ChiCTR2400082243 版本V1.0 版本创建时间2024/03/25 11:50:22 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

ChiCTR2400082243 

最近更新日期：

Date of Last Refreshed on：

2024-03-25 11:50:18 

注册时间：

Date of Registration：

2024-03-25 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

局部晚期不可手术食管癌同步放化疗后特瑞普利单抗免疫巩固治疗的安全性和有效性研究

Public title：

Clinical study on the safety and efficacy of Toripalimab after concurrent chemoradiotherapy in patients with locally advanced, unresectable esophageal cancer

注册题目简写：

English Acronym：

研究课题的正式科学名称：

局部晚期不可手术食管癌同步放化疗后特瑞普利单抗免疫巩固治疗的安全性和有效性研究

Scientific title：

Clinical study on the safety and efficacy of Toripalimab after concurrent chemoradiotherapy in patients with locally advanced, unresectable esophageal cancer

研究课题代号(代码)：

Study subject ID：

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：

申请注册联系人：

周真珍 

研究负责人：

丁叔波 

Applicant：

Zhenzhen Zhou 

Study leader：

Shubo Ding 

申请注册联系人电话：

Applicant telephone：

+86 151 6795 6331

研究负责人电话：

Study leader's telephone：

+86 137 5098 3285

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：

zhouzhenzhen89@163.com

研究负责人电子邮件：

Study leader's E-mail：

jhyyys@163.com

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：

浙江省金华市婺城区人民东路365号

研究负责人通讯地址：

浙江省金华市婺城区人民东路365号

Applicant address：

No. 365, Renmin East Road, Wucheng District, Jinhua City, Zhejiang Province

Study leader's address：

No. 365, Renmin East Road, Wucheng District, Jinhua City, Zhejiang Province

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：

金华市中心医院

Applicant's institution：

Jinhua Municipal Central Hospital

研究负责人所在单位：

金华市中心医院

Affiliation of the Leader：

Jinhua Municipal Central Hospital

是否获伦理委员会批准：

是/Yes

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

(研)2023-伦理审查-73

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：

金华市中心医院伦理审查委员会

Name of the ethic committee：

Ethic Committee of Jinhua Municipal Central Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

2023-05-22 00:00:00

伦理委员会联系人：

季敬伟

Contact Name of the ethic committee：

Jinwe Ji

伦理委员会联系地址：

浙江省金华市婺城区人民东路365号

Contact Address of the ethic committee：

No. 365, Renmin East Road, Wucheng District, Jinhua City, Zhejiang Province

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 135 8865 6127

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：

金华市中心医院

Primary sponsor：

Jinhua Municipal Central Hospital

研究实施负责（组长）单位地址：

浙江省金华市婺城区人民东路365号

Primary sponsor's address：

No. 365, Renmin East Road, Wucheng District, Jinhua City, Zhejiang Province

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

浙江

市(区县)：

金华

Country：

China

Province：

Zhejiang

City：

Jinhua

单位(医院)：

金华市中心医院

具体地址：

浙江省金华市婺城区人民东路365号

Institution
hospital：

Jinhua Municipal Central Hospital

Address：

No. 365, Renmin East Road, Wucheng District, Jinhua City, Zhejiang Province

经费或物资来源：

科室

Source(s) of funding：

Department

Target disease：

esophageal cancer

Target disease code：

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：

单臂 

Study design：

Single arm 

研究目的：

中晚期食管癌放疗后5年生存率为8.0%-20%，治疗效果差。局部晚期食管癌的标准治疗方案为同步放化疗，但局部未控或复发是食管癌治疗失败的主要原因，提高放疗剂量或调整化疗方案无法提高晚期食管癌的生存率。目前免疫治疗是一种新型复杂的抗肿瘤治疗措施之一，主要通过调节自身免疫来促进免疫细胞对肿瘤细胞的杀伤，与放疗一起有协同作用。本研究旨在探索和确定不可切除局部晚期食管癌患者在同步放化疗后序贯特瑞普利单抗免疫巩固的治疗方法的安全性和有效性。  

Objectives of Study：

The 5-year survival rate after radiotherapy for advanced esophageal cancer is 8.0% -20%, and the treatment effect is poor. The standard treatment plan for locally advanced esophageal cancer is synchronous radiotherapy and chemotherapy, but uncontrolled or recurrent local conditions are the main reasons for treatment failure of esophageal cancer. Increasing the radiation dose or adjusting the chemotherapy regimen cannot improve the survival rate of advanced esophageal cancer. At present, immunotherapy is one of the new and complex anti-tumor treatment measures, which mainly promotes the killing of tumor cells by regulating autoimmunity of immune cells, and has a synergistic effect with radiotherapy. The aim of this study is to explore and determine the safety and effectiveness of sequential trepril monoclonal antibody immunoconsolidation therapy in patients with unresectable locally advanced esophageal cancer after synchronous radiotherapy and chemotherapy.

药物成份或治疗方案详述：

食管癌放疗总剂量PTV50.4-54Gy/28-30次，1.8Gy/次，放疗期间同步铂类+紫杉醇的方案每周方案化疗；放化疗结束后4周内开始给予特瑞普利单抗注射液200mg/次维持，每3周一次，维持一年或直至出现难以耐受的不良反应或疾病进展。 

Description for medicine or protocol of treatment in detail：

The total dose of radiotherapy for esophageal cancer is PTV50.4-54Gy/28-30 times, 1.8Gy/time. During the radiotherapy period, a weekly regimen of platinum plus paclitaxel chemotherapy is used; Within 4 weeks after the end of radiotherapy and chemotherapy, start administering 200mg/dose of Treprizumab injection for maintenance, every 3 weeks, for one year or until intolerable adverse reactions or disease progression occur. 

纳入标准：

1)所有受试者在开始研究相关操作前均需签署知情同意书; 2)所有患者年龄≥18岁且≤70岁; 3)组织学或细胞学证实的食管癌（鳞状细胞癌）; 4)临床分期为II-IVa期，经外科医生评估认为不可手术或患者拒绝手术; 5)AJCC第八版分期II-IVa期; 6)受试者根据RECIST1.1标准证实具有至少一个可测量病灶； 7)受试者既往未接受过任何针对食管癌的放、化疗、免疫治疗或生物治疗等抗肿瘤治疗; 8)ECOG PS 0~1分; 9)预计生存时间≥12周; 10)首次给药前14天内未输血及血制品，未使用G-CSF及其他造血刺激因子纠正; 11)首次给药在放疗完成的30天之内; 12)首剂研究药物前，实验室检查值满足以下条件： （1）血常规：WBC≥3.0×109/L；ANC≥1.5×109/L；PLT≥70×109/L； HGB≥9.0g/dL; （2）肝功能：无肝转移受试者AST≤2.5×ULN；ALT≤2.5×ULN，肝转移 受试者其ALT和 AST<5×ULN；TBIL≤1.5×ULN；ALB≥3g/dL; （3）肾功能：Cr≤1.5×ULN或CrCl≥40 mL/min；UPRO阴性; （4）凝血功能：INR≤1.5，APTT≤1.5×ULN; （5）其他：脂肪酶≤1.5×ULN，若脂肪酶>1.5×ULN无临床或影像学证实; 胰腺炎的情况可以入组；淀粉酶 ≤1.5×ULN，若淀粉酶>1.5×ULN无临床或影像学证实胰腺炎的情况可以入组; ALP≤2.5×ULN，骨转移受试者，ALP≤5×ULN。

Inclusion criteria

1) All participants are required to sign an informed consent form before starting the research related procedures; 2) All patients aged ≥ 18 years and ≤ 70 years; 3) Esophageal cancer confirmed by histology or cytology (squamous cell carcinoma); 4) The clinical stage is II-IVa, it is deemed inoperable by the surgeon or the patient refuses surgery; 5) AJCC Eighth Edition Phase II-IVa; 6) The subject confirmed to have at least one measurable lesion according to the RECIST 1.1 standard; 7) The subjects have not received any anti-tumor treatment such as radiotherapy, chemotherapy, immunotherapy, or biological therapy for esophageal cancer in the past; 8) ECOG PS 0-1 points; 9) Expected survival time ≥ 12 weeks; 10) No blood transfusion or blood products were received within 14 days before the first administration, and G-CSF and other hematopoietic stimulating factors were not used for correction; 11) The first administration is within 30 days after the completion of radiotherapy; 12) Before the first dose of the study drug, the laboratory test values meet the following conditions: (1) Blood routine: WBC ≥ 3.0 × 109/L; ANC ≥ 1.5 × 109/L; PLT ≥ 70 × 109/L; HGB ≥ 9.0g/dL; ; (2) Liver function: AST ≤ 2.5 × ULNin subjects without liver metastasis ; ALT ≤ 2.5 × ULN, Liver Metastasis Subject's ALT and AST<5 × ULN; TBIL ≤ 1.5 × ULN; ALB ≥ 3g/dL; (3) Renal function: Cr ≤ 1.5 × ULN or CrCl ≥ 40 mL/min; UPRO negative; (4) Coagulation function: INR ≤ 1.5, APTT ≤ 1.5 × ULN; (5) Other: Lipase ≤ 1.5 × ULN, if lipase>1.5 × ULN without clinical or imaging confirmation,Pancreatitis can be included in the group; Amylase ≤ 1.5 × ULN, if Amylase>1.5 × ULN can be included if there is no clinical or imaging confirmed pancreatitis; ALP ≤ 2.5 × ULN, bone metastasis subject, ALP ≤ 5 × ULN.

排除标准：

1)既往或同时患有其它未治愈的恶性肿瘤，已治愈的皮肤基底细胞癌、宫颈原位癌和浅表性膀胱癌除外； 2)病理提示为食管小细胞癌、腺癌或混合性癌; 3)食管原发灶与气管支气管、大血管关系紧密，研究者评估有较高的穿孔、大出血风险； 4)既往接受过任何T细胞共刺激或免疫检查点治疗，包括但不限于CTLA-4抑制剂、PD-1抑制剂、PD-L1/2抑制剂或其他靶向T细胞的药物; 5)在本次根治性放疗前，既往接收过其他胸部放射治疗的; 6)既往接受过抗VEGF或VEGFR治疗; 7)首剂研究药物前≤14天内使用皮质类固醇激素（>10mg/天强的松或等效剂量）或其他免疫抑制剂; 8)接受首剂研究药物前10天内使用阿司匹林（>325mg/天）或其他已知可以抑制血小板功能的非甾体抗炎药; 9)首次研究药物前两年内发生过自身免疫疾病，或患者患有免疫缺陷疾病; 10)间质性肺病、或重度的肺功能障碍; 11)首次研究药物前≤4周内接种过或计划接种活疫苗的受试者; 12)首剂研究用药前抗肿瘤治疗发生副反应CTCAE4.03≥2级并无法恢复到１级的受试者; 13)已知对药物或辅料过敏，已知对任何一种单抗发生严重过敏反应; 14)有重大的躯体或者心理方面的损伤不能保证放疗和免疫巩固治疗完整进行; 15)经研究者判断，受试者有其他可能导致本研究被迫中途终止的因素，如，不能定期随访、不依从方案、其他的严重疾病（含精神疾病）需要合并治疗，有严重的实验室检查异常，伴有家庭或社会等因素，会影响到受试者的安全，或资料及样品的收集； 16)放化疗后出现II级及以上放射性肺炎患者。

Exclusion criteria：

1) Previous or concurrent incurable malignant tumors, excluding cured skin Basal-cell carcinoma, cervical Carcinoma in situ and superficial bladder cancer; 2) Pathological findings were Small-cell carcinoma, adenocarcinoma or mixed carcinoma of the esophagus; 3) The primary focus of esophagus is closely related to tracheobronchial and Great vessels, and the researchers assess that there is a high risk of perforation and massive hemorrhage; 4) Previously received any T cell co stimulation or immune checkpoint therapy, including but not limited to CTLA-4 inhibitors, PD-1 inhibitors, PD-L1/2 inhibitors, or other drugs targeting T cells; 5) Prior to this radical radiotherapy, those who have received other chest radiation treatments in the past; 6) Previously received anti VEGF or VEGFR treatment; 7) Use Corticosteroid hormone (>10mg/day prednisone or Equivalent dose) or other Immunosuppressive drug ≤ 14 days before the first dose of study drug; 8) Use aspirin (>325 mg/day) or other Nonsteroidal anti-inflammatory drug known to inhibit platelet function within 10 days before receiving the first dose of study drug; 9) Have experienced autoimmune diseases within the two years prior to the first study of the drug, or have patients with immune deficiency diseases; 10) Interstitial lung disease, or severe pulmonary dysfunction; 11) Subjects who have received or plan to receive live vaccines within ≤ 4 weeks prior to the first study drug; 12) Subjects who experienced side effects of anti-tumor therapy before the first dose of study, CTCAE4.03 ≥ level 2, but were unable to recover to level 1; 13) Known to be allergic to drugs or excipients, and known to have severe allergic reactions to any type of monoclonal antibody; 14) Significant physical or psychological damage cannot guarantee the complete progress of radiotherapy and immune consolidation therapy; 15) According to the judgment of the researchers, the subjects may have other factors that may cause the study to be terminated midway, such as inability to follow up regularly, non-compliance with the protocol, other serious illnesses (including mental illness) requiring concurrent treatment, serious laboratory test abnormalities, accompanied by family or social factors, which may affect the safety of the subjects, or the collection of data and samples; 16) Patients with radiation pneumonia of grade II or above after radiotherapy and chemotherapy.

研究实施时间：

Study execute time：

从 From 2024-03-01 00:00:00至 To 2026-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2024-03-26 00:00:00 至 To 2026-12-31 00:00:00  

干预措施：

Interventions：

组别：

1

样本量：

20

Group：

1

Sample size：

干预措施：

同步放化疗后特瑞普利单抗免疫治疗

干预措施代码：

Intervention：

Toripalimab after concurrent chemoradiotherapy

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 浙江 

市(区县)：

 金华 

Country：

China 

Province：

Zhejiang 

City：

Jinhua 

单位(医院)：

金华市中心医院 

单位级别：

三甲 

Institution
hospital：

Jinhua Municipal Central Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

不良事件

指标类型：

主要指标

Outcome：

Adverse event

Type：

Primary indicator

测量时间点：

临床试验的受试者在签署知情同意书后出现任何不良的医学事件

测量方法：

Measure time point of outcome：

The subject of a clinical trial has any adverse medical event after signing the informed consent form

Measure method：

指标中文名：

严重不良事件

指标类型：

主要指标

Outcome：

Serious adverse event

Type：

Primary indicator

测量时间点：

临床试验过程中发生需要住院治疗或延长住院时间、伤残、影响工作能力、危及生命或死亡、导致先天畸形等医学事件

测量方法：

Measure time point of outcome：

In the course of clinical trials, medical events occur that require hospitalization or prolonged hospitalization, disability, affect work ability, endanger life or death, and lead to congenital malformations

Measure method：

指标中文名：

无进展生存期

指标类型：

次要指标

Outcome：

Progression free survival

Type：

Secondary indicator

测量时间点：

自随机至第一次影像学评估疾病进展(PD)或任何原因导致死亡的时间

测量方法：

Measure time point of outcome：

Time from randomization to the first radiographic assessment of disease progression (PD) or death from any cause

Measure method：

指标中文名：

客观有效率

指标类型：

次要指标

Outcome：

Objective response rate

Type：

Secondary indicator

测量时间点：

受试者自开始接受本研究治疗方案，至受试者疾病进展出组时，肿瘤缩小达到一定量并且保持一定时间的病人的比例，包含了CR和PR的病例

测量方法：

Measure time point of outcome：

The proportion of patients, including CR and PR cases, whose tumors had shrunk to a certain amount and remained there for a certain period of time from the time subjects began receiving treatment in the study to the time subjects progressed

Measure method：

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：

从随机到由于任何原因而死亡的时间

测量方法：

Measure time point of outcome：

From random to the time of death from any cause

Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

血液

组织：

食管

Sample Name：

Blood

Tissue：

esophagus

人体标本去向

 使用后销毁  

说明

使用后销毁

Fate of sample：

Destruction after use  

Note：

Destruction after use

征募研究对象情况：

Recruiting status：

正在进行

Recruiting

年龄范围：

Participant age：
最小 Min age 18 岁 years
最大 Max age 70 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：

Blinding：

试验完成后的统计结果（上传文件）：

Calculated Results after
the Study Completed(upload file)：

是否共享原始数据：

IPD sharing

Yes

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：

无

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：

none

数据与安全监察委员会：

Data and Safety Monitoring Committee：

暂未确定/Not yet

注册人：

Name of Registration：

  2024-03-25 11:50:18