidence of metastasis in clinical or imaging aspects during preoperative examination No peripheral neuropathy; Eastern Oncology Collaborative Group (ECOG) physical status score: 0 or 1 Good postoperative recovery, at least 1 week interval between surgery Adequate hematological and end-organ function as defined by the following laboratory test results, which need to be completed within 28 days prior to the first study treatment: absolute neutrophil count (ANC) ≥ 1500 cells/μL (no granulocyte colony stimulating factor (G-CSF) support therapy within 2 weeks prior to day 1 of course 1); Lymphocyte count≥ 500 cells/μL; Platelet count≥ 100,000 cells/μL (no platelet transfusion within 2 weeks before day 1 of course 1; hemoglobin≥ 9.0 g/dL; Aspartate transferase (AST), Alanine aminotransferase (ALT), and alkaline phosphatase≤ 2.5 × upper limit of normal (ULN) serum total bilirubin ≤ 1.0 × ULN; Patients with known Gilbert disease and serum bilirubin levels ≤ 3× ULN may be admitted; For patients not receiving anticoagulant therapy: INR or activated partial thromboplastin time (APTT) ≤ 1.5 × ULN within 28 days prior to initiation of study therapy; For patients receiving anticoagulant therapy: a stable anticoagulant regimen within 28 days before the start of study therapy and a stable International normalised ratio (INR); creatinine clearance≥ 30 mL/min (calculated using the Cockcroft-Gault formula); Serum albumin ≥ 2.5 g/dL For women of childbearing age: agree to remain abstinent (avoid heterosexual intercourse) or take an annual failure rate for at least 5 months during treatment and at least 6 months after the last dose of docetaxel or epirubicin, or 12 months after the last dose of cyclophosphamide, whichever occurs last < 1% of contraception. A woman who is postmenopausal but has not yet reached postmenopausal status (menopause lasts ≥for 12 consecutive months, for no reason other than menopause) and has not undergone sterilization (ovarian and/or hysterectomy) is considered fertile. Cardiac function: left ventricular ejection fraction (LVEF) >50% by ultrasound examination Sign the Informed Consent Form (ICF) Exclusion Criteria: Have a history of invasive cancer T4 clinical tumors as specified in the Union for International Cancer Control/American Joint Committee on Cancer tumor (UICC/AJCC) Tumor-Lymph Node Metastasis Classification (8th Edition), including inflammatory breast cancer For currently diagnosed breast cancer, prior systemic anticancer therapy (eg, neoadjuvant therapy or adjuvant therapy) includes, but is not limited to, chemotherapy, anti-HER2 therapy (eg, trastuzumab emtansine, pertuzumab, lapatinib, neratinib or other tyrosine kinase inhibitors), hormone therapy, or anti-cancer radiotherapy (RT), except for treatments planned under this study condition Previous treatment with anthracyclines or taxane for any malignant tumor History of ductal carcinoma in situ (DCIS) and/or lobular carcinoma in situ (LCIS), treatment of ipsilateral breast cancer with systemic therapy, hormone therapy, or RT, followed by invasive cancer, patients treated with DCIS/LCIS only surgery and/or RT for contralateral DCIS may be enrolled in the study. Prior to randomization, cardiopulmonary dysfunction according to any of the following: history of NCI CTCAE v4.0 ≥3 symptomatic congestive heart failure or New York College of Cardiology (NYHA) standard classification≥ II, angina requiring antianginal drugs, severe arrhythmias not treated with appropriate medical therapy, severe conduction abnormalities, or clinically significant valvular disease, high-risk, uncontrolled arrhythmias (i.e., atrial tachycardia with > resting rate). 100/min, significant ventricular arrhythmia [ventricular tachycardia], or high-grade atrioventricular (AV) block [second-degree AV block type 2, or third-degree atrioventricular block]), significant symptoms associated with left ventricular dysfunction, arrhythmia, or myocardial ischemia (grade ≥2), myocardial infarction within 12 hours prior to randomization; with uncontrolled hypertension (systolic blood pressure> 180 mmHg and/or diastolic blood pressure > 100 mmHg; ECG findings show transmural infarction; Oxygen therapy is required Prior malignancy within 5 years prior to randomization, with negligible risk of metastasis or death, except for malignancy that is expected to heal after treatment (i.e., appropriately treated carcinoma in situ or basal or squamous cell skin cancer). Known allergic or hypersensitivity to any component of the docetaxel, carboplatin, cyclophosphamide, or epirubicin preparations; Allergic or hypersensitivity reactions are known to filgrastim, pegfilgrastim, or granulocyte-macrophage colony-stimulating factor (GM-CSF) preparations Patients with serious infections (including but not limited to hospitalization due to infectious complications, bacteremia, or severe pneumonia) that occurred within 4 weeks prior to initiation of study treatment, who received therapeutic oral or intravenous antibiotics within 2 weeks prior to initiation of study treatment, and who received prophylactic antibiotic therapy (such as prophylaxis for urinary tract infection or prevention of chronic obstructive pulmonary disease) may be enrolled. Pregnant or lactating women, or women planning to become pregnant during the study period. Poorly controlled hypertension (defined as: systolic blood pressure > 150 mmHg and/or diastolic blood pressure >100 mmHg) Mental illness, cognitive impairment, inability to understand the trial protocol and side effects, and 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.
Facility Information:
Facility Name
Breast cancer institute of Fudan University Cancer Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhi-Ming Shao, MD
Phone
86-21-641755901105
Email
zhimingshao@yahoo.com
First Name & Middle Initial & Last Name & Degree
Lei Fan, MD
Phone
86-21-641755901105
Email
cmchen@medmail.com.cn
First Name & Middle Initial & Last Name & Degree
Zhi-Ming Shao, MD
First Name & Middle Initial & Last Name & Degree
Min He, MD
First Name & Middle Initial & Last Name & Degree
Linxiaoxi Ma, MD
First Name & Middle Initial & Last Name & Degree
Ying Zhou

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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TCb vs EC-T in High Risk ER+/HER2- Breast Cancer

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