Neoadjuvant Immunotherapy Combined With Chemoradiotherapy Versus Neoadjuvant Chemoradiotherapy for Locally Advanced Resectable Esophageal Squamous Cell Carcinoma (cII-III Stage): A Multi-center Prospective Randomized Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 176
- 试验地点
- 1
- 主要终点
- Pathological response rate(pCR)
研究概览
简要总结
The purpose of this study was to evaluate the safety, feasibility and outcome of anti-PD-1 antibody (Tislelizumab, BeiGene) combined with neoadjuvant chemoradiotherapy versus neoadjuvant chemoradiotherapy followed by minimally invasive esophagectomy for locally advanced resectable esophageal squamous cell carcinoma (cII-III Stage) patient.
详细描述
It is a prospective randomized phase II&III clinical trial sponsored by Shanghai Zhongshan Hospital with other twelve hospitals in China participating in. 476 patients with locally advanced resectable esophageal squamous cell carcinoma (cII-III Stage) are recruited and randomly assigned into the neoadjuvant chemoradiotherapy combined with immunotherapy group (nCRT plus anti-PD-1 Group) and the neoadjuvant chemoradiotherapy group (nCRT Group) according to the proportion of 1:1. The safety, efficacy of protocols and prognosis of patients are compared between the two regimens.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Histologically-confirmed esophageal squamous cell carcinoma and whose tissue samples were taken before treatment;
- •Tumors of the esophagus are located in the thoracic cavity;
- •Pre-treatment stage as clinical II-III (AJCC/UICC 8th Edition)
- •Age is between 18 years and 75 years;
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and expected survival time ≥12 months;
- •Adequate cardiac function. All patients should perform ECG, and those with a cardiac history or ECG abnormality should perform echocardiography with the left ventricular ejection fraction > 50 %;
- •Adequate respiratory function with FEV1≥1.2L, FEV1%≥50% and DLCO≥50% shown in pulmonary function tests ;
- •Adequate bone marrow function (White Blood Cells >4x10^9 /L; Neutrophil >2.0×10^9 /L; Hemoglobin > 90 g/L; platelets>100x10^9 /L);
- •Adequate liver function (Total bilirubin <1.5x Upper Level of Normal (ULN); Aspartate transaminase(AST) and Alanine transaminase (ALT) <1.5x ULN);
- •Adequate renal function (Glomerular filtration rate (CCr) >60 ml/min; serum creatinine (SCr) ≤120 µmol/L);
- •The patient has provided written informed consent and is able to understand and comply with the study;
排除标准
- •Exclusion Criteria associated with Cancer:
- •Patients with histological non-squamous cell carcinoma;
- •Patients with advanced non-operable or metastatic esophageal cancer;
- •Pre-treatment stage as cM+, cN3 or cT4b(non-curatively-resectable verified by the local surgical investigator, AJCC/UICC 8th Edition) or cTis-1a, cT1bN0;
- •Patients with another previous or current malignant disease which is likely to interfere with treatment or the assessment of response in the judgement of the local surgical investigator;
- •Patients who have received or are receiving other chemotherapy, radiotherapy or targeted therapy;
- •Other Exclusion Criteria:
- •Patients with autoimmune diseases history;
- •Recently or currently taking Glucocorticoids or Immunosuppressants;
- •Patients who underwent immunotherapy in the past;
- •Allergy to any antibody drugs or allergy to Paclitaxel and Carboplatin.
- •Past or currently suffering from chronic or recurrent autoimmune diseases;
- •Patients with active infection of immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); HIV seropositivity; HBV DNA or HCV RNA positive;
- •Patients with organ transplantation (including autologous bone marrow transplantation and peripheral stem cell transplantation);
- •Patients with severe systematic intercurrent disease, such as active infection or poorly controlled diabetes; coagulation disorders; hemorrhagic tendency or under treatment of thrombolysis or anticoagulant therapy;
- •Any patient with a significant medical condition which is thought unlikely to tolerate the therapies. Such as cardiac disease (e.g. symptomatic coronary artery disease or myocardial infarction within last 12 months), clinically-significant lung disease, clinically-significant bone marrow, liver, renal function disorder;
- •Pregnant or lactating women and fertile women who will not be using contraception during the trial;
- •Participation in another intervention clinical trial with interference to the chemotherapeutic or chemoradiotherapeutic intervention during this study or during the last 30 days prior to informed consent;
- •Expected lack of compliance with the protocol.
研究组 & 干预措施
Neoadjuvant chemoradiotherapy combined with anti-PD-1 antibody
Neoadjuvant chemoradiotherapy (NCRT) combined with tislelizumab is performed followed by Ivor-Lewis or Mckeown esophagectomy in enrolled patients.
干预措施: Neoadjuvant Chemoradiotherapy (Procedure)
Neoadjuvant chemoradiotherapy combined with anti-PD-1 antibody
Neoadjuvant chemoradiotherapy (NCRT) combined with tislelizumab is performed followed by Ivor-Lewis or Mckeown esophagectomy in enrolled patients.
干预措施: Tislelizumab (Drug)
Neoadjuvant chemoradiotherapy combined with anti-PD-1 antibody
Neoadjuvant chemoradiotherapy (NCRT) combined with tislelizumab is performed followed by Ivor-Lewis or Mckeown esophagectomy in enrolled patients.
干预措施: Ivor-Lewis or Mckeown Esophagectomy(Mckeown Esophagectomy recommended) (Procedure)
Neoadjuvant chemoradiotherapy
Neoadjuvant chemoradiotherapy (NCRT) is performed followed by Ivor-Lewis or Mckeown esophagectomy in enrolled patients.
干预措施: Neoadjuvant Chemoradiotherapy (Procedure)
Neoadjuvant chemoradiotherapy
Neoadjuvant chemoradiotherapy (NCRT) is performed followed by Ivor-Lewis or Mckeown esophagectomy in enrolled patients.
干预措施: Ivor-Lewis or Mckeown Esophagectomy(Mckeown Esophagectomy recommended) (Procedure)
结局指标
主要结局
Pathological response rate(pCR)
时间窗: Up to the date of pathological reports obtained since the date of randomization, up to 12 months
The resected specimen following neo-adjuvant treatment are assessed by using standardized work up of the resection specimen in the pathology department and standardized histological criteria for tumor regression grading. The degree of histomorphologic regression is clarified into four categories as follows: grade 1, no evidence of vital residual tumor cells (pathological complete response); grade 2, less than 10% vital residual tumor cells; grade 3, 10 to 50%; and grade 4, more than 50%.
Overall survival(OS)
时间窗: Up to the date of death of any causes since the date of randomization, up to 36 months
次要结局
- Number and Location of positive lymph nodes(Up to the date of pathological reports obtained since the date of randomization, up to 12 months)
- Treatment related complications(Up to 1 month after surgery since the data of randomization, up to 13 months)
- Progression-free survival(PFS)(Up to the date of disease recurrence since the date of randomization, up to 36 months)
- R0 resection rate(Up to the date of pathological reports obtained since the date of randomization, up to 12 months)
- Overall Quality of life(Up to the end of follow-up since the data of surgery, up to 36 months)
- Quality of life in eating and swallowing function(Up to the end of follow-up since the data of surgery, up to 36 months)
- Recurrence-free survival (RFS)(Up to the date of disease recurrence since the date of surgery, up to 36 months)
- Correlation between genetic profile and tumor response(Up to the end of follow-up since the data of surgery, up to 36 months)