ChiCTR2600122182 版本V1.1 版本创建时间2026/04/09 17:44:40 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：

 ChiCTR2600122182 

最近更新日期：

Date of Last Refreshed on：

 2026-04-09 17:43:36 

注册时间：

Date of Registration：

 2026-04-09 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

肿瘤靶向性记忆样NK细胞治疗进展期肝癌的安全性及疗效评估的前瞻性、多中心、多队列临床研究方案

Public title：

A prospective, multi-center, multi-cohort clinical study protocol for evaluating the safety and efficacy of tumor-targeting memory-like NK cells in the treatment of advanced hepatocellular carcinoma.

注册题目简写：

English Acronym：

研究课题的正式科学名称：

肿瘤靶向性记忆样NK细胞治疗进展期肝癌的安全性及疗效评估的前瞻性、多中心、多队列临床研究方案

Scientific title：

A prospective, multi-center, multi-cohort clinical study protocol for evaluating the safety and efficacy of tumor-targeting memory-like NK cells in the treatment of advanced hepatocellular 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：

沈洁 

研究负责人：

刘宝瑞/沈洁 

Applicant：

Jie Shen 

Study leader：

Baorui Liu/Jie Shen 

申请注册联系人电话：

Applicant telephone：

 +86 25 8310 6666

研究负责人电话：

Study leader's
telephone：

+86 25 8310 6666

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：

 shenjie2008nju@163.com

研究负责人电子邮件：

Study leader's E-mail：

 shenjie2008nju@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：

江苏省南京市中山路321号

研究负责人通讯地址：

江苏省南京市中山路321号

Applicant address：

321 Zhongshan Road, Nanjing, Jiangsu

Study leader's address：

321 Zhongshan Road, Nanjing, Jiangsu

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：

南京大学医学院附属鼓楼医院

Applicant's institution：

Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School

研究负责人所在单位：

南京大学医学院附属鼓楼医院

Affiliation of the Leader：

Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School

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：

 SC2026-0002-02

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：

南京大学医学院附属鼓楼医院干（体）细胞临床研究伦理委员会

Name of the ethic committee：

The Clinical Research Ethics Committee for Stem Cells of the Affiliated Drum Tower Hospital of Nanjing University Medical School

伦理委员会批准日期：

Date of approved by ethic committee：

 2026-03-18 00:00:00

伦理委员会联系人：

戴建

Contact Name of the ethic committee：

Jian Dai

伦理委员会联系地址：

江苏省南京市中山路321号

Contact Address of the ethic committee：

321 Zhongshan Road, Nanjing, Jiangsu

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 25 8310 6666

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：

南京大学医学院附属鼓楼医院

Primary sponsor：

Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School

研究实施负责（组长）单位地址：

江苏省南京市中山路321号

Primary sponsor's address：

321 Zhongshan Road, Nanjing, Jiangsu

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

江苏

市(区县)：

Country：

China

Province：

Jiangsu

City：

单位(医院)：

南京大学医学院附属鼓楼医院

具体地址：

江苏省南京市中山路321号

Institution
hospital：

Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School

Address：

321 Zhongshan Road, Nanjing, Jiangsu

经费或物资来源：

自筹及金陵药业

Source(s) of funding：

Self-financed and Jinling Pharmaceutical Company

研究疾病：

肝癌  

Target disease：

Hepatocellular Carcinoma

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：

 其它 

Study phase：

N/A

研究设计：

非随机对照试验 

Study design：

Non randomized control 

研究目的：

本研究是一项前瞻性多中心多队列研究，主要是探索记忆样NK细胞联合一线靶向免疫治疗进展期肝细胞癌的安全性与疗效及逆转耐药的价值。  

Objectives of Study：

This study is a prospective, multicenter, multi-cohort research, mainly aimed at exploring the safety and efficacy of memory-like NK cells combined with first-line targeted immunotherapy in advanced hepatocellular carcinoma, as well as the value of reversing drug resistance.

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. 受试者能够理解知情同意书，自愿参与并签署知情同意书。 2. 年龄≥18 岁，ECOG 评分0-1分。 3. 经指南推荐的一线标准治疗失败（治疗后疾病进展或治疗毒副作用 不可耐受）的肝内多发和/或远处转移的肝细胞癌患者；或者未经任 何治疗的，经组织学或细胞学和/或影响评估为肝细胞癌肺转移患 者，至少有一个可测量病灶用于疗效评价。 4. 所有受试者尽可能提供在签署知情前2年内存档或新鲜获取的肿瘤 组织样本，优选新近获得肿瘤组织样本。 5. 血液、肝脏和肾脏功能符合以下标准： a) 中性粒细胞计数≥1.5 × 10^9/L b) 血小板计数≥75 × 10^9/L； c) 血红蛋白浓度≥90 g/L； d) 血清白蛋白浓度≥30 g/L； e) 胆红素≤50 μmol/L； f) AST和ALT < 5×ULN，ALP < 4×ULN； g) INR≤2.3； h) 肌酐 < 1.5×ULN。 6. 肝功能Child-Pugh A级 7. 育龄期受试者在入组前和试验中需采取恰当的保护措施（避孕措施 或其他控制生育的方法）。 8. 预计生存时间≥3 个月。 9. 患者自愿加入本研究，签署知情同意书，依从性好。

Inclusion criteria

1. The subjects were able to understand the informed consent form, voluntarily participated and signed the informed consent form. 2. Age >= 18 years old, ECOG score 0-1. 3. Patients with multiple and/or distant liver metastases of hepatocellular carcinoma who failed the first-line standard treatment (disease progression after treatment or intolerable treatment side effects) as recommended by the guidelines; or patients without any treatment, diagnosed as hepatocellular carcinoma lung metastasis by histological or cytological and/or impact assessment, with at least one measurable lesion for efficacy evaluation. 4. All subjects should provide tumor tissue samples that are archived or freshly obtained within 2 years before signing the informed consent form, preferably the newly obtained tumor tissue samples. 5. Blood, liver and kidney functions meet the following standards: (1) Neutrophil count >= 1.5 × 10^9/L (2) Platelet count >= 75 × 10^9/L; (3) Hemoglobin concentration >= 90 g/L; (4) Serum albumin concentration >= 30 g/L; (5) Bilirubin <= 50 μmol/L; (6) AST and ALT < 5×ULN, ALP < 4×ULN; (7) INR <= 2.3; (8) Creatinine < 1.5×ULN. 6. Liver function is Child-Pugh grade A. 7. Pregnant or breastfeeding subjects need to take appropriate protective measures (contraceptive measures or other methods to control fertility) before enrollment and during the trial. 8. Expected survival time >= 3 months. 9. Patients voluntarily joined this study, signed the informed consent form, and had good compliance.

排除标准：

1. 首次给药前2 周内针对病灶进行姑息性局部治疗；首次给药前 2 周内接受过系统性非特异性免疫调节治疗（如白介素、干扰素、胸腺肽等）；首次给药前 2 周内曾接受具有抗肿瘤适应症的中草药或中成药。 2. 受试者有活动性细菌或真菌感染（>= 2 级 of NCI-CTC, 第3版）。 3. 受试者有HIV，HCV，HBV感染，不可控制的冠状动脉疾病或哮喘， 不可控制的脑血管疾病或研究者认为的不可入组的其它疾病。 4. 受试者有自身免疫性疾病或免疫缺陷，应用免疫抑制药物治疗者。 5. 妊娠、哺乳期妇女。育龄期妇女入组前 7 天内必须测试妊娠试验阴性。 6. 滥用药物，临床或心理的或社会的因素使知情同意或研究实施受影响。 7. 治疗前28天内接种过活疫苗接种。 8. 需要长期系统性激素或任何其它免疫抑制药物治疗的受试者，不包括吸入激素治疗。 9. 在首剂研究治疗之前4周之内接受过重大的外科手术（开颅、开胸或开腹手术）或者预期在研究治疗期间需要接受大手术。 10. 有症状且需要临床干预的中枢神经系统转移的受试者。 11. 可能对研究药物或其任何辅料过敏者。 12. 在入组前2周内出现消化道出血或出血风险高的受试者。 13. 研究者认为不适合纳入者。

Exclusion criteria：

1. Within 2 weeks prior to the first administration, perform palliative local treatment for the lesion; within 2 weeks prior to the first administration, have received systemic non-specific immunomodulatory therapy (such as interleukins, interferons, thymosin, etc.); within 2 weeks prior to the first administration, have received traditional Chinese medicine or Chinese patent medicine with anti-tumor indications. 2. The subject has active bacterial or fungal infection (>= 2 grade of NCI-CTC, version 3). 3. The subject has HIV, HCV, HBV infection, uncontrolled coronary artery disease or asthma, uncontrolled cerebrovascular disease or other diseases that the investigator considers not eligible for inclusion. 4. The subject has autoimmune diseases or immunodeficiency, and is being treated with immunosuppressive drugs. 5. Pregnant or lactating women. Women of childbearing age must test negative for pregnancy within 7 days before enrollment. 6. Abusing drugs, with clinical or psychological or social factors affecting informed consent or study implementation. 7. Within 28 days before treatment, received live vaccine vaccination. 8. Subjects requiring long-term systemic hormone or any other immunosuppressive drug treatment, excluding inhaled hormone treatment. 9. Within 4 weeks before the first study treatment, received major surgical procedures (craniotomy, thoracotomy or laparotomy) or expected to need major surgery during the study treatment. 10. Subjects with symptomatic and requiring clinical intervention central nervous system metastasis. 11. Those who may be allergic to the study drug or any of its excipients. 12. Subjects with gastrointestinal bleeding or high risk of bleeding within 2 weeks before enrollment. 13. Subjects considered not eligible for inclusion by the investigator.

研究实施时间：

Study execute time：

从 From 2026-03-10 00:00:00至 To 2029-03-10 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2026-04-10 00:00:00 至 To 2029-03-10 00:00:00

干预措施：

Interventions：

组别：

队列1

样本量：

 10

Group：

Cohort 1

Sample size：

干预措施：

病理及影像评估为肝细胞癌患者，一线标准治疗进展：受试者在治疗第 1 天、第 3 天接受病灶部位的放疗：2Gy×2f；每天继续接受靶向治疗（药物与一线治疗一致）；第 5 天接受免疫治疗（药物与一线治疗一致）和记忆样 NK 细胞静脉回输，第 12 天再次接受记忆样 NK 细静脉回输，21 天为一个治疗周期，两周期细胞回输后进行疗效评价，后续继续靶向联合免疫治疗维持治疗，并进入随访期。

干预措施代码：

Intervention：

The pathological and imaging assessment indicated that the patient was diagnosed with hepatocellular carcinoma. The first-line standard treatment failed: The subject received radiotherapy at the lesion site on the 1st and 3rd days of treatment: 2Gy × 2f; continued to receive targeted therapy (the same drugs as the first-line treatment) every day; received immunotherapy on the 5th day (the same drugs as the first-line treatment) and intravenous infusion of memory-like NK cells; received intravenous infusion of memory-like NK cells again on the 12th day; 21 days constituted one treatment cycle. After two cycles of cell infusion, the efficacy was evaluated, and then continued targeted combined immunotherapy for maintenance treatment, and entered the follow-up period.

Intervention code：

组别：

队列2

样本量：

 10

Group：

Cohort 2

Sample size：

干预措施：

病理及影像评估为肝细胞癌肺转移患者，未经任何治疗：受试者在治疗第 1 天、第 3 天接受病灶部位的放疗：2Gy×2f；每天继续接受靶向治疗（药物与标准一线治疗一致）；第 5 天接受免疫治疗（药物与标准一线治疗一致）及记忆样 NK 细胞静脉注回输，第 12 天再次接受记忆样 NK 细胞静脉回输，21 天为一个治疗周期，两周期细胞回输后进行疗效评价，后续继续靶向联合免疫治疗维持治疗，并进入随访期。

干预措施代码：

Intervention：

The patient was diagnosed with liver cell carcinoma with lung metastasis and had not received any treatment: On the 1st and 3rd days of the treatment, radiotherapy was administered to the lesion site: 2Gy × 2f; The targeted therapy (the same as the standard first-line treatment) was continued every day; On the 5th day, immunotherapy (the same as the standard first-line treatment) and intravenous infusion of memory-like NK cells were received; On the 12th day, memory-like NK cells were again intravenously infused; 21 days constituted one treatment cycle. After two cycles of cell infusion, the efficacy was evaluated, and then targeted combined immunotherapy was continued for maintenance treatment, and the follow-up period was initiated.

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 江苏 

市(区县)：

  

Country：

China

Province：

Jiangsu

City：

单位(医院)：

 南京鼓楼医院集团宿迁医院 

单位级别：

 三甲 

Institution
hospital：

Nanjing Drum Tower Hospital Group Suqian Hospital

Level of the institution：

Tertiary

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 (DLT)

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

不良事件的发生率

指标类型：

主要指标

Outcome：

The incidence rate of adverse events

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

体格检查

指标类型：

主要指标

Outcome：

physical examination

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

生命体征

指标类型：

主要指标

Outcome：

vital signs

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：

次要指标

Outcome：

progression free 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：

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：

疾病控制率

指标类型：

次要指标

Outcome：

Disease control rate

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：

肿瘤组织

组织：

Sample Name：

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 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

是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）：

临床试验公共管理平台 http://www.medresman.org.cn

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

Clinical Trial Management Public Platform http://www.medresman.org.cn

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：

暂未确定/Not yet

注册人：

Name of Registration：

  2026-04-09 17:43:30