Selected Chemotherapy Combined Immunotherapy Treated High Risk Patient After Neoadjuvant Chemoradiotherapy in Resected Locally Advanced Esophageal Squamous Cell Carcinoma: an Exploratory Study
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Complete pathologic response rate
研究概览
简要总结
Tislelizumab combined with chemotherapy sequential neoadjuvant therapy for non-cCR patients after neoadjuvant chemoradiotherapy in locally advanced ESCC. And then the patients would receive surgery and adjuvant therapy according to the postoperative pathological results. It is expected that through this study, some high-risk patients could obtain better efficacy and prolong patient survival. At same time, low risk patients could avoid increasing perioperative complications and surgical risks, so that more patients could benefit from neoadjuvant treatment. The investigators aimed to explore a more accurate comprehensive treatment mode for patients with esophageal squamous cell carcinoma, and provide a certain scientific basis for the formulation of esophageal cancer diagnosis and treatment norms in China.
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
- •1.Histologically confirmed ESCC；
- •2.Clinical stage T2N0-1M0, T3N0M0, T3N1M0, T1-3N2M0（II-III) (AJCC 8 TNM classif tion);
- •3.Locally advanced ESCC that can be treated surgically evaluated before treatment;
- •4.At least one measurable lesion in accordance with RECIST 1.1;
- •5.Have a performance status of 0 or 1 on the ECOG Performance Scale;
- •6.Expected survival time is greater than 6 months;
- •7.The important organs functions meet the following requirements:the absolute neutrophil count(ANC) ≥1.5×109/L; the platelet count ≥100×109/L; hemoglobin ≥90g/L; bilirubin is less than or equal to 1.5 times ULN, ALT and AST less than or equal 2.5 times UILN; creatinine clearance rate(CCr) ≥50mL/min; the thyroid function is normal;
- •8.Female subjects of childbearing potential have a negative pregnancy test and must agree to take effective contraceptive measures during the study period and within 3 months after the last dose;
- •9.Be willing and able to provide written informed consent/assent for the trial.
排除标准
- •1.The patient have received radiotherapy, chemotherapy, hormone therapy, surgery, or molecular-targeted therapy;
- •2.Confirmed patients with distant metastasis by CT imaging;
- •3.The subject has previous or co-existing other malignancies (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix);
- •4.The subject had previously received other anti-pd-1 antibody therapy or other immunotherapy targeting pd-1 / pd-L1;
- •5.Patients with active autoimmune disease or documented autoimmune disease or symptoms requiring systemic hormone therapy or anti-autoimmune drug therapy;
- •6.Patients with immunodeficiency or who were still receiving systemic steroid hormone therapy (prednisone > 10 mg/ day or other equivalent drugs) or other forms of immunosuppressive therapy 7 days prior to the first dose of neoadjuvant therapy in this study;
- •7.Clinical ascites or pleural effusion requiring therapeutic puncture or drainage;
- •8.The subject with uncontrol cardiac clinical symptoms or diseases, such as :(1) nyha class 2 or more heart failure (2) unstable angina pectoris (3) myocardial infarction within 1 year (4) clinically significant ventricular or ventricular arrhythmias requiring treatment or intervention;
- •9.Abnormal coagulation function (PT>16s, APTT>43s, TT>21s, Fbg> 2G /L), bleeding tendency or receiving thrombolytic or anticoagulant treatment;
- •10.The subject is present (within 3 months) with esophageal varices, active gastric and duodenal ulcers, ulcerative colitis, portal hypertension and other gastrointestinal diseases, or with active bleeding from unresected tumors, or other conditions that may cause gastrointestinal bleeding or perforation as determined by the investigator;
- •11.Past or present severe bleeding (bleeding >30 ml within 3 months), hemoptysis (fresh blood >5 ml within 4 weeks) or thromboembolism events (including stroke events and/or TRANSIENT ischemic attack) within 12 months;
- •12.Patients with active infection who still required systemic treatment 7 days before the first dose of neoadjuvant therapy in this study;
- •13.Patients with past or present objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radioactive pneumonia, drug-related pneumonia, severely impaired lung function, etc;
- •14.Senior or uncontrolled virus injection: HIV, TP, hepatitis virus;
- •15.Senior or uncontrolled virus injection: HIV, TP, hepatitis virus;
- •16.Patients who had participated in clinical trials of other drugs within 4 weeks;
- •17.The live vaccine was administered less than 4 weeks prior to study administration or possibly during the study period;
- •18.Have a history of mental illness or psychiatric substance abuse;
- •19.The subject cannot or does not agree to bear the cost of the self-paid portion of the examination and treatment, except for the clinical study drug, combined chemoradiotherapy, and SAE associated with the clinical study drug;
- •20.Other patients whom the medical practitioner considers inappropriate for inclusion.
研究组 & 干预措施
Total neoadjuvant therapy
The patients would receive neoadjuvant chemoradiotherapy treatment firstly. And then evaluated efficacy according to RECIST 1.1. If patients with cCR would receive surgery treatment after 4-6 weeks. After surgery, patients with pCR would always perform surveillance and patients with non-pCR would receive immunotherapy alone treatment. If patients evaluated as PD, they would receive new treatment regimen after MDT discussed. Other patients with PR and SD would receive 2 cycles of neoadjuvant immunochemotherapy. And then, Efficacy of immunochemotherapy would be evaluated according to RECIST 1.1. For patients suitable for surgery, surgery should be performed after 4-6 weeks of immunotherapy. After surgery, the patients with R0 resection would divided into two groups, if patients with pCR would always perform surveillance and patients with non-pCR would receive immunotherapy treatment. Other patients without R0 resection would receive new treatment regimen after MDT discussed.
干预措施: Tirelizumab (Drug)
Total neoadjuvant therapy
The patients would receive neoadjuvant chemoradiotherapy treatment firstly. And then evaluated efficacy according to RECIST 1.1. If patients with cCR would receive surgery treatment after 4-6 weeks. After surgery, patients with pCR would always perform surveillance and patients with non-pCR would receive immunotherapy alone treatment. If patients evaluated as PD, they would receive new treatment regimen after MDT discussed. Other patients with PR and SD would receive 2 cycles of neoadjuvant immunochemotherapy. And then, Efficacy of immunochemotherapy would be evaluated according to RECIST 1.1. For patients suitable for surgery, surgery should be performed after 4-6 weeks of immunotherapy. After surgery, the patients with R0 resection would divided into two groups, if patients with pCR would always perform surveillance and patients with non-pCR would receive immunotherapy treatment. Other patients without R0 resection would receive new treatment regimen after MDT discussed.
干预措施: Paclitaxel (Drug)
Total neoadjuvant therapy
The patients would receive neoadjuvant chemoradiotherapy treatment firstly. And then evaluated efficacy according to RECIST 1.1. If patients with cCR would receive surgery treatment after 4-6 weeks. After surgery, patients with pCR would always perform surveillance and patients with non-pCR would receive immunotherapy alone treatment. If patients evaluated as PD, they would receive new treatment regimen after MDT discussed. Other patients with PR and SD would receive 2 cycles of neoadjuvant immunochemotherapy. And then, Efficacy of immunochemotherapy would be evaluated according to RECIST 1.1. For patients suitable for surgery, surgery should be performed after 4-6 weeks of immunotherapy. After surgery, the patients with R0 resection would divided into two groups, if patients with pCR would always perform surveillance and patients with non-pCR would receive immunotherapy treatment. Other patients without R0 resection would receive new treatment regimen after MDT discussed.
干预措施: Carboplatin (Drug)
Total neoadjuvant therapy
The patients would receive neoadjuvant chemoradiotherapy treatment firstly. And then evaluated efficacy according to RECIST 1.1. If patients with cCR would receive surgery treatment after 4-6 weeks. After surgery, patients with pCR would always perform surveillance and patients with non-pCR would receive immunotherapy alone treatment. If patients evaluated as PD, they would receive new treatment regimen after MDT discussed. Other patients with PR and SD would receive 2 cycles of neoadjuvant immunochemotherapy. And then, Efficacy of immunochemotherapy would be evaluated according to RECIST 1.1. For patients suitable for surgery, surgery should be performed after 4-6 weeks of immunotherapy. After surgery, the patients with R0 resection would divided into two groups, if patients with pCR would always perform surveillance and patients with non-pCR would receive immunotherapy treatment. Other patients without R0 resection would receive new treatment regimen after MDT discussed.
干预措施: Neoadiuvant radiotherapy (Radiation)
结局指标
主要结局
Complete pathologic response rate
时间窗: 3 months
Definition of complete pathologic response is "no cancer cell, including lympho nodes" which corresponds with tumor regression score 0. Definition of pathologic response is as follows. Tumor regression score Grade 0 and 1 will be defined as "responder" and 2 and 3 will be considered as "non-responders"
Incidence of adverse events
时间窗: 6 months
Number of participants with treatment-related adverse events as assessed by Number of participants with treatment-related adverse events as assessed by treatment-related adverse events assessed by CTCAE v4.0
次要结局
- Clinical Complete Remission(3 months)
- Major Pathological Remission rate(3 months)
- Objective Remission Rate(3 months)
- Rate of R0 resection(3 months)
- Events Free Survival(Through study completion, an average of 1 year.)
- Overall Survival(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months.)
研究者
Yongtao Han
Chief of Thoracic Surgery
Sichuan Cancer Hospital and Research Institute