中国临床试验注册中心 - 世界卫生组织国际临床试验注册平台一级注册机构

注册号： Registration number：	ChiCTR2400083321
最近更新日期： Date of Last Refreshed on：	2024-04-22 09:23:14
注册时间： Date of Registration：	2024-04-22 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	pT1b-cN0M0期食管癌ESD术后追加放化疗与追加外科手术疗效的实用性、前瞻性、非劣效性、非随机对照研究
Public title：	Efficacy of Chemoradiotherapy Versus Adjuvant Esophagectomy for Patients with Clinical Stage N0M0 and Pathological Stage T1b Esophageal Squamous Cell Carcinoma After Endoscopic Submucosal Dissection: A pragmatic, prospective, noninferiority, non-randomized controlled trial
注册题目简写：	EndoSurgery01
English Acronym：	EndoSurgery01
研究课题的正式科学名称：	pT1b-cN0M0期食管癌ESD术后追加放化疗与追加外科手术疗效的实用性、前瞻性、非劣效性、非随机对照研究
Scientific title：	Efficacy of Chemoradiotherapy Versus Adjuvant Esophagectomy for Patients with Clinical Stage N0M0 and Pathological Stage T1b Esophageal Squamous Cell Carcinoma After Endoscopic Submucosal Dissection: A pragmatic, prospective, noninferiority, non-randomized controlled trial
研究课题代号(代码)： Study subject ID：	KY2024010
在二级注册机构或其它机构的注册号： The registration number of the Partner Registry or other register：	ZSLCYJ202318

申请注册联系人：	徐佳昕	研究负责人：	周平红
Applicant：	Jiaxin Xu	Study leader：	Pinghong Zhou
申请注册联系人电话： Applicant telephone：	+86 137 6191 9446	研究负责人电话： Study leader's telephone：	+86 136 8197 1063
申请注册联系人传真： Applicant Fax：		研究负责人传真： Study leader's fax：
申请注册联系人电子邮件： Applicant E-mail：	xu.jiaxin1@zs-hospital.sh.cn	研究负责人电子邮件： Study leader's E-mail：	zhou.pinghong@zs-hospital.sh.cn
申请单位网址(自愿提供)： Applicant website(voluntary supply)：		研究负责人网址(自愿提供)： Study leader's website(voluntary supply)：
申请注册联系人通讯地址：	上海市徐汇区枫林路180号	研究负责人通讯地址：	上海市徐汇区枫林路180号
Applicant address：	180 Fenglin Road, Xuhui District, Shanghai	Study leader's address：	180 Fenglin Road, Xuhui District, Shanghai
申请注册联系人邮政编码： Applicant postcode：		研究负责人邮政编码： Study leader's postcode：
申请人所在单位：	复旦大学附属中山医院
Applicant's institution：	Zhongshan Hospital, Fudan University
研究负责人所在单位：	复旦大学附属中山医院
Affiliation of the Leader：	Zhongshan Hospital, Fudan University

是否获伦理委员会批准：	是
Approved by ethic committee：	Yes
伦理委员会批件文号： Approved No. of ethic committee：	B2024-111R	伦理委员会批件附件： Approved file of Ethical Committee：	查看附件View
批准本研究的伦理委员会名称：	复旦大学附属中山医院医学伦理委员会
Name of the ethic committee：	Medical Ethics Committee, Zhongshan Hospital, Fudan University
伦理委员会批准日期： Date of approved by ethic committee：	2024-04-03 00:00:00
伦理委员会联系人：	高鑫
Contact Name of the ethic committee：	Xin Gao
伦理委员会联系地址：	上海市徐汇区枫林路180号
Contact Address of the ethic committee：	180 Fenglin Road, Xuhui District, Shanghai
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 21 3158 7871	伦理委员会联系人邮箱： Contact email of the ethic committee：

研究实施负责（组长）单位：

复旦大学附属中山医院

Primary sponsor：

Zhongshan Hospital, Fudan University

研究实施负责（组长）单位地址：

复旦大学附属中山医院

Primary sponsor's address：

Zhongshan Hospital, Fudan University

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	上海市	市(区县)：
Country：	China	Province：	Shanghai	City：
单位(医院)：	复旦大学附属中山医院	具体地址：	上海市徐汇区枫林路180号
Institution hospital：	Zhongshan Hospital, Fudan University	Address：	180 Fenglin Road, Xuhui District, Shanghai

经费或物资来源：

复旦大学附属中山医院临床研究资助项目，重点项目，批准号ZSLCYJ202318

Source(s) of funding：

Clinical Research supported by Zhongshan Hospital, Fudan University, Key project, Approval No. ZSLCYJ202318

研究疾病：

食管鳞状细胞癌

Target disease：

Esophageal Squamous Cell Carcinoma

研究疾病代码：

2B70.1

Target disease code：

2B70.1

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

II期临床试验

Study phase：

2

研究设计：

非随机对照试验

Study design：

Non randomized control

研究目的：

通过实用性、前瞻性、非劣效性、非随机对照研究，对pT1b-cN0M0期食管癌ESD术后追加放化疗与追加外科手术的疗效进行比较。

Objectives of Study：

We aim to compare the efficacy of adding radiochemotherapy versus adding surgical intervention after ESD for pT1b-cN0M0 esophageal cancer through a practical, prospective, non-inferiority, non-randomized controlled study.

药物成份或治疗方案详述：

1.整体的研究设计和计划本研究为实用性、前瞻性、非劣效性、非随机对照研究 2.研究对象 2.1入选标准 1) 18-80周岁； 2) 影像学无淋巴结转移和远处转移者； 3) ESD术后病理证实为T1b期食管鳞状细胞癌（浸润至黏膜下层），且垂直切缘为阴性者； 4) 术前未进行新辅助治疗及靶向治疗等； 5) 签署知情同意书。 2.2排除标准 1) 同时或异时（5年内）恶性肿瘤个人史者； 2) 因严重心肺疾病、严重肾功能不全，无法耐受手术或放化疗患者； 3) 孕妇及哺乳期妇女； 4) 6个月内有心肌梗塞病史者； 5) 6个月内有脑梗死或脑出血病史者 2.3中途退出标准患者可以在研究的任何阶段不需要任何理由退出研究治疗和评定。如果发生以下情况患者必须退出： ① 撤回知情同意书； ② 在研究过程中参加了其他前瞻性临床研究。如果患者不能参加设定好的研究评估，研究者必须明确其原因并尽可能完整和准确的记录下来。退出程序：对于退出研究的患者，研究者必须询问其退出原因和是否发生任何不良事件。如果可能，研究者应对退出研究的患者进行结束访视和评定。退出研究的原因和日期（最后一次检测的日期）必须要记录在病例报告表上（CRF）。 3.病例数及分组方法根据文献报道，T1b食管鳞状细胞癌外科手术后3年的总体生存率为80%，T1b食管鳞状细胞癌ESD术后追加同步放化疗3年总体生存率为90%，本研究中假设试验组3年总体生存率为85%，对照组为80%，选取检验水准0.025（单侧检验），检验效能0.8，非劣效性界值为10%计算，每组所需样本量约101例，按10%脱落率计算，10%倾向性评分匹配失败率计算，每组所需样本量为120例，总样本量为240例。根据患者首选治疗类型进行分配入组。为了调整潜在的混杂因素，采用倾向性评分计算权重，相关因素包括年龄、性别、BMI、术前ASA评分、肿瘤位置、肿瘤长度、肿瘤宽度，单发或多发、浸润深度、脉管情况。 4.研究步骤 4.1筛选期患者需完善影像学检查排除证实无淋巴结转移或远处转移，提供ESD术后病理（常规所需）。结合纳入排除标准，各中心符合标准的患者将由一位专职负责患者入组的内镜医生与其进行谈话并签署知情同意书。收集患者年龄、性别、BMI、术前ASA评分、肿瘤位置、肿瘤长度、肿瘤宽度，单发或多发、浸润深度、脉管情况。按照患者意愿进入试验组或对照组，并完善生活质量评价（研究所需）。 4.2入选治疗期所有手术操作或治疗由1名医师，在另1名从事临床科研活动的医务人员的直接监督下完成。入选治疗期收集患者对照组：患者完善包括心肺功能、血检等术前常规检查，在ESD术后一个月后接受食管切除术，患者将接受开放、微创或两者结合的食管切除术（McKeown术式或Ivor Lewis术式），并至少进行完全两野淋巴结清扫。手术方式的选择将根据患者情况，肿瘤大小、位置等特点，由术者进行选择。根据NCCN和2022 CSCO食管癌诊疗指南[5]，应清扫至少15个淋巴结，包括胸上段食管旁、右喉返神经旁、胸中段食管旁、胸下段食管旁、左喉返神经旁、气管旁、隆突下、下肺韧带、膈肌旁等站的淋巴结。并对手术标本进行常规病理检查。试验组：患者将在ESD术后一个月后接受同步放化疗，方案：在第1、8、15、22和29天（每周为一周期；5周期）静脉注射卡铂（2毫克/毫升/分钟曲线下面积）和紫杉醇（50毫克/平方米体表面积）；且从第1天开始行外放疗，每天1次，每周5天，共23次，总剂量41.4Gy，每次1.8Gy。收集患者治疗期间病史资料以了解治疗情况和不良事件发生。 4.3随访期根据诊疗常规进行为期3年的随访，具体方案见下表（生活质量问卷为额外增加）： 3月 6月 12月 18月 24月 30月 36月内镜 √ √ √ √ √ √ √ 颈胸部增强CT √ √ √ 生活质量问卷 √ √ √ √ √ PET-CT √ √ √ 血液检测 √ √ √ √ √ √ 收集患者生存情况，不良事件发生率，内镜、CT、PET-CT检查结果和生活质量问卷分数。 5.研究终点主要研究终点 3年总体生存率（overall survival rate, OSR），定义为入组患者经过3年随访后，尚存活的病人数所占的比例。次要研究终点 3年无进展生存率（progress-free survival, PFS），定义为入组患者经过3年随访后，无进展和尚存活的病人数所占的比例，评估时间最长为36个月。肿瘤进展定义为影像学或临床的恶化。内镜检查发现非原位的T1a ESCC可通过内窥镜切除术进行治愈性切除，不被列为进展。总生存期（overall survival，OS），定义为从入组开始到最后一次随访或任何原因导致死亡的时间。无进展生存期（progression free survival, PFS），定义为从入组开始到最后一次随访、肿瘤进展或任何原因导致死亡的时间。生活质量评价，使用欧洲癌症研究和治疗组织的生活质量问卷C-30（EORTC QLQ-C30）和EORTC QLQ-OES18进行评估，患者将在招募当天和治疗后的第3、6、12和24个月完成问卷。 6.临床观察、随访和保证受试者依从性的措施临床观察：在院通过临床医生观察记录相关治疗情况和不良事件的发生。随访：安排专人通过电话及门诊就诊的方式进行随访。保证受试者依从性：入组患者必须进一步治疗及规律的随访以获得更长期的生存。

Description for medicine or protocol of treatment in detail：

1. Overall Study Design and planThis study was a pragmatic, prospective, non-inferiority, non-randomized controlled trial. 2.1 Inclusion criteria: 1) 18-80 years old; 2) without lymph node metastasis or distant metastasis on imaging; 3) Stage T1b esophageal squamous cell carcinoma (infiltrating into the submucosa) with negative vertical margin confirmed by pathology after ESD; 4) without preoperative neoadjuvant therapy or targeted therapy; 5) signed informed consent. 2.2 Exclusion criteria: 1) personal history of synchronous or metachronous (within 5 years) malignant tumors; 2) patients who could not tolerate surgery or radiotherapy or chemotherapy due to severe heart and lung diseases or severe renal insufficiency; 3) pregnant and lactating women; 4) patients with a history of myocardial infarction within 6 months; 2.3 Withdrawal Criteria Patients could withdraw from the study treatment and assessment at any stage of the study without any reason. Patients must withdraw if they: ① Withdraw informed consent; ② Participated in other prospective clinical studies during the study. If a patient is unable to participate in the scheduled study assessment, the investigator must identify the reasons for this and document them as completely and accurately as possible. Withdrawal Procedure: Patients who withdrew from the study had to be asked by the investigator about the reason for withdrawal and whether any adverse events had occurred. If possible, patients who withdrew from the study should be assessed by investigators at close-out visits. The reason for withdrawal from the study and the date of withdrawal (date of last test) must be recorded on the case report form (CRF). According to literature reports, the 3-year overall survival rate of T1b esophageal squamous cell carcinoma after surgery was 80%, and the 3-year overall survival rate of T1b esophageal squamous cell carcinoma after ESD plus concurrent chemoradiotherapy was 90%. In this study, the 3-year overall survival rate of the experimental group was 85%, and that of the control group was 80%. The test level was 0.025 (one-sided test), the test power was 0.8, and the non-inferiority margin was 10%. The required sample size was about 101 cases in each group. Based on the 10% dropout rate and the 10% propensity score matching failure rate, the required sample size was 120 cases in each group, and the total sample size was 240 cases. Patients were assigned according to their preferred type of treatment. In order to adjust for potential confounding factors, the propensity score was used to calculate the weight. The relevant factors included age, gender, BMI, preoperative ASA score, tumor location, tumor length, tumor width, single or multiple, depth of invasion, and vascular status. 4. Step 4.1 During the screening period, patients should complete imaging examination to exclude lymph node metastasis or distant metastasis, and provide ESD postoperative pathology (routine required). Eligible patients at each center were interviewed and provided written informed consent by a dedicated enrollment endoscopist, in accordance with the inclusion and exclusion criteria. The patient's age, gender, BMI, preoperative ASA score, tumor location, tumor length, tumor width, single or multiple, depth of invasion, and vascular status were collected. Patients were divided into experimental group or control group according to their wishes, and the quality of life was evaluated (required for the study). 4.2 During the selected treatment period, all surgical procedures or treatments were performed by one physician under the direct supervision of another medical staff engaged in clinical research activities. A control group of patients was collected during the enrollment treatment period: patients completed preoperative routine examinations including cardiopulmonary function, blood tests, and underwent esophagectomy one month after ESD. Patients were to undergo open esophagectomy, minimally invasive esophagectomy, or a combination of the two (McKeown or Ivor Lewis esophagectomy), with at least complete two-field lymph node dissection. The choice of surgical methods will be made by the surgeon according to the patient's condition, tumor size, location and other characteristics. According to the NCCN and 2022 CSCO guidelines for the diagnosis and treatment of esophageal cancer [5], at least 15 lymph nodes should be dissected, including lymph nodes at the upper thoracic para-esophagus, right recurrent laryngeal nerve, middle thoracic para-esophagus, lower thoracic para-esophagus, left recurrent laryngeal nerve, para-trachea, subcarinal, lower pulmonary ligament, diaphragm and other stations. Routine pathological examination was performed on the surgical specimens. In the experimental group, patients received concurrent chemoradiotherapy at 1 month after ESD. The regimen was as follows: on days 1, 8, 15, 22, and 29 (weekly cycle; 5 cycles) carboplatin (2 mg/ml/min area under the curve) and paclitaxel (50 mg/m2 body surface area); External beam radiotherapy was performed from the first day, once a day, 5 days a week, a total of 23 times, with a total dose of 41.4Gy, 1.8Gy each time. The medical history of the patients during the treatment was collected to understand the treatment and adverse events. 4.3 Follow-up period The follow-up period is 3 years according to the usual practice, and the specific plan is shown in the table below (the quality of life questionnaire is additional) : March June December 18 Month 24 Month 30 month 36 month Endoscopy √ √ √ √ √ √ √ Neck chest enhanced CT √ √ √ √ Quality of life questionnaire √ √ √ √ √ √ PET-CT √ √ √ √ Blood test √ √ √ √ √ √ √ √ √ Collected patient survival situation, Adverse event rates, endoscopic, CT, PET-CT findings, and quality-of-life questionnaire scores. Study End PointsPrimary end point was 3-year overall survival rate (OSR), defined as the proportion of patients who were still alive after 3 years of follow-up. The secondary end point was progress-free survival (PFS), defined as the proportion of patients who were still alive or progress-free after 3 years of follow-up, up to 36 months. Tumor progression was defined as radiographic or clinical deterioration. Non-in situ T1a ESCC detected by endoscopy can be curatively resected by endoscopic resection and is not classified as progressive. overall survival (OS) was defined as the time from enrollment to the last follow-up or death from any cause. progression free survival (PFS) was defined as the time from enrollment to the last follow-up, tumor progression, or death from any cause. Quality of life was assessed with the use of the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire C-30 (EORTC QLQ-C30) and the EORTC QLQ-OES18, which patients completed on the day of recruitment and at months 3, 6, 12, and 24 after treatment. 6. Clinical observation, follow-up and measures to ensure compliance of subjects Clinical observation: The relevant treatment and adverse events were recorded by clinicians in the hospital. Follow-up: the patients were followed up by telephone and outpatient visits. To ensure the compliance of the subjects, the enrolled patients must receive further treatment and regular follow-up to obtain long-term survival.

纳入标准：

Inclusion criteria

排除标准：

1) 同时或异时（5年内）恶性肿瘤个人史者； 2) 因严重心肺疾病、严重肾功能不全，无法耐受手术或放化疗患者； 3) 孕妇及哺乳期妇女； 4) 6个月内有心肌梗塞病史者； 5) 6个月内有脑梗死或脑出血病史者

Exclusion criteria：

1) personal history of synchronous or metachronous (within 5 years) malignant tumors; 2) patients who could not tolerate surgery or radiotherapy or chemotherapy due to severe heart and lung diseases or severe renal insufficiency; 3) pregnant and lactating women; 4) patients with a history of myocardial infarction within 6 months; 5) patients with a history of cerebral infarction or cerebral hemorrhage within 6 months

研究实施时间：

Study execute time：

从 From 2024-03-01 00:00:00至 To 2029-03-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2024-04-30 00:00:00 至 To 2027-03-31 00:00:00

干预措施：

Interventions：

组别：	同步放化疗组	样本量：	120
Group：	Simultaneous chemoradiotherapy group	Sample size：	120
干预措施：	同步放化疗	干预措施代码：
Intervention：	Simultaneous chemoradiotherapy	Intervention code：

组别：	外科手术组	样本量：	120
Group：	Surgery group	Sample size：	120
干预措施：	食管切除术	干预措施代码：
Intervention：	esophagectomy	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	上海市	市(区县)：
Country：	China	Province：	Shanghai	City：
单位(医院)：	复旦大学附属中山医院	单位级别：	三甲
Institution hospital：	Zhongshan Hospital, Fudan University	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	3年总体生存率	指标类型：	主要指标
Outcome：	overall survival rate	Type：	Primary indicator
测量时间点：	治疗结束后3年	测量方法：	存活情况随访
Measure time point of outcome：	3 years after the end of treatment	Measure method：	Survival follow-up

指标中文名：	3年无进展生存率	指标类型：	次要指标
Outcome：	progress-free survival	Type：	Secondary indicator
测量时间点：	治疗结束后3年	测量方法：	影像学与内镜随访
Measure time point of outcome：	3 years after the end of treatment	Measure method：	Imaging and endoscopic follow-up

指标中文名：	总生存期	指标类型：	次要指标
Outcome：	overall survival	Type：	Secondary indicator
测量时间点：	治疗结束后3年	测量方法：	存活情况随访
Measure time point of outcome：	3 years after the end of treatment	Measure method：	Survival follow-up

指标中文名：	无进展生存期	指标类型：	次要指标
Outcome：	progress-free survival	Type：	Secondary indicator
测量时间点：	治疗结束后3年	测量方法：	影像学与内镜随访
Measure time point of outcome：	3 years after the end of treatment	Measure method：	Imaging and endoscopic follow-up

指标中文名：	生活质量评价	指标类型：	次要指标
Outcome：	Life quality evaluation	Type：	Secondary indicator
测量时间点：	招募当天和治疗后的第3、6、12和24个月	测量方法：	欧洲癌症研究和治疗组织的生活质量问卷C-30（EORTC QLQ-C30）和EORTC QLQ-OES18
Measure time point of outcome：	On the day of recruitment and at 3, 6, 12 and 24 months after treatment	Measure method：	Quality of Life Questionnaire C-30 (EORTC QLQ-C30) and EORTC QLQ-OES18 of the European Organization for Research and Treatment of Cancer

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：	无	组织：
Sample Name：	none	Tissue：
人体标本去向	使用后销毁	说明
Fate of sample：	Destruction after use	Note：

征募研究对象情况：

Recruiting status：

尚未开始

Not yet recruiting

年龄范围：

Participant age：

最小 Min age	18	岁 years
最大 Max age	80	岁 years

性别：

男女均可

Gender：

Both

随机方法（请说明由何人用什么方法产生随机序列）：

无

Randomization Procedure (please state who generates the random number sequence and by what method)：

None

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

公开/Public

盲法：	无
Blinding：	None
试验完成后的统计结果（上传文件）：	点击下载
Calculated Results after the Study Completed(upload file)：	download

是否共享原始数据： IPD sharing	否No
共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：	无
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	None
数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：	使用EDC进行本研究的数据管理。 EDC的建库、数据采集、质量控制交由上海医药临床研究中心完成，质控访视每10例患者入组进行1次，并完成质控访视报告，数据核查每半年进行1次。完成患者入组后进行数据库锁库。
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	EDC was used for data management of this study. EDC database construction, data collection and quality control were completed by Shanghai Clinical Research Center for Medicine. Quality control visits were conducted once every 10 patients enrolled, and the report of quality control visits was completed. Database locking was performed after the completion of patient enrollment.
数据与安全监察委员会： Data and Safety Monitoring Committee：	有/Yes
注册人： Name of Registration：	2024-04-22 09:23:14