ChiCTR2100047129 版本V3.0 版本创建时间2022/01/23 22:22:26 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：

ChiCTR2100047129 

最近更新日期：

Date of Last Refreshed on：

2022-01-23 22:12:25 

注册时间：

Date of Registration：

2021-06-08 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

靶向EpCAM的嵌合抗原受体修饰的自体T细胞用于晚期胃癌的临床研究

Public title：

EpCAM-targeted chimeric antigen receptor modified autologous T cells for clinical research of advanced gastric cancer

注册题目简写：

English Acronym：

研究课题的正式科学名称：

靶向EpCAM的嵌合抗原受体修饰的自体T细胞用于晚期胃癌的临床研究

Scientific title：

EpCAM-targeted chimeric antigen receptor modified autologous T cells for clinical research of advanced gastric 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：

唐芳 

研究负责人：

卢正茂 

Applicant：

Tang Fang 

Study leader：

Lu Zhengmao 

申请注册联系人电话：

Applicant telephone：

+86 13651881093

研究负责人电话：

Study leader's telephone：

+86 21 50907211

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：

183799410@qq.com

研究负责人电子邮件：

Study leader's E-mail：

luzhengmao1982@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：

上海市杨浦区长海路168号

研究负责人通讯地址：

上海市杨浦区长海路168号

Applicant address：

168 Changhai Road, Yangpu District, Shanghai

Study leader's address：

168 Changhai Road, Yangpu 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：

上海市长海医院

Applicant's institution：

Shanghai Changhai Hospital

研究负责人所在单位：

上海市长海医院

Affiliation of the Leader：

Shanghai Changhai 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：

CHEC2021-68

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：

上海长海医院伦理委员会

Name of the ethic committee：

Shanghai Changhai Hospital Ethics Committee

伦理委员会批准日期：

Date of approved by ethic committee：

2021-05-21 00:00:00

伦理委员会联系人：

罗天航

Contact Name of the ethic committee：

Luo Tianhang

伦理委员会联系地址：

上海市杨浦区长海路168号

Contact Address of the ethic committee：

168 Changhai Road, Yangpu District, Shanghai

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：

上海长海医院

Primary sponsor：

Shanghai Changhai Hospital

研究实施负责（组长）单位地址：

上海市杨浦区长海路168号

Primary sponsor's address：

168 Changhai Road, Yangpu District, Shanghai

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(区县)：

杨浦区

Country：

China

Province：

Shanghai

City：

Yangpu District

单位(医院)：

上海长海医院

具体地址：

长海路168号

Institution
hospital：

Shanghai Changhai Hospital

Address：

168 Changhai Road

经费或物资来源：

科研基金会

Source(s) of funding：

Research Foundation

Target disease：

advanced gastric 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：

单臂 

Study design：

Single arm 

研究目的：

主要目的： 1.对晚期胃癌患者进行IMC001的静脉滴注治疗，观察和评估患者的安全性、耐受性。 次要目的： 1.对晚期胃癌患者进行IMC001的治疗，根据剂量限制毒性和临床反应情况包括可能的副作用情况，来确定最大耐受剂量并为临床I-II期治疗提供计划及剂量方案； 2.评估IMC001的药效学（PD）生物标志物与临床疗效的相关性；IMC001在体内扩增和持续性及药效学（PD）生物标志物与不良事件之间的相关性； 3.评估晚期胃癌患者使用IMC001的初步抗肿瘤疗效。根据实体瘤疗效评价标准（RECIST）V.1.1版、实体瘤免疫治疗疗效评价标准（iRECIST），采用客观缓解率（ORR）、缓解持续时间（DOR）、疾病控制率（DCR）和无进展生存期（PFS）描述初步抗肿瘤活性； 4.与治疗相关的不良反应事件发生率。  

Objectives of Study：

Main purpose: 1.Carry out IMC001 intravenous drip treatment for patients with advanced gastric cancer, observe and evaluate the safety and tolerability of patients. Secondary purpose: 1.Treat patients with advanced gastric cancer with IMC001, and determine the maximum tolerated dose according to dose-limiting toxicity and clinical response, including possible side effects, and provide a plan and dosage regimen for clinical phase I-II treatment; 2.Assess the correlation between the pharmacodynamic (PD) biomarkers of IMC001 and clinical efficacy; the expansion and persistence of IMC001 in vivo and the correlation between the pharmacodynamic (PD) biomarkers and adverse events; 3.To evaluate the preliminary anti-tumor efficacy of IMC001 in patients with advanced gastric cancer. According to the Curative Effect Evaluation Standard for Solid Tumors (RECIST) Version V.1.1 and the Evaluation Standard for Immunotherapy Curative Effect for Solid Tumors (iRECIST), objective response rate (ORR), duration of response (DOR), disease control rate (DCR) and progression-free survival are adopted Phase (PFS) describes the preliminary anti-tumor activity; 4.Incidence of treatment-related adverse events.

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.年龄介于18~70岁（包括边界值），男女均可；
2.既往接受过二线及以上治疗失败的局晚期胃癌及转移性胃癌患者，没有其他可行的有效治疗手段，受试者的预计生存周期>=12周；
(1)治疗失败的定义为：治疗过程中发生不可耐受的毒性反应或疾病进展或治疗结束后肿瘤复发或转移；
(2)每线治疗用药时间>=1个周期或更长时间的一种或多种化疗药物；允许早期进行辅助/新辅助治疗，如果辅助/新辅助治疗期间或完成后<=24周内发展肿瘤复发和转移，则认为前期的辅助/新辅助治疗是全身化疗；
(3)允许前期治疗为靶向药物、免疫抑制剂或放疗；
(4)允许前期治疗是化疗联合靶向药物。
3.按照RECISTv 1.1标准，受试者拥有至少1个可稳定评估的靶病灶；
4.活检肿瘤组织样本EpCAM组织学染色阳性；
5.ECOG体力状态评分0~1；
6.受试者有足够的器官和骨髓功能。实验室筛查必须满足以下标准（参照NCI CTC AE 5.0）所有的实验室检测检测结果应当在下述稳定范围内，且没有持续性支持治疗；
(1)血液检查：白细胞WBC>= 1.5x10^9/L；血小板计数PLT >=60x10^9/L；血红蛋白含量Hb >=8.0g/dL；淋巴细胞LYM>=0.4x10^9/L；
(2)血液生化：血清肌酐<=1.5xULN, 如血清肌酐>1.5xULN，肌酐清除率需>50mL/min（根据Cockcroft-Gault公式计算）；血清总胆红素<=1.5xULN，丙氨酸氨基转移酶(ALT)<=2 xULN；天门冬氨酸氨基转移酶(AST)<=2 xULN（肝转移或肝癌患者ALT<=5xULN，AST<=5xULN）；
(3)淀粉酶和脂肪酶<= 1.5 x ULN；
(4)尿常规检查：尿蛋白< 2+。
7.一个月内心脏彩超检查左心室射血分数（LVEF）>45%；
8.生育状态：育龄期女性患者或性伴侣为育龄期女性的男性患者，愿意从签署知情同意书开始至末次细胞输注后6个月内采取有效避孕措施；育龄期女性包括绝经前女性和绝经后2年内的女性。受试者必须同意在治疗期间遵守避孕指导；
9.受试者必须签署书面知情同意书并注明日期；
10.受试者必须自愿并且能够依从预定治疗方案、实验室检查、随访及其他研究要求。

Inclusion criteria

1.Aged 18 to 70 years (including boundary value), both male and female;
2.Patients with locally advanced gastric cancer and metastatic gastric cancer who have failed second-line or above treatments in the past have no other feasible effective treatments, and the expected survival period of the subjects is >=12 weeks;
(1)Treatment failure is defined as: the occurrence of intolerable toxicity or disease progression during treatment or tumor recurrence or metastasis after the end of treatment;
(2)One or more chemotherapeutics with each line of treatment for >=1 cycle or longer; early adjuvant/neo-adjuvant therapy is allowed, if tumor recurrence develops during or <=24 weeks after completion of adjuvant/neo-adjuvant therapy And metastasis, the previous adjuvant/neo-adjuvant therapy is considered systemic chemotherapy;
(3)Allow pre-treatment to be targeted drugs, immunosuppressive agents or radiotherapy;
(4)Allow the initial treatment to be chemotherapy combined with targeted drugs.
3.According to the RECISTv 1.1 standard, the subject has at least 1 target lesion that can be evaluated stably;
4.The EpCAM histological staining of the biopsy tumor tissue sample is positive;
5.ECOG physical strength status score 0~1;
6.The subject has sufficient organ and bone marrow function. Laboratory screening must meet the following criteria (refer to NCI CTC AE 5.0). All laboratory test results should be within the following stable range and there is no continuous supportive treatment;
(1)Blood test: white blood cell WBC>=1.5x10^9/L; platelet count PLT >= 60x10^9/L; hemoglobin content Hb>=8.0g/dL; lymphocyte LYM>=0.4x10^9/L;
(2)Blood biochemistry: serum creatinine<=1.5xULN, if serum creatinine > 1.5xULN, creatinine clearance rate must be >50mL/min (calculated according to Cockcroft-Gault formula); serum total bilirubin<=1.5xULN, alanine Aminotransferase (ALT)<=2xULN; Aspartate aminotransferase (AST)<= 2xULN (ALT <= 5xULN in patients with liver metastasis or liver cancer, AST<=5xULN);
(3)Amylase and lipase <= 1.5 x ULN;
(4)Routine urine examination: urine protein < 2+.
7.Left ventricular ejection fraction (LVEF)> 45% in cardiac color Doppler ultrasound examination within one month;
8.Fertility status: female patients of childbearing age or male patients whose sexual partners are females of childbearing age are willing to take effective contraceptive measures from the signing of the informed consent form to 6 months after the last cell infusion; females of childbearing age include premenopausal women and Women within 2 years after menopause. Subjects must agree to follow contraceptive instructions during treatment;
9.The subject must sign and date a written informed consent form;
10.The subject must be willing and able to comply with the predetermined treatment plan, laboratory examination, follow-up and other research requirements.

排除标准：

受试者若符合下列任何一条情况，则不能入选本研究；
1.影妊娠期和哺乳期女性；
2.已知的人类免疫缺陷病毒（HIV）感染史；急性或慢性活动性乙型肝炎（HBsAg阳性）；急性或慢性活动性丙型肝炎（HCV抗体阳性）。梅毒抗体阳性；EB病毒抗体阳性；巨细胞病毒（CMV）感染（IgM阳性）；
3.处于活动期或临床控制不佳的严重感染或在首次单采血后4周内有重度感染；
4.目前存在需要治疗的心脏病或经过研究者判断控制不佳的高血压（定义为经规范化降压药治疗后收缩压>=140 mmHg和/或舒张压>90 mmHg）；
5.存在以下任何心脏临床症状或疾病：
(1)不稳定型心绞痛；
(2)1年内发生过心肌梗死；
(3)静息状态心电图检查QTc>450ms(男性)或者QTc>470ms（女性）；
(4)静息状态心电图检查发现有重要临床意义的异常（如心率、传导、形态特征等异常）或完全性左束支传导阻滞或三级心脏传导阻滞或二级心脏传导阻滞或者PR间期>250ms；
(5)存在增加QTc延长、心率异常风险的因素，如心力衰竭、低钾血症、先天性长QT综合征、长QT综合征家族史或有40岁以下直系亲属不明原因猝死、或有延长间期伴随用药。
6.既往发生过胃肠道穿孔、腹腔脓肿或近期（3个月以内）发生过肠梗阻或影像学、临床症状伴随有肠梗阻者；
7.凝血功能异常（INR>1.5xULN），具有出血倾向或正在接受溶栓或抗凝治疗（如华法林或肝素），患者需要长期抗血小板治疗（阿司匹林 剂量>300mg/day；氯吡格雷 剂量>75mg/day）；
8.在治疗期间内需要使用皮质类固醇或其他免疫抑制药物进行全身治疗的受试者；
9.治疗前血氧饱和度<=95%（接受指氧检测法）；
10.单采前2周内接受过相当于>15mg/天泼尼松的全身性类固醇药物，吸入性类固醇除外；
11.在淋巴细胞清除预处理前，受试者出现了新的心律失常，包括但不限于无法用药物控制的心律失常、需要加压剂的低血压、需要静脉注射抗生素的细菌、真菌或者病毒感染。使用试验抗生素预防感染的受试者由研究者判断是否可以继续参加试验；
12.现患或有中枢神经系统疾病史的患者，如癫痫发作、脑血管缺血/出血、痴呆、小脑疾病或任何伴累及中枢神经系统的自身免疫性疾病；具有临床症状的中枢神经系统转移或脑膜转移，或有其他证据表明患者中枢神经系统转移或脑膜转移灶尚未控制，经研究者判断不适合入组；
13.先前或同时发生其他恶性肿瘤的患者，但以下情况例外：
经过充分治疗的基底细胞或鳞状细胞癌（在入组研究之前需要足够的伤口愈合）；宫颈癌或乳腺癌的原位癌，经过治愈性治疗，在研究前至少 3 年没有复发迹象；原发性恶性肿瘤已经完全切除并完全缓解>=5 年。
14.既往接受过其他的CAR-T治疗、TCR-T治疗；
15.单采前4周内接受过抗PD-1/PD-L1单克隆抗体治疗；
16.既往接受过其他基因治疗的受试者；
17.有严重精神障碍性疾病的受试者；
18.过去1月内曾参加其他的临床研究；
19.受试者因各种原因退出研究，不能再次参加研究。

Exclusion criteria：

Subjects who meet any of the following conditions cannot be selected for this study;
1.Influencing women during pregnancy and lactation;
2.Known history of human immunodeficiency virus (HIV) infection; acute or chronic active hepatitis B (HBsAg positive); acute or chronic active hepatitis C (HCV antibody positive); Syphilis antibody positive; Epstein-Barr virus antibody positive; Cytomegalovirus (CMV) infection (IgM positive);
3.Severe infections in active phase or poor clinical control or severe infections within 4 weeks after the first blood collection;
4.At present, there is a heart disease requiring treatment or a poorly controlled hypertension (defined as systolic blood pressure >=140 mmHg and/or diastolic blood pressure > 90 mmHg after treatment with standardized antihypertensive drugs);
5.The presence of any of the following cardiac clinical symptoms or diseases:
(1)Unstable angina pectoris;
(2)Myocardial infarction occurred within 1 year;
(3)The resting state ECG examination QTc > 450ms (male) or QTc > 470ms (female);
(4)The resting state ECG examination found abnormalities of important clinical significance (such as abnormal heart rate, conduction, morphological characteristics, etc.) or complete left bundle branch block or third-degree heart block or second-degree heart block or PR Interval > 250ms;
(5)There are factors that increase the risk of QTc prolongation and abnormal heart rate, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or sudden death of unexplained reasons in immediate family members under 40, or prolonged periods Period concomitant medication.
6.Subjects have experienced gastrointestinal perforation, abdominal abscess, or recent (within 3 months) intestinal obstruction or imaging, clinical symptoms accompanied by intestinal obstruction;
7.Abnormal coagulation function (INR>1.5xULN), have bleeding tendency or are receiving thrombolysis or anticoagulation therapy (such as warfarin or heparin), patients need long-term antiplatelet therapy (aspirin dose > 300mg/day; clopidogrel) Gray dose> 75mg/day);
8.Subjects who need to use corticosteroids or other immunosuppressive drugs for systemic treatment during the treatment period;
9.The blood oxygen saturation before treatment <= 95% (accept the finger oxygen test method);
10.Received systemic steroids equivalent to >15 mg/day of prednisone within 2 weeks before apheresis, except for inhaled steroids;
11.Before the pretreatment of lymphocyte depletion, the subject has a new arrhythmia, including but not limited to arrhythmia that cannot be controlled with drugs, hypotension that requires pressurizing agents, bacteria, fungi, or viruses that require intravenous antibiotics infection. Subjects who use test antibiotics to prevent infection are up to the investigator to determine whether they can continue to participate in the test;
12.Subjects who are currently suffering from or have a history of central nervous system diseases, such as seizures, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune diseases involving the central nervous system; central nervous system metastases with clinical symptoms Or meningeal metastasis, or there is other evidence that the patient's central nervous system metastasis or meningeal metastasis has not been controlled, and the investigator judged it is not suitable for inclusion;
13.Subjects who have had other malignant tumors before or at the same time, with the following exceptions:
Fully treated basal cell or squamous cell carcinoma (enough wound healing is required before being included in the study); Cervical cancer or breast cancer in situ, after curative treatment, there is no sign of recurrence at least 3 years before the study; The primary malignant tumor has been completely removed and completely remitted for >= 5 years;
14.Have received other CAR-T treatments and TCR-T treatments in the past;
15.Received anti-PD-1/PD-L1 monoclonal antibody treatment within 4 weeks before apheresis;
16.Subjects who have received other gene therapy in the past;
17.Subjects with severe mental disorders;
18 Participated in other clinical studies in the past 1 month;
19.Subjects withdrew from the study due to various reasons and could not participate in the study again.

研究实施时间：

Study execute time：

从 From 2021-07-01 00:00:00至 To 2024-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2021-08-01 00:00:00 至 To 2023-12-01 00:00:00  

干预措施：

Interventions：

组别：

试验组

样本量：

18

Group：

experimental group

Sample size：

干预措施：

自体的CAR-T细胞治疗

干预措施代码：

Intervention：

autologous CAR T cell therapy

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(区县)：

 杨浦区 

Country：

China 

Province：

Shanghai 

City：

Yangpu District 

单位(医院)：

上海长海医院 

单位级别：

三级甲等 

Institution
hospital：

Shanghai Changhai Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

剂量限制性毒性

指标类型：

主要指标

Outcome：

dose-limiting toxicity

Type：

Primary indicator

测量时间点：

单次输注后28天

测量方法：

Measure time point of outcome：

28 days after a single infusion

Measure method：

指标中文名：

客观缓解率

指标类型：

主要指标

Outcome：

objective remission rate

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

无进展生存期

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：

总生存期

指标类型：

主要指标

Outcome：

overall 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：

最大耐受剂量

指标类型：

主要指标

Outcome：

maximum tolerated dose

Type：

Primary indicator

测量时间点：

单次输注后28天

测量方法：

Measure time point of outcome：

28 days after a single infusion

Measure method：

指标中文名：

细胞在体内的拷贝数和持续存活时间

指标类型：

次要指标

Outcome：

the copy number and duration of cell survival in vivo

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

缓解持续时间

指标类型：

主要指标

Outcome：

duration of remission

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

疾病控制率

指标类型：

主要指标

Outcome：

disease control rate

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

药物代谢动力学评价指标

指标类型：

主要指标

Outcome：

pharmacokinetic evaluation index

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

探索性生物标志物评价指标

指标类型：

主要指标

Outcome：

exploratory biomarker evaluation index

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

肿瘤评估

指标类型：

主要指标

Outcome：

tumor assessment

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

 其它  

说明

Fate of sample：

0thers  

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 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）：

开放、单臂研究，不涉及随机方法。

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

Open, single arm, does not involve random methods.

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）：

https://clinicaltrials.gov/。

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

https://clinicaltrials.gov/.

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：

病历记录表和电子采集和管理系统。

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

Case record form and electronic acquisition and management system.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2021-06-08 08:38:44