A Single-Arm Phase II Trial of Neoadjuvant Toripalimab, Docetaxel, Plus Carboplatin in Patients With Localized Triple-Negative Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 51
- 试验地点
- 1
- 主要终点
- Pathological complete response (pCR) rate
研究概览
简要总结
This study aims to investigate efficacy and safety of neoadjuvant toripalimab plus docetaxel and carboplatin in patients with localized triple-negative breast cancer.
详细描述
Neoadjuvant chemotherapy combined with immunotherapy is the recommended therapeutic approach for patients with localized triple-negative breast cancer (TNBC). The combination regimen improved the pCR rate of triple negative breast cancer, but its side effects also increased. In the KEYNOTE-522 trial, 78% of patients receiving pembrolizumab combined with anthracycline and paclitaxel chemotherapy experienced grade 3 or higher adverse reactions, while the incidence of grade 3 or higher adverse events for patients receiving tislelizumab plus nab-paclitaxel and carboplatin in the CTRIO study was 53.2%. Toripalimab (an anti PD-1 monoclonal) combined with paclitaxel (albumin binding type) for first-line treatment of recurrent or metastatic TNBC was recently approved based on the results from the TORCHLIGHT study. This study aims to investigate efficacy and safety of neoadjuvant toripalimab plus docetaxel and carboplatin in patients with localized TNBC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 69 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Pathologically confirmed TNBC. ER and PR negatives are defined as < 10% of cells expressing hormone receptors by IHC analysis. HER2 negative is defined as IHC 0 or 1+, or ISH-negative.
- •Treatment-naive clinical stage T1-4N1-N3 or T2-4N0 localized TNBC.
- •Female patients aged ≥18 years, < 70 years.
- •Able to comply with the required protocol and follow-up procedures.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Life expectancy ≥12 weeks.
- •Adequate hematological function: Absolute neutrophil count (ANC) ≥1.5 x 109/L, and Platelet count ≥90 x 109/L, and Hemoglobin ≥90 g/L (may be transfused to maintain or exceed this level).
- •Adequate liver function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN), Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 1.5 x ULN.
- •Adequate renal function: Serum creatinine ≤ 1.5 x ULN, and creatinine clearance ≥ 50 ml/min.
- •Subjects should not be pregnant or breast-feeding.
排除标准
- •Inflammatory breast cancer or stage IV breast cancer.
- •Prior systemic antitumor treatment for any malignancy, including chemotherapy, radiotherapy, immunotherapy and targeted therapy.
- •History of another malignancy in the last 5 years with the exception of the following: other malignancies cured by surgery alone and having a continuous disease-free interval of 5 years are permitted. Cured basal cell carcinoma of the skin and cured in situ carcinoma of the uterine cervix are permitted.
- •Inability to comply with protocol or study procedures.
- •Subjects with active, known or suspected autoimmune disease. Subjects in conditions not expected to recur in the absence of an external trigger, or not requiring systemic treatment are permitted to enroll.
- •Previous history of interstitial lung disease/pneumonia.
- •Patient who has had an allogeneic tissue/solid organ transplant.
- •A serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study.
- •A serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease.
- •Any unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic disease).
- •Patient who has active serious infection (e.g. pyrexia of or 38.0℃ over)
- •Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
- •Women who are pregnant or nursing.
研究组 & 干预措施
Neoadjuvant TCb+Toripalimab
Patients receive toripalimab (240 mg) plus docetaxel and carboplatin (AUC=4) on day 1 of each 21-day cycle for 6 cycles.
干预措施: Docetaxel (Drug)
Neoadjuvant TCb+Toripalimab
Patients receive toripalimab (240 mg) plus docetaxel and carboplatin (AUC=4) on day 1 of each 21-day cycle for 6 cycles.
干预措施: Carboplatin (Drug)
Neoadjuvant TCb+Toripalimab
Patients receive toripalimab (240 mg) plus docetaxel and carboplatin (AUC=4) on day 1 of each 21-day cycle for 6 cycles.
干预措施: Toripalimab (Drug)
结局指标
主要结局
Pathological complete response (pCR) rate
时间窗: 1 week after surgery
The number of patients with pCR out of the total number of participants using a definition of ypT0/Tis ypN0 after neoadjuvant therapy and surgery.
次要结局
- Rate of Residual Cancer Burden (RCB) of 0-1(1 year)
- Objective Response Rate (ORR)(1 year)
- Event-Free Survival (EFS)(3 years after the last patient is enrolled)
- Safety of the combination therapy(1 year)
研究者
Si-Yu Wang
Professor
Sun Yat-sen University