ChiCTR2100055096 版本V1.3 版本创建时间2022/07/15 21:56:02 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：

ChiCTR2100055096 

最近更新日期：

Date of Last Refreshed on：

2022-07-15 21:52:17 

注册时间：

Date of Registration：

2021-12-31 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

同步放化疗联合PD-1单抗治疗局部晚期食管鳞状细胞癌前瞻性、多中心、随机、双盲、安慰剂对照临床研究

Public title：

A prospective, multi-center, randomized, double-blind, placebo-controlled clinical study of concurrent radiotherapy and chemotherapy combined with PD-1 monoclonal antibody in the treatment of locally advanced esophageal squamous cell carcinoma

注册题目简写：

English Acronym：

研究课题的正式科学名称：

同步放化疗联合PD-1单抗治疗局部晚期食管鳞状细胞癌前瞻性、多中心、 随机、双盲、安慰剂对照临床研究

Scientific title：

A prospective, multi-center, randomized, double-blind, placebo-controlled clinical study of concurrent radiotherapy and chemotherapy combined with PD-1 monoclonal antibody in the treatment of locally advanced esophageal squamous cell carcinoma

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：

吕家华 

研究负责人：

李涛 

Applicant：

Lyu Jiahua 

Study leader：

Li Tao 

申请注册联系人电话：

Applicant telephone：

+86 17713539529

研究负责人电话：

Study leader's telephone：

+86 18908178818

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：

winlttljh@163.com

研究负责人电子邮件：

Study leader's E-mail：

litaoxmf@126.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：

四川省成都市武侯区人民南路四段55号

研究负责人通讯地址：

四川省成都市武侯区人民南路四段55号

Applicant address：

55 the Fourth Section of Renmin Road South, Wuhou District, Chengdu, Sichuan

Study leader's address：

55 the Fourth Section of Renmin Road South, Wuhou District, Chengdu, Sichuan

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：

四川省肿瘤医院

Applicant's institution：

Sichuan Cancer Hospital

研究负责人所在单位：

Affiliation of the Leader：

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：

SCCHEC-02-2021-097

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：

四川省肿瘤医院医学科研与医疗新技术伦理委员会

Name of the ethic committee：

Ethics Committee of Medical Research and New Medical Technology of Sichuan Cancer Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

2021-12-21 00:00:00

伦理委员会联系人：

张国楠

Contact Name of the ethic committee：

Zhang Guonan

伦理委员会联系地址：

四川省成都市武侯区人民南路四段55号

Contact Address of the ethic committee：

55 the Fourth Section of Renmin Road South, Wuhou District, Chengdu, Sichuan

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 28 85420681

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：

四川省肿瘤医院

Primary sponsor：

Sichuan Cancer Hospital

研究实施负责（组长）单位地址：

四川省成都市武侯区人民南路四段55号

Primary sponsor's address：

55 the Fourth Section of Renmin Road South, Wuhou District, Chengdu, Sichuan

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

四川

市(区县)：

成都

Country：

China

Province：

Sichuan

City：

Chengdu

单位(医院)：

四川省肿瘤医院

具体地址：

武侯区人民南路四段55号

Institution
hospital：

Sichuan Cancer Hospital

Address：

55 the Fourth Section of Renmin Road South, Wuhou District

经费或物资来源：

四川省肿瘤医院-临床科学家研究计划

Source(s) of funding：

Sichuan Cancer Hospital-Clinical Scientist Research Program

Target disease：

Locally advanced esophageal squamous cell carcinoma

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 上市后药物 

Study phase：

4

研究设计：

随机平行对照 

Study design：

Parallel 

研究目的：

比较信迪利单抗联合 cCRT 与安慰剂联合 cCRT 在 ITT 分析集中的无进展生存期（PFS）。  

Objectives of Study：

Compare the progression-free survival (PFS) of Sintilimab combined with cCRT and placebo combined with cCRT in the ITT analysis set.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

1.患者或患者的法定代理人能够签署书面知情同意书，并能理解和同意遵循研究要求；
2.签署知情同意书时年龄介于18至75岁之间；
3.经组织学确诊为局部晚期ESCC，且适合进行CCRT，包括:II-IVa期（AJCC第8版[Rice等，2017]）无法手术的ESCC患者（医学上不适合手术或拒绝手术）及分期为M1且仅有锁骨上淋巴结转移的ESCC患者；
4.存在符合RECISTv1.1定义的可测量和/或不可测量病灶；
5.ECOG体能状态≤1；
6.器官功能良好，指在入组前14天内获得的实验室检查指标如下：
（1）患者在筛选期样本采集前≤14天内无需输血或生长因子治疗便可达到以下指标：绝对中性粒细胞计数（ANC）≥1.5×10^9/L，血小板≥100×10^9/L，血红蛋白≥90g/L；
（2）血清肌酐≤1.5×ULN（正常范围上限），或通过慢性肾脏病流行病学协作组方程；
（3）（附录9）估算的肾小球滤过率≥60mL/min/1.73m^2；
（4）血清总胆红素≤1.5×ULN（吉尔伯特综合征患者的总胆红素必须≤3×ULN）；
（5）天门冬氨酸氨基转移酶和ALT＜3×ULN；
7.非活动性/无症状携带者、慢性或活动性 HBV 患者的指标必须符合：筛选期HBV 脱氧核糖核酸（DNA）＜500IU/mL（或2500拷贝/mL）；
注：应根据治疗指南对乙型肝炎表面抗原阳性或 HBVDNA阳性的患者进行管理。在筛选期接受抗病毒药物治疗的患者应在入组前接受了>2周的治疗。
8.有生育能力的女性须自愿在研究期间以及末次信迪利单抗给药后≥120天内采取高效避孕措施，并且入组前≤7天内尿液或血清妊娠检验结果为阴性；
9.未绝育的男性受试者须自愿在研究期间以及末次信迪利单抗给药后≥120天内采取高效避孕措施。

Inclusion criteria

1. The patient or the patient's legal representative can sign a written informed consent form, and can understand and agree to follow the research requirements;
2. Aged between 18 and 75 years when signing the informed consent;
3. Histologically confirmed locally advanced ESCC and suitable for CCRT, including: Stage II-IVa (AJCC 8th edition [Rice et al, 2017]) inoperable ESCC patients (medically ineligible for surgery or refusing surgery) and ESCC stage M1 patients with only supraclavicular lymph node metastases;
4. There are measurable and/or unmeasurable lesions that meet the definition of RECISTv1.1;
5. ECOG fitness status<=1;
6. Good organ function, which means the laboratory test indicators obtained within 14 days before enrollment are as follows:
(1) The patient can achieve the following indicators without blood transfusion or growth factor treatment within <=14 days before sample collection in the screening period: absolute neutrophil count (ANC) >=1.5x10^9/L, platelets>=100x10^9/L, hemoglobin>=90g/L;
(2) Serum creatinine <= 1.5xULN (upper limit of normal range), or through the Chronic Kidney Disease Epidemiology Collaborative Group equation;
(3) (Appendix 9) estimated glomerular filtration rate >=60mL/min/1.73m^2;
(4) Serum total bilirubin <=1.5xULN (total bilirubin in patients with Gilbert syndrome must be <=3xULN);
(5) Aspartate aminotransferase and ALT<3xULN;
7. The indicators of inactive/asymptomatic carriers, chronic or active HBV patients must meet: HBV deoxyribonucleic acid (DNA) <500IU/mL (or 2500 copies/mL) during the screening period;
NOTE: Patients who are HBsAg-positive or HBVDNA-positive should be managed according to treatment guidelines. Patients receiving antiviral medication during the screening period should have received >2 weeks of treatment prior to enrollment.
8. Females of childbearing potential must voluntarily take high-efficiency contraceptive measures during the study period and within >= 120 days after the last dose of sintilimab, and the urine or serum pregnancy test results are negative within <= 7 days before enrollment;
9. Unsterilized male subjects must voluntarily take high-efficiency contraception during the study period and within >= 120 days after the last sintilimab administration.

排除标准：

1.具有原发性肿瘤浸润引起瘘管的病史；
2.有食管瘘高风险或食管穿孔征象的患者；
3.存在远端转移证据（M1疾病 AJCC第8版；
4.食管癌手术史；
5.有重度营养不良的指征；
6.存在临床上未控制的、需要反复引流或医疗干预（在随机分组前2周内）的胸腔积液、心包积液或腹水；
7.已知对试验方案中指定的化疗不耐受或耐药；
8.曾接受过放疗、化疗、靶向治疗、食管手术治疗或抗PD-1、PD-L1、PD-L2治疗或其他肿瘤免疫治疗；
9.有活动性自身免疫性疾病或者有自身免疫性疾病史但可能复发的患者注：以下疾病的患者不排除，可以进入进一步筛选：
（1）可控的I 型糖尿病；
（2）甲状腺功能减退（仅采用激素替代疗法便可控制）；
（3）可控的乳糜泻；
（4）无需全身治疗的皮肤病（如白癜风、银屑病、脱发）；
（5）如无外部诱因则预期不会复发的任何其他疾病；
10.除本研究正在研究的特定癌症和已经治愈的局部复发性癌症（如，经过切除的基底细胞或鳞状细胞皮肤癌、浅表性膀胱癌、宫颈或乳腺原位癌）外，在入组前≤2年存在其他活动性恶性肿瘤；
11.在随机之前≤14天内有任何需要用皮质类固醇（剂量>10mg/日的强的松或等效剂量的同类药物）或其它免疫抑制剂全身治疗的病症；
注：目前或之前曾使用过以下任何类固醇方案的患者不被排除：
（1）肾上腺素替代性类固醇（强的松≤10mg/日或等效剂量的同类药物）；
（2）全身吸收量极小的局部、眼用、关节内、鼻内或吸入性皮质类固醇；
（3）预防性地短期（≤7天）使用皮质类固醇（例如，预防造影剂过敏）或用于治疗非自身免疫病症（例如由接触过敏原引起的迟发性超敏反应）；
12.入组前≤14天，存在未控制的糖尿病、尽管进行了标准药物治疗仍>1级的钾、钠或校正钙实验室检查值异常或≥3级的低白蛋白血症；
13.具有间质性肺病病史、非感染性肺炎或未控制的全身性疾病，包括肺纤维化、急性肺部疾病等；
14.在入组前14天内存在需全身抗菌治疗、抗真菌治疗或抗病毒治疗的重度慢性或活动性感染（包括结核感染等）；
15.已知有 HIV 感染史；
16.入组前≤28天进行过大手术；
注：微创手术（比如经外周静脉穿刺中心静脉置管[PICC]）不属于大手术。
17.接受过异基因干细胞移植或器官移植；
18.存在以下任一心血管风险因素：
（1）在入组前≤28天内出现心源性胸痛，定义为限制日常生活器具性活动的中度疼痛；
（2）在入组前≤28天内出现症状性肺栓塞；
（3）在入组前≤6个月内曾发生急性心肌梗死；
（4）在入组前≤6个月内有达到纽约心脏病协会III 或IV 级（附录7）的心力衰竭病史；
（5）在入组前≤6个月内曾发生≥2级的室性心律失常事件；
（6）在入组前≤6个月内曾发生脑血管意外；
（7）在入组前≤28天，尽管使用降压药物仍未控制的高血压，即收缩压≥160mmHg 或舒张压≥100mmHg；
（8）在入组前≤28天出现晕厥或癫痫发作；
19.对其他单克隆抗体或顺铂或紫杉醇有严重超敏反应病史；
20.在研究药物首次给药前14天或5个半衰期内（以较短者为准），曾接受过任何化疗、免疫治疗（例如白介素、干扰素、胸腺素）或任何研究治疗；
21.在研究药物首次给药前14天内服用过控制癌症的草药；
22.既往抗肿瘤治疗导致的毒副作用尚未恢复到基线或稳定水平的患者，除非被认为是不可能带来安全性风险的AE（例如，脱发、神经病变、特定的实验室检查值异常）；
23.在入组前≤28天接种过活疫苗；
注：季节性流感疫苗通常是灭活疫苗，允许使用。鼻内疫苗是活疫苗，不允许使用。
24.存在不利于研究药物给药，或对药物毒性或AE解释有影响，或者会导致受试者执行研究的依从性降低或受影响的基础疾病（包括实验室检查值异常）、酒精或药物滥用或依赖；
25.同时参加另一项治疗性临床试验。

Exclusion criteria：

1. A history of fistula caused by primary tumor infiltration;
2. Patients with high risk of esophageal fistula or signs of esophageal perforation;
3. Evidence of distant metastasis (M1 disease AJCC 8th edition;
4. History of esophageal cancer surgery;
5. There are indications of severe malnutrition;
6. There is clinically uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage or medical intervention (within 2 weeks before randomization);
7. Known intolerance or resistance to chemotherapy specified in the trial protocol;
8. Received radiotherapy, chemotherapy, targeted therapy, esophageal surgery or anti-PD-1, PD-L1, PD-L2 therapy or other tumor immunotherapy;
9. Patients with active autoimmune disease or a history of autoimmune disease but may relapse Note: Patients with the following diseases are not excluded and can enter further screening:
(1) Controllable type I diabetes;
(2) Hypothyroidism (which can be controlled only with hormone replacement therapy);
(3) Controllable celiac disease;
(4) Skin diseases that do not require systemic treatment (such as vitiligo, psoriasis, alopecia);
(5) Any other disease that is not expected to recur if there is no external inducement;
10. Except for the specific cancers being studied in this study and locally recurrent cancers that have been cured (eg, resected basal cell or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast), other active malignancies <= 2 years prior to enrollment;
11. Any disease requiring systemic treatment with corticosteroids (dose >10 mg/day prednisone or equivalent doses of similar drugs) or other immunosuppressive agents within <= 14 days prior to randomization;
NOTE: Patients who are currently or have previously used any of the following steroid regimens are not excluded:
(1) Adrenaline replacement steroids (prednisone <= 10mg/day or equivalent doses of similar drugs);
(2) Topical, ophthalmic, intra-articular, intranasal or inhaled corticosteroids with minimal systemic absorption;
(3) Prophylactic short-term (<=7 days) use of corticosteroids (for example, to prevent contrast agent allergy) or for the treatment of non-autoimmune conditions (such as delayed hypersensitivity reactions caused by exposure to allergens);
12. <=14 days before enrollment, there is uncontrolled diabetes, and despite standard drug treatment, potassium, sodium or corrected calcium laboratory test values are > 1 abnormal or >= 3 hypoalbuminemia;
13. History of interstitial lung disease, non-infectious pneumonia or uncontrolled systemic disease, including pulmonary fibrosis, acute lung disease, etc.;
14. Severe chronic or active infection (including tuberculosis infection, etc.) requiring systemic antibacterial, antifungal or antiviral treatment within 14 days before enrollment;
15. Known history of HIV infection;
16. Major surgery <= 28 days before enrollment;
Note: Minimally invasive procedures (eg, Peripheral Puncture Central Catheter [PICC]) are not considered major surgery.
17. Received allogeneic stem cell transplantation or organ transplantation;
18. Presence of any of the following cardiovascular risk factors:
(1) Cardiogenic chest pain within <= 28 days prior to enrollment, defined as moderate pain that restricts instrumental activities of daily living;
(2) Symptomatic pulmonary embolism occurred within <=28 days before enrollment;
(3) Acute myocardial infarction occurred within <=6 months before enrollment;
(4) A history of heart failure reaching New York Heart Association Class III or IV (Appendix 7) within <=6 months before enrollment;
(5) A ventricular arrhythmia event of grade >= 2 occurred within <= 6 months before enrollment;
(6) Cerebrovascular accident occurred within <=6 months before enrollment;
(7) Hypertension that is not controlled despite the use of antihypertensive drugs within <=28 days before enrollment, that is, systolic blood pressure >=160 mmHg or diastolic blood pressure >=100 mmHg;
(8) Syncope or epilepsy occurred <=28 days before enrollment;
19. History of severe hypersensitivity reactions to other monoclonal antibodies or cisplatin or paclitaxel;
20. Received any chemotherapy, immunotherapy (such as interleukin, interferon, thymosin) or any study treatment within 14 days or 5 half-lives (whichever is shorter) before the first administration of the study drug;
21. Taking herbal medicines for cancer control within 14 days before the first administration of the study drug;
22. Patients whose toxic and side effects caused by previous anti-tumor therapy have not returned to baseline or stable levels, unless they are considered AEs that are unlikely to pose a safety risk (eg, alopecia, neuropathy, abnormal specific laboratory test values);
23. Received live vaccine <=28 days before enrollment;
Note: Seasonal influenza vaccines are usually inactivated vaccines and are permitted. Intranasal vaccines are live vaccines and are not allowed.
24. There is an underlying disease (including abnormal laboratory test values) that is not conducive to the administration of the study drug, or has an impact on the interpretation of drug toxicity or AE, or will lead to a decrease in the subject's compliance with the study or to be affected, alcohol or drug abuse or dependence;
25. Participate in another therapeutic clinical trial at the same time.

研究实施时间：

Study execute time：

从 From 2022-02-01 00:00:00至 To 2026-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2022-02-01 00:00:00 至 To 2024-02-01 00:00:00  

干预措施：

Interventions：

组别：

试验组

样本量：

134

Group：

Experimental group

Sample size：

干预措施：

信迪利单抗+化疗+放疗（同步）

干预措施代码：

Intervention：

Sintilimab + chemotherapy + radiotherapy (simultaneous)

Intervention code：

组别：

对照组

样本量：

134

Group：

Control group

Sample size：

干预措施：

安慰剂+化疗+放疗（同步）

干预措施代码：

Intervention：

Placebo + chemotherapy + radiotherapy (concurrent)

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 四川 

市(区县)：

 成都 

Country：

China 

Province：

Sichuan 

City：

Chengdu 

单位(医院)：

四川省肿瘤医院 

单位级别：

三甲 

Institution
hospital：

Sichuan Cancer Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

无进展生存时间

指标类型：

主要指标

Outcome：

Progression-free survival

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

客观缓解率

指标类型：

次要指标

Outcome：

Objective response rate

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

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：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

健康相关生命质量

指标类型：

次要指标

Outcome：

Health-related quality of life

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

新鲜肿瘤组织

组织：

Sample Name：

Fresh tumor tissue

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 75 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）：

研究中心工作人员用IRT系统产生随机分配

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

The staff of the research center use the IRT system to generate random assignments

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

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）：

研究者处获取

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：

Get from researchers

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：

病例记录表

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

Case Record Form, CRF

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2021-12-31 23:19:42