Neoadjuvant Chemotherapy Combined With Toripalimab for HR+/HER2- Breast Cancer : a Prospective, Single-arm, Multi-center Study (NEOTORCH-BREAST01)
Overview
- Phase
- Phase 2
- Intervention
- Neoadjuvant Chemotherapy in Combination with Toripalimab
- Conditions
- HR+/HER2- Breast Cancer
- Sponsor
- First Affiliated Hospital of Zhejiang University
- Enrollment
- 30
- Locations
- 11
- Primary Endpoint
- pathologic complete response（PCR）
- Status
- Recruiting
- Last Updated
- 8 months ago
Overview
Brief Summary
This study is a prospective, single arm, multi-center phase II clinical trial. The primary study objective is to evaluate the pathologic complete response（PCR）and RCB0-1 ratio of neodjuvant treatment of HR+/HER2- breast cancer with Toripalimab combined with neoadjuvant chemotherapy and sequential Toripalimab monoclonal antibody, including the incidences and types of adverse events. The secondary study objective is to observe and evaluate the disease-free survival (DFS), Progression-Free-Survival (PFS ),and Objective Response Rate(ORR)
Detailed Description
1. Breast cancer is the most common malignant tumor among women worldwide, with 2.3 million women suffering from it every year. In China, the incidence rate of breast cancer is increasing year by year, with about 400000 new cases every year, which seriously threatens the life and health of women in China. Study population: participants with HR+/HER2- breast cancer confirmed by postoperative pathology according to American Joint Committee on Cancer (AJCC) / Union for International Cancer Control (UICC) 8th Tumor Node Metastasis (TNM) staging classification. 2. Sample size: single arm design was used in this study and 30 participants were estimated to be enrolled. 3. Histologically confirmed invasive breast cancer with tumor diameter\>1cm (T1c-3; N0-3; M0). All patients were pathohistologically confirmed as HR+/HER2- breast cancer. According to the breast cancer diagnosis and treatment guidelines and specifications of the Chinese Society of Clinical Oncology, Luminal B is divided into Luminal B (HER2 negative) and Luminal B (HER2 positive). Luminal B (HER2 negative) is ER/PR positive, HER2 negative and Ki-67 proliferation index is high or PR low expression. Luminal type B (HER2 positive) is ER/PR positive, HER2 positive (protein overexpression or gene amplification), and Ki-67 in any state. Therefore, HR+/HER2- breast cancer is a Luminal type breast cancer patient excluding HER2+. 4. Chemotherapy Phase 1: Epirubicin (or Liposomal Doxorubicin)+Cyclophosphamide, intravenous infusion of 100 mg/m2. Epirubicin (or 35 mg/m2 liposomal doxorubicin)+600 mg/m2 cyclophosphamide, starting from the first day of the week, for a total of 12 weeks. Chemotherapy Phase 2: Paclitaxel, administered intravenously at a dose of 260 mg/m2 every 3 weeks for a total of 12 weeks. During neoadjuvant chemotherapy and postoperative adjuvant therapy, use of Toripalimab: intravenous infusion of 240 mg, once every 3 weeks, combined with preoperative and postoperative adjuvant therapy for a total of 1 year. 5. Adverse events (AEs) management: To minimize the risk of AEs, the investigators will monitor carefully to determine whether or not they are within the expected range. Investigators will also conduct a thorough examination and adopt an appropriate system to take any necessary measures to deal with AEs.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Female patients aged 18-75 years old;
- •ECOG score is 0-1 points;
- •breast cancer meets the following standards: Histologically confirmed invasive breast cancer with tumor diameter\>1cm (T1c-3; N0-3; M0). All patients were pathohistologically confirmed as HR+/HER2- breast cancer. According to the breast cancer diagnosis and treatment guidelines and specifications of the Chinese Anti Cancer Association (2021 version), Luminal B is divided into Luminal B (HER2 negative) and Luminal B (HER2 positive). Luminal B (HER2 negative) is ER/PR positive, HER2 negative and Ki-67 proliferation index is high or PR low expression. Luminal type B (HER2 positive) is ER/PR positive, HER2 positive (protein overexpression or gene amplification), and Ki-67 in any state. Therefore, HR+/HER2- breast cancer is a Luminal type breast cancer patient excluding HER2+.
- •Pathological examination of PD-L1 expression:
- •The Combined Positive Score (CPS) refers to the percentage of PD-L1 positive cells (including tumor cells, lymphocytes, macrophages) in all tumor cells. Our center detected the PD-L1 antibody site as 22C
- •The functional level of major organs must meet the following requirements (no blood transfusion within 2 weeks before screening, no use of...)
- •Using leukocyte and platelet boosting drugs:
- •Blood routine: Absolute neutrophil count (ANC) greater than 1.5 × 109/L; platelet count (PLT) greater than 75 × 109/L; Hemoglobin (Hb) is greater than 90g/L; Lymphocyte count ≥ 1.5 × 109/L
- •Blood biochemistry: Total bilirubin (TBIL) is less than 1.5 × ULN; Alanine aminotransferase ALT and aspartate levels are less than 1.5 × ULN; Alkaline phosphatase is less than 2.5 × ULN; Urea nitrogen/ Urea (BUN/UREA) and creatinine (Cr) are less than 1.5 × ULN.
- •Cardiac ultrasound: Left ventricular ejection fraction (LVEF) greater than 55%.
Exclusion Criteria
- •Stage IV breast cancer.
- •Inflammatory breast cancer.
- •Previously received anti-tumor treatment or radiation therapy for any malignant tumor, excluding those that have been cured Malignant tumors such as cervical carcinoma in situ, basal cell carcinoma, or squamous cell carcinoma.
- •Simultaneously undergoing anti-tumor treatment in other clinical trials, including but not limited to chemotherapy and endocrine therapy. Treatment, biological therapy, bone improvement drug therapy, or immune checkpoint inhibitor therapy, etc.
- •The patient had undergone major surgical procedures unrelated to breast cancer within 4 weeks before the first administration of the study drug, or the patient has not fully recovered from such surgical procedures.
- •Serious heart disease or discomfort, including but not limited to the following diseases:
- •Diagnosed history of heart failure or systolic dysfunction (LVEF less than 50%).
- •High risk uncontrolled arrhythmias, such as atrial tachycardia, resting heart rate greater than 100bpm, significant ventricular arrhythmias (such as ventricular tachycardia), or higher-level atrioventricular block (i.e. Mobitz II second or third degree atrioventricular block).
- •Angina requiring medication for treatment. 4) Heart valve disease with clinical significance. 5) ECG shows transmural myocardial infarction. 6) Poor control of hypertension (systolic blood pressure greater than 180mmHg and/or diastolic blood pressure greater than 180mmHg after drug treatment) 100mmHg).
- •Uncontrolled active infections that require treatment; History of immunodeficiency, including HIV testing positive Sexual, or suffering from other acquired or congenital immunodeficiency diseases, or having a history of organ transplantation.
Arms & Interventions
Neoadjuvant Chemotherapy in Combination with Toripalimab
Epirubicin (or Liposomal Doxorubicin)+Cyclophosphamide, intravenous infusion of 100 mg/m2. Epirubicin (or 35 mg/m2 liposomal doxorubicin)+600 mg/m2 cyclophosphamide+ 240 mg Toripalimab, starting from the first day of the week, for a total of 12 weeks. Paclitaxel, administered intravenously at a dose of 260 mg/m2 every 3 weeks + 240 mg Toripalimab for a total of the following 12 weeks.
Intervention: Neoadjuvant Chemotherapy in Combination with Toripalimab
Neoadjuvant Chemotherapy in Combination with Toripalimab
Epirubicin (or Liposomal Doxorubicin)+Cyclophosphamide, intravenous infusion of 100 mg/m2. Epirubicin (or 35 mg/m2 liposomal doxorubicin)+600 mg/m2 cyclophosphamide+ 240 mg Toripalimab, starting from the first day of the week, for a total of 12 weeks. Paclitaxel, administered intravenously at a dose of 260 mg/m2 every 3 weeks + 240 mg Toripalimab for a total of the following 12 weeks.
Intervention: HR+ HER2 breast cancer
Outcomes
Primary Outcomes
pathologic complete response（PCR）
Time Frame: 2 years
The primary study objective is to evaluate the pathologic complete response（PCR） of neoadjuvant treatment of HR+/HER2- breast cancer with Toripalimab combined with neoadjuvant chemotherapy and sequential Toripalimab monoclonal antibody,
RCB 0-1 Ratio
Time Frame: 2 years
Secondary Outcomes
- Disease-free survival (DFS)(3 years)
- Progression-Free-Survival (PFS)(3 years)
- Objective Response Rate(ORR)(3 years)