A Single-center, Prospective Cohort Study of Neoadjuvant Anti-PD-1 Plus Chemotherapy in Locally Advanced Resectable Esophageal Squamous Cell Carcinoma
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Major pathological regression (MPR) rate
研究概览
简要总结
The purpose of this study is to evaluate the outcomes and identify predictors of neoadjuvant anti-PD-1 plus chemotherapy in locally advanced resectable esophageal squamous cell carcinoma (ESCC). In this single-center cohort study, we are aiming to (1) evaluate the therapeutic efficacy and survival benefits on patients with locally advanced resectable ESCC (cT3-4aN0-1M0); (2) evaluate the value of genomic indicators including MMR alternation status in predicting therapeutic responses and prognosis; (3) evaluate the value of transcriptomic indicators including B cell lineage features in predicting therapeutic responses and prognosis; (4) evaluate the value of microbial and metabolite indicators in predicting therapeutic responses and prognosis. Whole exome sequencing, RNA sequencing, 16S rRNA sequencing and Liquid Chromatography with tandem mass spectrometry (LC-MS-MS) of samples of patients to neoadjuvant chemoimmunotherapy before and after treatment are performed to explore the mechanisms of drug resistance and identification of predictive and prognosis biomarkers.
详细描述
Multiple clinical trials investigated the safety and feasibility of neoadjuvant anti-PD-1 plus chemotherapy in esophageal squamous cell carcinoma (ESCC). However, the efficacy of neoadjuvant chemoimmunotherapy was undetermined and existing biomarkers failed to provide stable prediction of therapeutic responses. This study seek to further evaluate the clinical outcomes and identify biological predictors of neoadjuvant anti-PD-1 plus chemotherapy in locally advanced resectable esophageal squamous cell carcinoma (ESCC). In this single-center cohort study, our aims include:
- evaluate the therapeutic efficacy and survival benefits on patients with locally advanced resectable ESCC (cT3-4aN0-1M0);
- evaluate the value of genomic indicators in predicting therapeutic responses and prognosis;
- evaluate the value of transcriptomic indicators in predicting therapeutic responses and prognosis;
- evaluate the value of microbial and metabolite indicators in predicting therapeutic responses and prognosis. Whole exome sequencing, RNA sequencing, 16S rRNA sequencing and Liquid Chromatography with tandem mass spectrometry (LC-MS-MS) of samples of responders and non-responders to neoadjuvant chemoimmunotherapy before and after treatment are performed to explore the mechanisms of drug resistance and identification of predictive and prognosis biomarkers, providing guidance to clinical decisions.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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 squamous cell carcinoma of the esophagus;
- •Tumors of the esophagus are located in the thoracic cavity;
- •Pre-treatment stage as cT3-4aN0-1M0 (AJCC/UICC 7th Edition) (In case of stage cT4a, curative resectability has to be explicitly verified by the local surgical investigator prior to randomization).
- •Age is between 18 years and 75 years,
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
- •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
- •Patients with non-squamous cell carcinoma histology;
- •Patients with advanced inoperable or metastatic esophageal cancer;
- •Pre-treatment stage as cT1-2N0-1M0 (AJCC/UICC 7th Edition);
- •Pre-treatment stage as cN2-3 or cT4b(non-curatively-resectable verified by the local surgical investigator, AJCC/UICC 7th Edition);
- •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.
- •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;
- •Allergy to any drugs;
- •Participation in another intervention clinical trial with interference to the therapeutic 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 Anti-PD-1 Plus Chemotherapy Group
Patients with locally advanced resectable ESCC (cT3-4aN0-1M0) who receive neoadjuvant anti-PD-1 plus chemotherapy and donate biological samples
干预措施: neoadjuvant anti-PD-1 plus chemotherapy (Drug)
结局指标
主要结局
Major pathological regression (MPR) rate
时间窗: Up to the date of pathological reports obtained since the date of enrollment, up to 6 months
The resected specimen following neo-adjuvant treatment are assessed by using standardised work up of the resection specimen in the pathology department and standardised histological criteria for tumour regression grading. MPR was defined as ≤10% residual viable tumor.
次要结局
- objective response rate (ORR)(36 months after the last subject participating in)
- The correlation between detection of genomic, immune, microbial and metabolite features and the rate of therapeutic responses.(36 months after the last subject participating in)
- overall survival (OS)(36 months after the last subject participating in)
- Pathological response rate(pCR)(Up to the date of pathological reports obtained since the date of enrollment, up to 6 months)
- Progression-free survival(PFS)(36 months after the last subject participating in)