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：	ChiCTR2200060032
最近更新日期： Date of Last Refreshed on：	2023-03-05 14:52:57
注册时间： Date of Registration：	2022-05-15 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	请与我们联系完善试验主办单位、研究实施单位、测量指标信息。 MSLN STAR-T细胞在晚期恶性实体瘤中的安全性与有效性的探索性临床研究
Public title：	An exploratory clinical study on the safety and efficacy of MSLN STAR-T cells in advanced malignant solid tumors
注册题目简写：
English Acronym：
研究课题的正式科学名称：	MSLN STAR-T细胞在晚期恶性实体瘤中的安全性与有效性的探索性临床研究
Scientific title：	An exploratory clinical study on the safety and efficacy of MSLN STAR-T cells in advanced malignant solid tumors
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：	李珏为	研究负责人：	沈琳
Applicant：	Li Juewei	Study leader：	Shen Lin
申请注册联系人电话： Applicant telephone：	+86 18510842504	研究负责人电话： Study leader's telephone：	+86 13911219511
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：	lijuewei@cn-immunotech.cn	研究负责人电子邮件： Study leader's E-mail：	doctorshenlin@sina.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：	北京市昌平区医科路9号院1号楼地上第五层（昌平示范园）	研究负责人通讯地址：	北京市海淀区阜成路52号
Applicant address：	9 Yike Road, Changping District, Beijing	Study leader's address：	52 Fucheng Road, Haidian District, Beijing
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：	华夏英泰（北京）医药科技有限公司
Applicant's institution：	Huaxia Yingtai (Beijing) Pharmaceutical Technology Co., Ltd.
研究负责人所在单位：
Affiliation of the Leader：

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：	2022YJZ09	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：	北京肿瘤医院医学伦理委员会
Name of the ethic committee：	Medical Ethics Committee of Beijing Cancer Hospital
伦理委员会批准日期： Date of approved by ethic committee：	2022-03-01 00:00:00
伦理委员会联系人：	廖老师
Contact Name of the ethic committee：	Teacher Liao
伦理委员会联系地址：	北京市海淀区阜成路81号
Contact Address of the ethic committee：	81 Fucheng Road, Haidian District, Beijing
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：

北京肿瘤医院

Primary sponsor：

Beijing Cancer Hospital

研究实施负责（组长）单位地址：

北京市海淀区阜成路52号

Primary sponsor's address：

52 Fucheng Road, Haidian District, Beijing

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	北京	市(区县)：
Country：	China	Province：	Beijing	City：
单位(医院)：	北京肿瘤医院	具体地址：	海淀区阜成路52号
Institution hospital：	Beijing Cancer Hospital	Address：	52 Fucheng Road, Haidian District

经费或物资来源：

资助方

Source(s) of funding：

sponsor

研究疾病：

MSLN阳性的晚期恶性实体肿瘤

Target disease：

MSLN-positive advanced malignant solid tumor

研究疾病代码：

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

I期临床试验

Study phase：

1

研究设计：

横断面

Study design：

Cross-sectional

研究目的：

评价MSLN STAR-T细胞在晚期恶性实体瘤受试者中的安全性和耐受性。

Objectives of Study：

To evaluate the safety and tolerability of MSLN STAR-T cells in subjects with advanced malignant solid tumors.

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岁，≤70岁，性别不限；
2.经组织学或细胞学确诊的晚期恶性实体瘤，包括恶性间皮瘤（胸膜、腹膜等）、胰腺癌、卵巢癌、肝内胆管癌、肺癌、胃癌、结直肠癌等；
3.经过系统性治疗后复发，或无法耐受现有治疗的晚期恶性实体瘤患者，包括但不限于：
（1）既往接受过至少一线治疗失败的恶性间皮瘤患者；
（2）既往接受至少一线治疗失败的胰腺癌患者；
（3）既往接受至少二线治疗失败的胃癌患者；
（4）既往接受过至少二线铂敏感或铂耐药治疗失败的卵巢癌患者；
（5）既往接受过至少一线治疗失败的肝内胆管癌患者；
（6）晚期非小细胞肺癌（非鳞癌）患者：EGFR、ALK、ROS1、MET等驱动基因阳性者，经靶向治疗后出现疾病进展或不能耐受；EGFR、ALK、ROS1、MET等驱动基因阴性者，受试者既往接受≥1线治疗后出现疾病进展或不能耐受；
（7）既往接受过至少二线治疗失败的结直肠癌患者；
4.肿瘤组织样本间皮素（MSLN）为阳性（IHC检测，阳性率>10%）；
5.筛选时影像学上具有可测量的靶病灶（依据RECIST1.1），非淋巴结病灶长径≥1.0cm，或淋巴结病灶短径≥1.5cm；
6.ECOG评分0-1分；
7.预期生存期≥3个月；
8.具备建立外周血单个核细胞采集通路的条件，具有足够的细胞以备STAR-T细胞制备；
9.具有良好的骨髓和器官功能：
（1）血常规：绝对中性粒细胞计数（ANC）≥1.5×10^9/L；血红蛋白（Hb）≥85g/L；血小板计数≥75×10^9/L；
（2）血生化：总胆红素（TBIL）≤2.5倍正常值上限（ULN）；天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）≤2.5倍正常值上限（ULN）（肝转移的患者可为≤5倍ULN）；
（3）血清肌酐（Cr）≤1.5倍正常值上限（ULN）；
（4）凝血功能：国际标准化比值（INR）、活化部分凝血酶原时间（APTT）≤1.5×ULN，肝转移的患者应≤2×ULN；
（5）肺功能：具备最低水平的肺储备，定义为CTCAE v5.0≤1级呼吸困难且在非吸氧状态的指末血氧饱和度≥ 91%；
10. 育龄期妇女必须在筛选期进行血清学妊娠试验，且结果为阴性；并且愿意在试验期间和细胞输注后24个月采用可靠的方法避孕；对于伴侣为育龄妇女的男性受试者，应接受手术绝育，或同意在试验期间和细胞回输后24个月采用可靠的方法避孕；
11. 受试者自愿加入本研究，签署知情同意书，依从性好，配合随访。

Inclusion criteria

1. Aged 18-70 years, no gender limit;
2. Advanced malignant solid tumors confirmed by histology or cytology, including malignant mesothelioma (pleura, peritoneum, etc.), pancreatic cancer, ovarian cancer, intrahepatic bile duct cancer, lung cancer, gastric cancer, colorectal cancer, etc.;
3. Patients with advanced malignant solid tumor who relapse after systematic treatment or cannot tolerate existing treatment, including but not limited to:
(1) Patients with malignant mesothelioma who have previously received at least first-line treatment failure;
(2) Patients with pancreatic cancer who had previously failed at least first-line therapy;
(3) Gastric cancer patients who had failed at least second-line treatment;
(4) Ovarian cancer patients who had received at least second-line platinum-sensitive or platinum-resistant treatment in the past;
(5) Patients with intrahepatic cholangiocarcinoma who had received at least first-line treatment failure;
(6) Patients with advanced non-small cell lung cancer (non-squamous cell carcinoma) : patients with EGFR, ALK, ROS1, MET and other driver genes positive who developed disease progression or intolerance after targeted therapy; Patients with negative EGFR, ALK, ROS1, MET and other driver genes developed disease progression or intolerance after receiving >=1 line therapy;
(7) Patients with colorectal cancer who had failed at least second-line treatment in the past;
4. Mesenchymal (MSLN) was positive in tumor tissue samples (>10% by IHC detection);
5. During screening, there were measurable target lesions on imaging (according to RECIST1.1), with the length diameter of non-lymph node lesions >=1.0cm or the short diameter of lymph node lesions >=1.5cm;
6. ECOG score 0-1;
7. Expected survival >=3 months;
8. Having the conditions to establish the peripheral blood mononuclear cell collection pathway and having enough cells to prepare STAR-T cells;
9. Good bone marrow and organ function:
(1) Blood routine: absolute neutrophil count (ANC) >=1.5x10^9/L; Hemoglobin (Hb) >=85g/L; Platelet count >=75x10^9/L;
(2) Blood biochemistry: total bilirubin (TBIL) <=2.5 times the upper limit of normal value (ULN); Aspartate aminotransferase (AST), alanine aminotransferase (ALT) <=2.5 times the upper limit of normal (ULN) (patients with liver metastasis may be <=5 times ULN);
(3) Serum creatinine (Cr) <=1.5 times the upper limit of normal (ULN);
(4) Coagulation function: International normalized ratio (INR), activated partial prothrombin time (APTT) <=1.5xULN, patients with liver metastasis <=2xULN;
(5) Lung function: having the lowest level of lung reserve, defined as CTCAE v5.0<= grade 1 dyspnea and end-finger oxygen saturation >= 91% in non-oxygenated state;
10. Patients of childbearing age must undergo serological pregnancy tests during the screening period and the results are negative; And willing to use a reliable method of contraception during the trial and 24 months after the cell infusion; Male patients whose partners are women of reproductive age should be surgically sterilized or agree to use a reliable method of contraception during the trial period and for 24 months after cell transfusion;
11. The patients voluntarily joined the study, signed the informed consent, had good compliance, and cooperated with follow-up.

排除标准：

1.筛选时存在难以控制的活动性感染者；符合以下一项者：
乙肝表面抗原（HBsAg）阳性和/或乙肝e抗原（HBeAg）阳性，乙肝e抗体（HBe-Ab）和/或乙肝核心抗体（HBc-Ab）阳性且HBV-DNA拷贝数大于检测下限，丙肝抗体（HCV-Ab）阳性且HCV-RNA拷贝数大于检测下限，人体免疫缺陷病毒（HIV）抗体阳性者、梅毒螺旋体（TP-Ab）抗体阳性；
2.患有或具有中枢神经系统疾病史的患者，如癫痫史、中风、严重脑损伤失语、瘫痪等；
3.存在活动性脑转移的患者，但筛选前1个月不需要采用任何放射、手术或类固醇治疗以控制转移症状者可入组；
4.系统性红斑狼疮、合并活动性或未经控制自身免疫性疾病（如Crohns病、类风湿关节炎、自身免疫性溶血性贫血等）；
5.正在接受治疗剂量或系统性的糖皮质激素治疗（泼尼松≥20mg/天或等效剂量的其他皮质类固醇激素）；
6.既往干预或治疗导致的毒性或并发症未恢复至CTCAE v5.0≤2级或以下（脱发及研究者判断的无临床意义的实验室检查异常值除外）；
7.既往接受过其他基因修饰的T细胞产品（如MSLN CAR-T 或TCR-T细胞），或靶向MSLN的治疗；
8.单采前的指定时间内使用进行过以下任何药物或治疗的患者：
（1）在单采前2周内或5个半衰期内（以时间短者为准）接受过任何化疗；
（2）在单采前4周内或5个半衰期内（以时间短者为准）接受过任何单克隆抗体、抗体偶联药物（ADC）、双抗等大分子或小分子靶向治疗；
（3）在单采前6周内接受过放疗，若放疗部位疾病进展，或其它未放疗部位存在CT等影像阳性病灶，则允许入组；若其它未放疗部位存在CT等影像阳性病灶，允许在单采前2周，对单一病灶进行放疗；
9.存在无法控制的胸水、心包积液或腹水（腹水定义为：体格检查腹水体征阳性或需要采用干预治疗控制的腹水（仅影像学显示有腹水而不需干预者可纳入）；
10.筛选前的3年内，被诊断出其他恶性肿瘤，但经过治疗的皮肤基底细胞癌，皮肤鳞状细胞癌和/或经过根治性原位癌切除者除外；
11.其他严重的可能限制受试者参加此研究的疾病。例如控制不良的糖尿病、左心室射血分数（LVEF）<50%、纽约心脏病协会（NYHA）心功能III级或IV级心力衰竭；6个月内心肌梗死、不稳定型心律失常或不稳定性心绞痛；1年内的肺栓塞病史；中度及以上的慢性阻塞性肺疾病、间质性肺病（影像学上无临床意义的间质性改变除外）、有临床意义的肺功能检查异常；或有临床意义的消化道出血；
12.筛选前6周接种过活疫苗者；
13.在细胞回输前3个月内参与其他干预性临床研究，接受过活性试验药物治疗，或在整个研究期间有意参与另一项临床试验或接受方案规定之外的抗肿瘤治疗者。
14.妊娠或哺乳期妇女；
15.研究者认为存在不适合入选或影响受试者参与或完成研究的其他因素。

Exclusion criteria：

1. There are active infected persons who are difficult to control during screening; Meet one of the following criteria:
Hepatitis B surface antigen (HBsAg) positive and/or Hepatitis Be antigen (HBeAg) positive, Hepatitis Be antibody (HBe-Ab) and/or Hepatitis B core antibody (HCB-AB) positive and HBV-DNA copy number greater than the lower limit, hepatitis C antibody (HCV-Ab) positive and HCV-RNA copy number greater than the lower limit, human immunodeficiency virus (HIV) antibody positive, treponema pallidum (TP-Ab) antibody positive;
2. Patients with or with a history of central nervous system diseases, such as epilepsy, stroke, severe brain injury, aphasia, paralysis, etc.;
3. Patients with active BMS who did not require any radiation, surgery, or steroid therapy to control metastatic symptoms 1 month before screening were enrolled;
4. Systemic lupus erythematosus, combined with active or uncontrolled autoimmune diseases (such as Crohns disease, rheumatoid arthritis, autoimmune hemolytic anemia, etc.);
5. Currently receiving therapeutic dose or systemic corticosteroid therapy (prednisone >=20mg/ day or equivalent dose of other corticosteroids);
6. Toxicity or complications caused by previous intervention or treatment do not return to CTCAE v5.0<=2 or below (except for hair loss and laboratory test outliers judged by the investigator as not clinically significant);
7. Previously received other genetically modified T cell products (such as MSLN CAR T or TCR-T cells), or targeted MSLN therapy;
8. Patients who have received any of the following medications or treatments during a specified time before apheresis:
(1) Received any chemotherapy within 2 weeks prior to anemiculture or within 5 half-lives, whichever is shorter;
(2) Received any large or small molecule targeted therapy, such as monoclonal antibody, antibody-coupled drug (ADC), or double antibody, within 4 weeks or 5 half-lives, whichever is shorter;
(3) Patients who had received radiotherapy within 6 weeks prior to anapheresis were allowed to be included if the disease progressed at the radiotherapy site or if there were positive lesions such as CT images at other sites without radiotherapy; If there were positive lesions on CT and other images in other sites without radiotherapy, radiotherapy was allowed for a single lesion 2 weeks before monocele;
9. There is uncontrolled pleural effusion, pericardial effusion or ascites (ascites defined as: ascites with positive signs of ascites on physical examination or ascites requiring intervention (only those with ascites shown on imaging without intervention can be included);
10. Other malignancies were diagnosed within 3 years prior to screening, except for treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or radical resection of carcinoma in situ;
11. Other serious medical conditions that may limit participants' participation in the study. Examples include poorly controlled diabetes, left ventricular ejection fraction (LVEF) <50%, New York Heart Association (NYHA) heart function Class III or IV heart failure; Myocardial infarction, unstable arrhythmia, or unstable angina within 6 months; History of pulmonary embolism within 1 year; Moderate or above chronic obstructive pulmonary disease, interstitial lung disease (except radiologically insignificant interstitial changes), and clinically significant abnormalities in lung function; Or gastrointestinal bleeding of clinical significance;
12. Patients who received live vaccine 6 weeks prior to screening;
13. Those who participated in other interventional clinical studies in the 3 months prior to cell retransfusion, received active investigational drug therapy, or intended to participate in another clinical trial or receive antitumor therapy outside protocol requirements during the study period;
14. Pregnant or lactating patients;
15. The investigator considers that there are other factors unsuitable for inclusion or affecting the patient's participation in or completion of the study.

研究实施时间：

Study execute time：

从 From 2022-04-14 00:00:00至 To 2025-04-01 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2022-05-05 00:00:00 至 To 2025-02-01 00:00:00

干预措施：

Interventions：

组别：	干预组	样本量：	15
Group：	Intervention group	Sample size：	15
干预措施：	MSLN STAR-T 细胞输注	干预措施代码：
Intervention：	MSLN STAR-T cell infusion	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	北京	市(区县)：
Country：	China	Province：	Beijing	City：
单位(医院)：	北京肿瘤医院	单位级别：	三甲
Institution hospital：	Beijing Cancer 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：		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：		测量方法：
Measure time point of outcome：		Measure method：

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：		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：

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）：

开放性试验

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

open trial

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

不公开/Private

盲法：
Blinding：

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）：	NA
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	NA
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：	Na
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	NA
数据与安全监察委员会： Data and Safety Monitoring Committee：	有/Yes
注册人： Name of Registration：	2022-05-15 23:46:32