Clinical trial NCT05871918: 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
Overall status: UNKNOWN
Phase: PHASE3
Conditions: HER-2 Positive Breast Cancer
Lead sponsor: Tianjin Medical University Cancer Institute and Hospital
Sponsor class: OTHER
First posted: 2023-05-23
Enrollment: 832
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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breast cancer,Subjects will be treated until disease progression, toxicity is intolerable, informed consent is withdrawn, and investigators determine that medication must be discontinued.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.

Eligibility criteria: Inclusion Criteria:

1. Age: 18 \~70 years old, female;
2. Histologically confirmed patients with previously untreated stage Ⅱ-Ⅲ HER2-positive breast cancer;
3. HER-2 positive breast cancer, defined as immunohistochemical (IHC) detection of 3+ or in situ hybridization (FISH) results of HER2 gene amplification;
4. There is at least one measurable objective lesion according to RECIST 1.1 criteria;
5. ECOG Physical fitness score is 0-2;
6. Left ventricular ejection fraction LVEF≥50%;
7. Bone marrow function: neutrophils ≥1.5×109/L, platelets ≥100×109/L, hemoglobin ≥90g/L;
8. 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;
9. 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
10. 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:

1. Stage IV (metastatic) breast cancer patients;
2. Patients with inflammatory breast cancer
3. 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)
4. 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;
5. Patients with severe systemic infection or accompanied by other serious diseases;
6. Have developed other malignant tumors within the previous 5 years, except for cured cervical carcinoma in situ and non-melanoma skin cancer;
7. 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;
8. Patients who participated in other studies within 30 days prior to the first dose of the investigational drug;
9. Patients deemed unsuitable for this study by the investigator.
10. The patient has good compliance with the planned treatment, can understand the research process of the study and sign the written informed consent.

Primary outcomes:
measure: 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
timeFrame: Up to approximately 24 weeks
Secondary outcomes:
measure: Event-Free Survival (EFS)
timeFrame: Up to approximately 3 years
measure: Invasive Disease-Free Survival (iDFS)
timeFrame: Up to approximately 3 years
measure: Overall survival (OS)
timeFrame: Up to approximately 3 years
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Breast Oncology, Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
Study officials:
References: