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：	ChiCTR2200059508
最近更新日期： Date of Last Refreshed on：	2023-02-09 21:58:52
注册时间： Date of Registration：	2022-05-03 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	HS-IT101自体肿瘤浸润淋巴细胞（TIL）注射液治疗晚期乳腺癌的安全性和有效性的临床研究
Public title：	Study on the safety and efficacy of autogenous tumor infiltrates the lymphocytes (HS-IT101) in the treatment of patients with advanced breast cancer
注册题目简写：
English Acronym：
研究课题的正式科学名称：	HS-IT101自体肿瘤浸润淋巴细胞（TIL）注射液治疗晚期乳腺癌的安全性和有效性的临床研究
Scientific title：	Study on the safety and efficacy of autogenous tumor infiltrates the lymphocytes (HS-IT101) in the treatment of patients with advanced breast 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：	刘文娜	研究负责人：	王海波、曹玉
Applicant：	Liu Wenna	Study leader：	Wang Haibo, Cao Yu
申请注册联系人电话： Applicant telephone：	+86 15065429261	研究负责人电话： Study leader's telephone：	+86 18661805787
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：	liuwenna@sino-cellbiomed.com	研究负责人电子邮件： Study leader's E-mail：	hbwang66@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：	山东省青岛市即墨区鳌山卫蓝谷观山路276号海科创业中心8号楼	研究负责人通讯地址：	山东省青岛市江苏路16号
Applicant address：	276 Guanshan Road, Lan'gu, Aoshanwei Street, Jimo District, Qingdao, Shandong	Study leader's address：	16 Jiangsu Road, Qingdao, Shandong
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：	青岛华赛伯曼医学细胞生物有限公司
Applicant's institution：	Qingdao Sino-Cell Biomedicine 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：	细临伦审QYFYEC 2022-001-01	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：	青岛大学附属医院伦理委员会
Name of the ethic committee：	The Affiliated Hospital of Qingdao University Ethics Committee
伦理委员会批准日期： Date of approved by ethic committee：	2022-06-29 00:00:00
伦理委员会联系人：	韩燕
Contact Name of the ethic committee：	Han Yan
伦理委员会联系地址：	山东省青岛市江苏路16号青岛大学附属医院重症医学科
Contact Address of the ethic committee：	16 Jiangsu Road, Qingdao, Shandong
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：

青岛大学附属医院

Primary sponsor：

The Affiliated Hospital of Qingdao University

研究实施负责（组长）单位地址：

山东省青岛市江苏路16号

Primary sponsor's address：

16 Jiangsu Road, Qingdao, Shandong

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	山东	市(区县)：	青岛
Country：	China	Province：	Shandong	City：	Qingdao
单位(医院)：	青岛大学附属医院	具体地址：	江苏路16号
Institution hospital：	The Affiliated Hospital of Qingdao University	Address：	16 Jiangsu Road

经费或物资来源：

青岛华赛伯曼医学细胞生物有限公司

Source(s) of funding：

Qingdao Sino-Cell Biomedicine Co., Ltd.

研究疾病：

晚期乳腺癌

Target disease：

Advanced Breast Cancer

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：

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：

1.主要目的：评估HS-IT101 TIL细胞注射液在晚期乳腺癌患者中的安全性和耐受性。 2.次要目的：评估HS-IT101 TIL细胞注射液治疗晚期乳腺癌的初步有效性。 3.探索性目的：（1）探索HS-IT101 TIL细胞注射液的药代动力学（PK）特征；（2）探索HS-IT101 TIL细胞注射液的药效动力学（PD）特征。

Objectives of Study：

1. Main objective: To evaluate the safety and tolerability of HS-IT101 TIL cell injection in patients with advanced breast cancer. 2. Secondary objective: To evaluate the initial efficacy of HS-IT101 TIL cell injection in the treatment of advanced breast cancer. 3. Exploratory objective: (1) To explore the pharmacokinetic (PK) characteristics of HS-IT101 TIL cell injection; (2) To explore the pharmacodynamic (PD) characteristics of HS-IT101 TIL cell injection.

药物成份或治疗方案详述：

Description for medicine or protocol of treatment in detail：

纳入标准：

Inclusion criteria

1. Aged 18-75 years (including the critical value);
2. Clinically diagnosed patients with advanced advanced breast cancer (female);
3. Progression of disease after at least one standard treatment; There is no effective treatment available or other treatments are refused (refer to the latest version of Diagnosis and treatment guidelines for each cancer for ''effective treatment'');
4. There is at least one resectable tumor lesion that has not received radiotherapy or other local therapy within 28 days, from which at least a 1cm^3 volume of tissue can be isolated, or a sufficient TIL can be prepared (either from a single lesion or from a combination of multiple lesions); If no lesions can be resected, a tumor sample of similar size should be obtained by puncture or bronchoscopy for the preparation of autologous tumor infiltrating lymphocytes (minimally invasive treatment as possible);
5. At least one measurable lesion, as defined by RECIST 1.1, that has not received radiotherapy or other local therapy (unless such therapy occurred earlier than 28 days and the lesion has shown substantial progression);
6. ECOG <=2;
7. Expected survival time >=3 months;
8. There was adequate organ and bone marrow function at the assessment within the 7-day (+ 3-day window) initial screening, as defined below:
(1) Blood routine: neutrophil count >=1.5x10^9/L, platelet count >=90x10^9/L, hemoglobin >=90g/L (no blood transfusion or erythropoietin treatment within 14 days);
(2) Liver function: ALT and AST levels <=2.5xULN, ALT and AST levels <=5xULN in patients with liver metastasis; Serum total bilirubin <=1.5xULN;
(3) Renal function: serum creatinine <=1.5xULN or CCr>=45mL/min (Cockcroft-Gault formula);
(4) Coagulation function: activated partial thromboplastin time (APTT) <=1.5xULN, International Normalized ratio (INR) or prothrombin time (PT) <=1.5xULN;
(5) Cardiopulmonary function: left ventricular ejection fraction (LVEF)>50% by color ultrasound; Asymptomatic or poorly controlled arrhythmia; QT interval was not prolonged, QTc<=470ms; Pulmonary function tests with FEV1>60% or FEV1/FVC>0.7, and percutaneous oxygen saturation >=92% at rest;
9. Prior to tumor sampling, adverse reactions caused by previous treatment had recovered to CTCAE 5.0 <=1 (except for toxicity without safety risk as determined by researchers, such as hair loss);
10. Patients who have agreed to take effective non-drug contraception within 180 days from signing the informed consent to the end of the study;
11. Those who fully understand the test and voluntarily sign the informed consent.

排除标准：

1.已知对试验用相关药物（环磷酰胺、氟达拉滨、白介素-2）及其活性成分和（或）任何辅料有过重度过敏反应（≥3级）；
2.具有任何无法控制的临床问题，包括但不限于：
（1）药物控制不良的高血压（服药后安静状态下血压≥150/90mmHg）；
（2）控制不佳的糖尿病；
（3）心脏疾病（纽约心脏病协会定义的III/IV级充血性心力衰竭或心脏传导阻滞）；
3.筛选前6个月内出现过如下情况：深静脉血栓或肺栓塞；心肌梗死；严重或不稳定性心律失常或心绞痛；经皮冠状动脉介入治疗、急性冠脉综合征、冠状动脉旁路移植术；脑血管意外、短暂性脑缺血发作、脑栓塞；
4.活动性的、研究期间需要全身性治疗的自身免疫性疾病或接受器官移植者，或既往2年内的该类疾病病史；
5.在入组前14天内使用过任何免疫抑制药物，如皮质类固醇等。允许使用生理剂量的糖皮质激素（≤10 mg/天的泼尼松或等效药物）；允许吸入、鼻内或局部使用皮质类固醇；
6.有症状的脑转移。对于无症状脑转移或经过脑转移病灶治疗后症状稳定的患者，符合下列所有标准可参与本项研究：
（1）中枢神经系统之外有可测量的病灶，允许通过放射或手术治疗脑转移瘤；
（2）病灶最大直径≤ 1cm和病灶数量≤ 3例；
（3）无脑膜、中脑、脑桥、延髓或脊髓转移；
（4）入组前保持临床稳定状态至少4周；
7. TIL采集前使用的抗癌治疗：过去4周内化疗、免疫检查点抑制剂、其他试验药物治疗或针对靶病灶的局部治疗；过去2周内接受过具有抗肿瘤适应症的中成药或免疫调节作用的药物（包括胸腺肽、干扰素）系统性全身治疗；过去4周内接受过靶向药物（若靶向药物代谢5个半衰期小于4周，以5个半衰期为准）；
8.存在急性或慢性感染，包括：
（1）已知人免疫缺陷病毒（HIV）检测阳性史或已知获得性免疫缺陷综合征病史；
（2）活动性结核感染（根据临床症状、体格检查和/或影像学，以及实验室发现）；
（3）有需要全身治疗的活动性细菌或真菌感染；
（4）乙肝表面抗原、乙肝e抗原、乙肝e抗体及乙肝核心抗体阳性患者；
（5）丙型肝炎患者；
（6）梅毒螺旋体抗体阳性的患者；
9.筛选前14天内接种过新型冠状病毒疫苗或在筛选前3个月内接种过活疫苗或计划在试验期间接种活疫苗者；
10.筛选前4周内接受过主要脏器外科手术（不包括穿刺活检）或出现过显著外伤，或需要在试验期间接受择期手术；
11.在筛选前5年内诊断为其他恶性肿瘤，不包括经过根治的皮肤基底细胞癌、皮肤鳞状细胞癌和/或经过根治切除的原位癌；
12.妊娠期或哺乳期妇女；
13.既往化疗中出现需要血液制品支持的SAE（包括但不限于全血、红细胞、血小板等）；
14.已知有精神疾病、酗酒、吸毒或药物滥用等情况，以及研究者认为不适宜参加本试验者。

Exclusion criteria：

1. Known severe allergic reactions (>= grade 3) to test related drugs (cyclophosphamide, fludarabine, interleukin-2) and their active ingredients and/or any excipients;
2. Have any uncontrollable clinical problems, including but not limited to:
(1) Hypertension with poor drug control (blood pressure >=150/90mmHg in quiet state after medication);
(2) Poorly controlled diabetes mellitus;
(3) Heart disease (Class III/IV congestive heart failure or heart block as defined by the New York Heart Association);
3. The following cases occurred in the 6 months before screening: Deep vein thrombosis or pulmonary embolism; Myocardial infarction; Severe or unstable arrhythmia or angina; Percutaneous coronary intervention, acute coronary syndrome, coronary artery bypass grafting; Cerebrovascular accident, transient ischemic attack, cerebral embolism;
4. Active autoimmune diseases requiring systemic treatment during the study period or organ transplant recipients, or a history of such diseases within the past 2 years;
5. Any immunosuppressive drugs, such as corticosteroids, were used within 14 days prior to enrollment. Physiological doses of glucocorticoids (<=10 mg/ day of prednisone or equivalent) are permitted; Inhaled, intranasal, or topical corticosteroids are permitted;
6. Symptomatic brain metastases. Patients with asymptomatic BMS or stable symptoms after treatment of BMS were eligible to participate in this study if they met all of the following criteria:
(1) Measurable lesions outside the central nervous system, allowing treatment of BMS with radiation or surgery;
(2) The maximum lesion diameter <= 1cm and the number of lesions <= 3 cases;
(3) No meningeal, midbrain, pontine, bulbar or spinal metastasis;
(4) The clinical stable state was maintained for at least 4 weeks before enrollment;
7. TIL anticancer therapy used before collection: chemotherapy, immune checkpoint inhibitors, other investigational drug therapy, or topical therapy to target lesions within the last 4 weeks; Received systemic systemic therapy with Chinese patent drugs with anti-tumor indications or immunomodulatory drugs (including thymosin and interferon) in the past 2 weeks; Received targeted drugs in the past 4 weeks (If the target drug metabolizes with 5 half-lives less than 4 weeks, 5 half-lives shall prevail);
8. Acute or chronic infections are present, including:
(1) A known history of testing positive for human immunodeficiency virus (HIV) or a known history of acquired immunodeficiency syndrome;
(2) Active tuberculosis infection (based on clinical symptoms, physical examination and/or imaging, and laboratory findings);
(3) There is an active bacterial or fungal infection requiring systemic treatment;
(4) Hepatitis B surface antigen, hepatitis B e antigen, hepatitis B e antibody and hepatitis B core antibody positive patients;
(5) Hepatitis C patients;
(6) Patients with positive antibody to treponema pallidum;
9. Patients who have received the novel coronavirus vaccine within 14 days prior to screening or have received live vaccine within 3 months prior to screening or plan to receive live vaccine during the trial;
10. Had major organ surgery (excluding needle biopsy) or significant trauma within 4 weeks prior to screening, or required elective surgery during the trial period;
11. Other malignancies diagnosed within 5 years prior to screening, excluding radical basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or radical excision of carcinoma in situ;
12. Pregnant or lactating patients;
13. SAE requiring blood product support (including but not limited to whole blood, red blood cells, platelets, etc.) occurred during previous chemotherapy;
14. Those with known mental illness, alcohol, drug or substance abuse, and those deemed unfit by the researchers to participate in the study.

研究实施时间：

Study execute time：

从 From 2022-06-01 00:00:00至 To 2025-05-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2022-06-01 00:00:00 至 To 2023-05-31 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	10
Group：	Experimental group	Sample size：	10
干预措施：	回输TIL细胞	干预措施代码：
Intervention：	TIL cells were infused back	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	山东	市(区县)：	青岛
Country：	China	Province：	Shandong	City：	Qingdao
单位(医院)：	青岛大学附属医院	单位级别：	三级甲等
Institution hospital：	The Affiliated Hospital of Qingdao University	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	安全性和耐受性	指标类型：	主要指标
Outcome：	Safety and tolerance	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：	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：

指标中文名：	至缓解时间	指标类型：	次要指标
Outcome：	Time-to-response	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	响应期	指标类型：	次要指标
Outcome：	Duration of response	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：

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：

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	75	岁 years

性别：

女性

Gender：

Female

随机方法（请说明由何人用什么方法产生随机序列）：

非随机

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

N/A

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：	N/A
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）：	未说明
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	Not stated
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：	2022-05-03 07:53:46