ChiCTR2000032093 版本V1.5 版本创建时间2020/04/19 22:33:43 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：

ChiCTR2000032093 

最近更新日期：

Date of Last Refreshed on：

2020-04-19 22:32:47 

注册时间：

Date of Registration：

2020-04-19 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

PD-1（卡瑞利珠单抗）联合副干酪乳杆菌治疗晚期食管鳞状细胞癌的临床探索试验

Public title：

Clinical trial of PD-1 combined with Lactobacillus paracasei in the treatment of advanced esophageal squamous cell carcinoma

注册题目简写：

English Acronym：

研究课题的正式科学名称：

PD-1（卡瑞利珠单抗）联合副干酪乳杆菌治疗晚期食管鳞状细胞癌的临床探索试验

Scientific title：

Clinical trial of PD-1 combined with Lactobacillus paracasei in the treatment of 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：

马望 

研究负责人：

崔抗 

Applicant：

Ma Wang 

Study leader：

Cui Kang 

申请注册联系人电话：

Applicant telephone：

+86 13663846306

研究负责人电话：

Study leader's telephone：

+86 18339297220

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：

doctormawang@126.com

研究负责人电子邮件：

Study leader's E-mail：

776835179@qq.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：

河南省郑州市建设东路1号

研究负责人通讯地址：

河南省郑州市建设东路1号

Applicant address：

1 Jianshe Road East, Zhengzhou, He'nan, China

Study leader's address：

1 Jianshe Road East, Zhengzhou, He'nan, China

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：

郑州大学第一附属医院

Applicant's institution：

The First Affiliated Hospital of Zhengzhou University

研究负责人所在单位：

郑州大学第一附属医院

Affiliation of the Leader：

The First Affiliated Hospital of Zhengzhou University

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：

ss-2020-004

伦理委员会批件附件：

Approved file of Ethical Committee：

批准本研究的伦理委员会名称：

郑州大学第一附属医院国家药物临床试验机构

Name of the ethic committee：

National drug clinical trial institution of The First Affiliated Hospital of Zhengzhou University

伦理委员会批准日期：

Date of approved by ethic committee：

1990-01-01 00:00:00

伦理委员会联系人：

田丽

Contact Name of the ethic committee：

Tian Li

伦理委员会联系地址：

河南省郑州市建设东路1号

Contact Address of the ethic committee：

1 Jianshe Road East, Zhengzhou, He'nan, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

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：

郑州大学第一附属医院

Primary sponsor：

The First Affiliated Hospital of Zhengzhou University

研究实施负责（组长）单位地址：

河南省郑州市建设东路1号

Primary sponsor's address：

1 Jianshe Road East, Zhengzhou, He'nan, China

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

河南

市(区县)：

Country：

China

Province：

He'nan

City：

单位(医院)：

郑州大学第一附属医院

具体地址：

河南省郑州市建设东路1号

Institution
hospital：

The First Affiliated Hospital of Zhengzhou University

Address：

1 Jianshe Road East, Zhengzhou

经费或物资来源：

江苏恒瑞医药有限公司

Source(s) of funding：

Jiangsu Hengrui Pharmaceutical Co., Ltd

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：

 探索性研究/预试验 

Study phase：

0

研究设计：

非随机对照试验 

Study design：

Non randomized control 

研究目的：

探索卡瑞利珠单抗联合副干酪乳杆菌对晚期食管鳞状细胞癌的有效性和安全性。  

Objectives of Study：

To explore the efficacy and safety of carrizumab combined with Lactobacillus paracasei in the treatment of advanced esophageal squamous cell carcinoma

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)年龄18-75周岁的男性或女性；
2)经组织学或细胞学确诊的食管鳞状细胞癌，且局部晚期不可切除或伴远处转移；
3)副干酪乳杆菌可引起患者T细胞分泌γ-干扰素提高20%；
4)受试者为一线系统化疗或根治性同步放化疗治疗失败的患者。治疗失败的定义：接受一线系统化疗或根治性同步放化疗治疗期间或治疗后疾病进展，必须有影像学证据或临床证据证明疾病进展；对于新辅助/辅助治疗，如果在治疗期间或停止治疗后6个月内发生疾病进展，应将其算作一线治疗失败；
5)根据RECIST1.1至少有1处可评估的病灶，可测量病灶应未接受过放疗等局部治疗（位于既往放疗区域内的靶病灶，如果证实发生进展，并符合RECIST1.1标准，也可选做靶病灶）。
6)ECOG体力状况评分(ECOG-PS)：0~1。
7)重要器官的功能符合下列要求：
中性粒细胞计数(ANC)≥1.5×109/L；血红蛋白(Hb)≥90g/L；血小板计数≥75×109/L；血清白蛋白≥28g/l；胆红素≤1,5×正常上限（ULN）；总胆红素≤30mmol/L；天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)≤2.5倍ULN；若存在肝转移，则ALT、AST≤5倍ULN；
血清肌酐≤1.5×正常；淀粉酶和脂肪酶≤1.5ULN；INR的上限≤1.5；尿常规检查：尿蛋白<++或24小时尿蛋白定量≤1g。
8)心脏多普勒超声评估：左心室射血分数（LVEF）≥50%；
9)提供书面知情同意书愿意并能够遵守协议的所有方面；
10)具有生育能力的女性受试者应在接受首次研究药物前72小时内进行尿液或血清妊娠试验，并证明为阴性，并且愿意在试验期间至末次给予卡瑞利珠单抗后3个月内采取有效避孕。

Inclusion criteria

1. Male or female aged 18-75;
2. The patients with esophageal squamous cell carcinoma confirmed by histology or cytology and local advanced stage unresectable or with distant metastasis;
3. The secretion of IFN - γ by T cells increased by 20%;
4. Patients who failed to receive first-line systemic chemotherapy or radical synchronous radiotherapy and chemotherapy;
Definition of treatment failure: during or after the treatment of first-line systemic chemotherapy or radical synchronous radiotherapy and chemotherapy, there must be imaging evidence or clinical evidence to prove the disease progress; for neoadjuvant / adjuvant treatment, if the disease progress occurs during the treatment or within 6 months after the treatment is stopped, it should be regarded as first-line treatment failure;
5. Those patients who have at least one evaluable focus according to recist1.1 and have not received radiotherapy or other local treatment (target focus located in the previous radiotherapy area can also be selected as target focus if it is confirmed that it has progressed and meets recist1.1 standard);
6. Patients with ECOG-ps: 0-1;
7. Patients whose functions of important organs meet the following requirements:
Neutrophil count (ANC) ≥ 1.5 × 109 / L; hemoglobin (HB) ≥ 90g / L; platelet count ≥ 75 × 109 / L; serum albumin ≥ 28g / L; bilirubin ≤ 1,5 × upper normal limit (ULN); total bilirubin ≤ 30mmol / L; aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 times ULN; alt, AST ≤ 5 times ULN in the presence of liver metastasis;
Serum creatinine ≤ 1.5 × normal; amylase and lipase ≤ 1.5uln; upper limit of INR ≤ 1.5; routine urine test: urine protein < + + or 24-hour urine protein quantity ≤ 1g.
8. Doppler echocardiography: left ventricular ejection fraction (LVEF) ≥ 50%;
9. Patients who are willing and able to comply with the agreement by providing written informed consent;
10. Female subjects with fertility should be tested for urine or serum pregnancy within 72 hours before receiving the first study drug, which is proved to be negative, and they are willing to take effective contraception within 3 months from the test period to the last administration of carrizumab.

排除标准：

1)首次使用研究药物前4周内接受过抗肿瘤化疗、放疗、靶向小分子治疗，或者之前接受的药物所引起的不良事件尚未恢复（即须≤1级或达基线水平），注：≤2级神经病变或≤2级脱发的受试者除外，接受过大手术的患者，则在研究药物治疗之前其手术干预所造成的毒性反应和/或并发症必须充分恢复；
2)既往治疗（在纳入研究之前的6个月内）或目前正在使用其他益生菌治疗。
3)既往接受过针对PD-1/PD-L1的免疫治疗；
4)首次使用研究药物前的4周内接受过减毒活疫苗的受试者；
5)在1周内接受过任何原因的抗生素治疗；
6)首次使用研究药物前14天内，要求使用皮质类固醇（>10mg/天泼尼松疗效剂量）或其他免疫抑制剂进行系统治疗的受试者。在没有活动性自身免疫病的情况下，允许吸入或局部使用类固醇剂量>10mg/天泼尼松疗效剂量的肾上腺皮质激素替代；
7)有中枢神经系统转移的受试者；
8)既往有任何器官移植的受试者；
9)入组前1个月出现严重胃肠道出血或活动性咯血；
10)患有严重消化道吸收不良症及腹泻的受试者；
11)有活动性自身免疫病或自身免疫病病史的患者（如多发性硬化症，系统性红斑狼疮）。允许患有白癜风或脱发的受试者。允许患有牛皮癣、童年期哮喘的患者已完全缓解且无需任何干预，需要支气管扩张剂进行干预的哮喘患者不可纳入；
12)已有间质性肺病或活动性非感染性肺炎病史或证据；
13)患有未能控制的的心脏临床症状或疾病，如纽约心脏协会(NYHA)II级以上心力衰竭；不稳定心绞痛；在1年内发生过心肌梗死；有临床意义的室上性或室性心律失常需要临床干预的受试者；
14)在过去5年内发生的其他恶性肿瘤(经有效治疗的原位黑色素瘤、皮肤基底细胞癌、皮肤鳞状细胞癌、原位宫颈癌、原位乳腺癌除外)；
15)患有先天后后天免疫功能缺陷（如HIV感染者）、活动性乙肝（HBV-DNA≥104拷贝数/ml）或丙肝（丙肝抗体阳性，且HCV-DNA高于分析方法的检测下限）；
16)有活动性感染，或在筛选期间，首次给药前发生原因不明发热>38.5℃（经研究者判断，受试者因肿瘤产生的发热可以入组）；
17)已知对任何卡瑞利珠单抗或副干酪乳杆菌制剂任何成分过敏；
18)首次使用研究药物前4周或正在参与其他临床试验；
19)怀孕或哺乳期的妇女；
经研究者判断，受试者有其他可能导致其被迫终止研究的因素，如患有其他严重疾病需要合并治疗，实验室检查值严重异常，家庭或社会因素，可能影响到受试者安全或试验资料收集的情况。

Exclusion criteria：

1. Patients who have received anti-tumor chemotherapy, radiotherapy, targeted small molecule therapy or the adverse events caused by the previously received drugs within 4 weeks before the first use of the study drug have not recovered (i.e., must be ≤ level 1 or reach the baseline level), except for the subjects with grade 2 neuropathy or grade 2 alopecia. For patients undergoing major surgery, the toxicity and / or complications caused by surgical intervention must be fully recovered before the study drug treatment;
2. Patients with a previous treatment history (within 6 months prior to inclusion in the study) or who are currently using other probiotic treatments.
3. Patients who have previously received immunotherapy for PD-1 / PD-L1;
4. Subjects who received live attenuated vaccine within 4 weeks before the first use of the study drug;
5. Patients who received antibiotic treatment for any reason within one week;
6. Subjects who required systematic treatment with corticosteroids (> 10mg / day of prednisone) or other immunosuppressants within 14 days before the first use of the study drug. In the absence of active autoimmune disease, it is allowed to inhale or topically use corticosteroids with a therapeutic dose of > 10mg / day prednisone;
7. Subjects with central nervous system metastasis;
8. Subjects with any previous organ transplantation;
9. Patients with severe gastrointestinal bleeding or active hemoptysis 1 month before admission;
10. Subjects with severe gastrointestinal malabsorption and diarrhea;
11. Patients with a history of active autoimmune disease or autoimmune disease (such as multiple sclerosis, systemic lupus erythematosus). Subjects with vitiligo or alopecia were allowed. Patients with psoriasis and childhood asthma who have been completely relieved and do not need any intervention can be included;
12. Patients with history or evidence of interstitial lung disease or active noninfective pneumonia;
13. Patients with uncontrolled clinical symptoms or diseases of the heart, such as NYHA class II or above heart failure, unstable angina, myocardial infarction within one year, clinically significant supraventricular or ventricular arrhythmia, need clinical intervention;
14. Patients with other malignant tumors in the past 5 years (except for melanoma in situ, basal cell carcinoma of skin, squamous cell carcinoma of skin, cervical carcinoma in situ, breast carcinoma in situ, which have been effectively treated);
15. Patients with acquired immune deficiency (such as HIV infected patients), active hepatitis B (HBV-DNA ≥ 104 copies / ml) or hepatitis C (HCV antibody positive, and hcv-dna higher than the detection limit of the analysis method) after the first day;
16. Patients with active infection or unknown fever > 38.5 ℃ before the first administration during the screening period (according to the judgment of the researcher, the fever caused by tumor can be included in the group);
17. Objects known to be allergic to any of the ingredients of any of the clarizumab or Lactobacillus paracasei preparations;
18. Subjects participating in other clinical trials 4 weeks before the first use of the study drug;
19. Pregnant or lactating women;
According to the researcher's judgment, there are other factors that may cause the subject to be forced to terminate the study, such as suffering from other serious diseases requiring combined treatment, severe laboratory test value abnormality, family or social factors, which may affect the safety of the subject or the collection of test data.

研究实施时间：

Study execute time：

从 From 2020-04-01 00:00:00至 To 2021-04-01 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2020-04-25 00:00:00 至 To 2021-04-01 00:00:00  

干预措施：

Interventions：

组别：

干预组

样本量：

20

Group：

干预组 Intervention group

Sample size：

干预措施：

卡瑞利珠单抗联合益生菌

干预措施代码：

Intervention：

Prebiotics combined with carbarizumab

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 河南 

市(区县)：

  

Country：

china 

Province：

henan 

City：

 

单位(医院)：

郑州大学第一附属医院 

单位级别：

三级甲等 

Institution
hospital：

The First Affiliated Hospital of Zhengzhou University

Level of the institution：

Tertiary A hospital

测量指标：

Outcomes：

指标中文名：

无进展生存期

指标类型：

主要指标

Outcome：

PFS

Type：

Primary 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：

血液

组织：

Sample Name：

Blood

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：

正在进行

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）：

随机单臂

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

Random single arm

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）：

试验完成后6个月内公开

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

The data will be disclosed within six months after completion of the study

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：

edc

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

edc

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2020-04-19 21:49:21