Randomized Controlled Clinical Study of Efficacy and Safety of Initumab Combined with Pyrrotinib and Chemotherapeutic Agents in Neoadjuvant Therapy for HER2-positive Breast Cancer with Different Treatment Cycles

Обзор

The purpose of this study was to explore the efficacy and safety of initumab combined with pyrrotinib and chemotherapy for 4 cycles and 6 cycles of neoadjuvant therapy for HER2-positive breast cancer, and to explore the efficacy and safety of continued use of initumab combined with pyrrotinib in pCR patients. This study adopted A prospective, randomized controlled, open-label design, and selected eligible subjects to be randomly divided into cohort A and Cohort B. Cohort A will receive initumab at initial load dose of 8mg/kg and maintenance dose of 6mg/kg intravenously on the first day of every three weeks for a total of 4 doses. Pyrrotinib 400mg orally once daily; Combined chemotherapy drugs (not limited, according to the actual clinical selection), a total of 4 cycles of administration. After surgery for breast cancer, initumab + pyrrotinib was selected as adjuvant therapy for pCR patients after surgery for 1 year (neoadjuvant therapy + adjuvant therapy for a total of 1 year, a total of 13 cycles of adjuvant therapy), and non-pCR patients were selected by doctors. Cohort B will receive initumab at initial load dose of 8mg/kg and maintenance dose of 6mg/kg intravenously on the first day of every three weeks. Pyrrotinib 400mg orally once daily; Combined chemotherapy drugs (not limited, according to the actual clinical selection), a total of 6 cycles of administration. After surgery for breast cancer, initumab + pyrrotinib was selected as adjuvant therapy for pCR patients after surgery for 1 year (neoadjuvant therapy + adjuvant therapy for a total of 1 year, and adjuvant therapy for a total of 11 cycles), and non-pCR patients were selected by doctors.

Вмешательства

• Препарат Cohort A will receive an initial load dose of 8mg/kg and a maintenance dose of 6mg/kg intravenously on the first day of every three weeks for a total of 4 doses
  Cohort A will receive initumab at initial load dose of 8mg/kg and maintenance dose of 6mg/kg intravenously on the first day of every three weeks for a total of 4 doses. Pyrrotinib 400mg orally once daily; Combined chemotherapy drugs (not limited, according to the actual clinical selection), a total of 4 cycles of administration
• Препарат Cohort B will receive an initial load dose of 8mg/kg and a maintenance dose of 6mg/kg intravenously on the first day of every three weeks for a total of 6 doses
  The initial loading dose of initumab was 8mg/kg, and the maintenance dose was 6mg/kg, which was administered intravenously on the first day of every three weeks. Pyrrotinib 400mg orally once daily; Combined chemotherapy drugs (not limited, according to the actual clinical selection), a total of 6 cycles of administration

Первичные конечные точки

• total Pathological Complete Response，tpCR [Срок оценки: After completion of neoadjuvant therapy, subjects' completely removed breast specimens and all sampled regional lymph nodes were evaluated]

Вторичные конечные точки (4)

• Overall Response Rate，ORR [Срок оценки: It refers to the percentage of cases that achieved complete response (CR) and partial response (PR) after neoadjuvant therapy as a percentage of the total number of evaluable cases]
• Event-Free Survival，EFS [Срок оценки: Refers to the time from enrollment to the first recorded recurrence of disease, disease progression, or death from any cause after surgery]
• Invasive Disease-Free Survival，iDFS [Срок оценки: Refers to the time from enrollment to the first occurrence of an aggressive ipsilateral tumor recurrence, aggressive countermeasure breast cancer, local/regional aggressive recurrence, distant recurrence, or death from any cause]
• Overall Survival [Срок оценки: Refers to the time from enrollment to death]

Критерии участия

inclusion criteria：

1\. Age ≥18 years old, while ≤70 years old, gender is not limited; 2.2. Invasive breast cancer confirmed histologically by air-core needle biopsy; According to AJCC breast cancer Staging System 8th edition, clinical staging was T1c-4, N0-3, M0.

3\. HER2 positive: IHC 3+ or IHC 2+ and FISH+ 4.Left ventricular ejection fraction (LVEF) ≥ 50% 5.ECOG physical condition score is 0 or 1 6.In the absence of blood transfusion or symptomatic treatment (granulocyte colony-stimulating factor/erythropoietin (EPO)/interleukin-11, etc.) within 14 days prior to initial administration, organ function must meet the following requirements Blood routine: absolute value of neutrophil (ANC) ≥1.5×109/L; Platelet (PLT) ≥100×109/L; Hemoglobin (Hb) ≥90g/L Blood biochemistry: Total bilirubin (TBIL) ≤1.5×ULN; ALT and AST≤1.5×ULN; BUN and Cr≤1.5×ULN; Creatinine clearance ≥50mL/min (Cockcroft-Gault formula) 7.Voluntarily participate in this study, sign informed consent, have good compliance and are willing to cooperate with follow-up

Критерии исключения

• Previous history of invasive breast cancer
• Bilateral breast cancer, inflammatory breast cancer (e.g., erythema and/or skin involvement, and/or pathological findings of tumor cells in the dermal lymphatic vessels), or clinical stage T1c, N0, M0
• Prior biopsy of primary tumor and/or axillary lymph node excision and/or excision
• Previous systemic treatment for breast cancer;
• A history of life-threatening hypersensitivity, or a known history of allergy to any component of the investigational drug;
• Participated in clinical trials of other drugs or medical devices within 4 weeks before the first drug use, and received treatment with experimental drugs or devices
• Patients who had undergone major surgery within 28 days prior to the first dose or planned to undergo major surgery during the study period
• Other malignant tumors (excluding cervical carcinoma in situ, non-melanoma skin cancer, localized prostate cancer, ductal carcinoma in situ) within the previous 5 years
• Active hepatitis, active tuberculosis or other serious infectious diseases, including but not limited to: Active hepatitis C virus (HCV) infection (HCV antibody positive but not RNA negative), or hepatitis B virus (HBV) infection (HBV surface antigen positive and HBV-DNA copy number >2000 IU/mL) or other serious infections requiring systemic treatment such as bacteremia, severe infectious pneumonia
• A history of immunodeficiency or other autoimmune diseases, including but not limited to human immunodeficiency virus (HIV) infection (HIV-positive), systemic lupus erythematosus, rheumatoid arthritis, or a history of organ transplantation
• Patients with a history of cardiovascular and cerebrovascular diseases, including: (1) unstable angina pectoris; (2) medically treatable or clinically significant arrhythmias; (3) myocardial infarction occurring within 6 months; (4) Heart failure, degree II and above atrioventricular block; (5) Cerebral infarction (except lacunar cerebral infarction), cerebral hemorrhage and other diseases occurring within 6 months
• Patients with poorly controlled hypertension (systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg under regular medication), or with a prior history of hypertensive crisis or hypertensive encephalopathy
• Pregnant and lactating female patients; Pregnant women of childbearing age who were positive in screening pregnancy test; Patients who are unwilling to use effective contraception throughout the trial period and for 6 months after the end of medication
• Other circumstances deemed inappropriate by the investigator to participate in the study

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT06868017 · OBU-BC-II-206

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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