A Prospective, One-arm, Single-center, Phase Ⅱ Clinical Study of Carrelizumab Combined With Chemotherapy and Antiangiogenic Drugs in the Neoadjuvant Treatment of Resectable Esophageal Squamous Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Pathological Complete Response (PCR)
研究概览
简要总结
China with high incidence of esophageal cancer, the number of new cases and deaths account for about 50% of the world every year. In the past few decades, surgery, radiotherapy, chemotherapy and other treatments were continuously improved, however, the mortality of esophageal squamous cell carcinoma patients was not significantly decreased.
For patients with locally advanced esophageal cancer, direct surgery is not effective. It is difficult to achieve radical resection by surgery merely, and even if many patients receive surgery, they may eventually have tumor recurrence and poor survival rate. Therefore, it is necessary to explore effective perioperative neoadjuvant treatment to reduce the risk of postoperative recurrence and improve the postoperative survival rate of patients.
According to the reports, the expression of PD-L1 in esophageal cancer was about 41.4%. Therefore, PD-1/ PD-L1 immunocheckpoint inhibitor may become a new method for the treatment of esophageal cancer. Preliminary clinical results showed that immunotherapy combined with chemoradiotherapy provided a synergies antitumor effect. Multiple clinical results showed that Carrillizumab provided higher overall response rate for advanced esophageal cancer.
However, in patients with locally advanced esophageal cancer, the efficacy of Carrillizumab combined with chemotherapy and apatinib for sequential radical surgery is still unclear. The purpose of this study is to observe and evaluate the efficacy and safety of Carrillizumab combined with chemotherapy and antiangiogenic drugs in the neoadjuvant therapy of resectable esophageal squamous cell carcinoma.
详细描述
Esophageal cancer is a common malignant tumor of the digestive tract. Every year, there are about 400,000 new cases of esophageal cancer in the world and about 300,000 people dying of this disease. China with high incidence of esophageal cancer, the number of new cases and deaths account for about 50% of the world every year. In the past few decades, surgery, radiotherapy, chemotherapy and other treatments were continuously improved, however, the mortality of esophageal squamous cell carcinoma patients was not significantly decreased. Early local invasion, lymph node metastasis and distant metastasis are the main causes of poor prognosis for the patients with esophageal squamous cell carcinoma.
For patients with locally advanced esophageal cancer, direct surgery is not effective. It is difficult to achieve radical resection by surgery merely, and even if many patients receive surgery, they may eventually have tumor recurrence and poor survival rate. Therefore, it is necessary to explore effective perioperative neoadjuvant treatment to reduce the risk of postoperative recurrence and improve the postoperative survival rate of patients.
In recent years, PD-1 antibody is undoubtedly the most dazzling star in the field of tumor therapy. It shows excellent efficacy in of the different kind of tumors. According to the reports, the expression of PD-L1 in esophageal cancer was about 41.4% (Meta-analysis of 1350 Chinese and Japanese subjects showed that the over-expression of PD-L1 tended to decrease overall survival). Therefore, PD-1/ PD-L1 immunocheckpoint inhibitor may become a new method for the treatment of esophageal cancer. Preliminary clinical results showed that immunotherapy combined with chemoradiotherapy provided a synergies antitumor effect. Multiple clinical results showed that Carrillizumab provided higher overall response rate for advanced esophageal cancer. It also provided superior progression free survival and overall survival compared with Pembrolizuma and paclitaxel. 2020 Chinese Society Of Clinical Oncology esophagus cancer guidelines recommended Carrillizumab as the first level for squamous cell carcinomas.
However, in patients with locally advanced esophageal cancer, the efficacy of Carrillizumab combined with chemotherapy and apatinib for sequential radical surgery is still unclear. The purpose of this study is to observe and evaluate the efficacy and safety of Carrillizumab combined with chemotherapy and antiangiogenic drugs in the neoadjuvant therapy of resectable esophageal squamous cell carcinoma.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •signed informed consent;
- •patients age 18 to 75 years old
- •primary resectable, histologically confirmed esophageal squamous cell cancer;
- •Esophageal squamous cell carcinoma the clinical stage was IIA-IVA (according to AJCC TNM stage, 8th edition).
- •No distant metastasis, the diseases could be resectable assessed by thoracic oncologist;
排除标准
- •with significant cardiovascular disease;
- •current treatment with anti-viral therapy or HBV;
- •Female patients who are pregnant or lactating;
- •history of malignancy within 5 years prior to screening;
- •active or history of autoimmune disease or immune deficiency;
- •signs of distant metastases.
研究组 & 干预措施
Carillizumab
Preoperative neoadjuvant therapy for 2-3 cycles. Radical surgery is performed 4-6 weeks after the last dose. Postoperative radiotherapy is determined according to the clinical situation and pathological stage of the patient.
Carillizumab can be maintained for a maximum of 1 year. During the study, patients were be followed until disease progression, withdrawal of informed consent, loss of follow-up, or death.
干预措施: Carillizumab (Drug)
Carillizumab
Preoperative neoadjuvant therapy for 2-3 cycles. Radical surgery is performed 4-6 weeks after the last dose. Postoperative radiotherapy is determined according to the clinical situation and pathological stage of the patient.
Carillizumab can be maintained for a maximum of 1 year. During the study, patients were be followed until disease progression, withdrawal of informed consent, loss of follow-up, or death.
干预措施: Esophagectomy (Procedure)
Carillizumab
Preoperative neoadjuvant therapy for 2-3 cycles. Radical surgery is performed 4-6 weeks after the last dose. Postoperative radiotherapy is determined according to the clinical situation and pathological stage of the patient.
Carillizumab can be maintained for a maximum of 1 year. During the study, patients were be followed until disease progression, withdrawal of informed consent, loss of follow-up, or death.
干预措施: Samples (Other)
结局指标
主要结局
Pathological Complete Response (PCR)
时间窗: 1 month after surgery
No residual invasive tumor cells were found in the pathological examination of resected specimens.
次要结局
- 2-year and 5-year disease-free survival(2-year and 5-year after surgery)
- Major Pathological Response (MPR)(1 month after surgery)
- Objective Response Rate (ORR)(1 month after surgery)
- 2-year and 5-year overall survival(2-year and 5-year after surgery)
- Incidence of Treatment-related Adverse Events(1 month after surgery)
- R0 resection rate(1 month after surgery)
- The changes in the peripheral blood immunoprofile among non-PCR (NPCR) and PCR patients(3 month after surgery)