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：	ChiCTR2300068555
最近更新日期： Date of Last Refreshed on：	2023-05-27 18:04:50
注册时间： Date of Registration：	2023-02-23 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	基于免疫细胞亚群及ctDNA靶向测序探索mCRPC患者免疫检查点抑制剂治疗的疗效预测标志物的研究
Public title：	A clinical study on predictive markers of immune checkpoint inhibitor therapy in mCRPC patients based on immune cell subsets and ctDNA targeted sequencing
注册题目简写：
English Acronym：
研究课题的正式科学名称：	基于免疫细胞亚群及ctDNA靶向测序探索mCRPC患者免疫检查点抑制剂治疗的疗效预测标志物的研究
Scientific title：	A clinical study on predictive markers of immune checkpoint inhibitor therapy in mCRPC patients based on immune cell subsets and ctDNA targeted sequencing
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：	陶涵洋	研究负责人：	董柏君
Applicant：	Tao Hanyang	Study leader：	Dong Baijun
申请注册联系人电话： Applicant telephone：	+86 193 7060 2583	研究负责人电话： Study leader's telephone：	+86 137 6121 0771
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：	thy1024658955@163.com	研究负责人电子邮件： Study leader's E-mail：	dongbaijun@renji.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：	上海交通大学医学院学生公寓	研究负责人通讯地址：	上海市浦东新区浦建路160号
Applicant address：	Shanghai Jiao Tong University School of Medicine student apartment	Study leader's address：	160 Pujian Road, Pudong New Area, 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：	上海交通大学医学院附属仁济医院
Applicant's institution：	Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
研究负责人所在单位：	上海交通大学医学院附属仁济医院
Affiliation of the Leader：	Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University

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：	KY2021-176-B	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：	上海交通大学医学院附属仁济医院伦理委员会
Name of the ethic committee：	Shanghai Jiao Tong University School of Medicine, Ren Ji Hospital Ethics Committee
伦理委员会批准日期： Date of approved by ethic committee：	2022-07-20 00:00:00
伦理委员会联系人：	陆麟
Contact Name of the ethic committee：	Lu Lin
伦理委员会联系地址：	上海市浦东新区浦建路160号
Contact Address of the ethic committee：	160 Pujian Road, Pudong New Area, Shanghai
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 21 68383364	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：

上海交通大学医学院附属仁济医院

Primary sponsor：

Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University

研究实施负责（组长）单位地址：

上海市浦东新区浦建路160号

Primary sponsor's address：

160 Pujian Road, Pudong New Area, 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)：	浦东新区
Country：	China	Province：	Shanghai	City：	Pudong New Area
单位(医院)：	上海交通大学医学院附属仁济医院	具体地址：	浦建路160号
Institution hospital：	Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University	Address：	160 Pujian Road

经费或物资来源：

百济神州

Source(s) of funding：

Beigene, Ltd.

研究疾病：

前列腺癌

Target disease：

prostate 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：

I期临床试验

Study phase：

1

研究设计：

单臂

Study design：

Single arm

研究目的：

探究免疫检查点抑制剂治疗对于具有携带DNA缺陷修复基因突变的既往接受过一线新型内分泌治疗失败的mCRPC患者的疗效；分析mCRPC患者接受免疫检查点抑制剂治疗前后，外周血中各免疫细胞亚群的占比以及多基因靶向测序情况与免疫检查点抑制剂治疗疗效的关系，探究其疗效预测标志物。

Objectives of Study：

To explore the efficacy of immune checkpoint inhibitor therapy in mCRPC patients with DNA defect repair gene mutations who have previously failed first-line endocrine therapy. To analyze the relationship between the proportion of immune cell subsets in peripheral blood and multi-gene targeting sequencing of mCRPC patients before and after receiving immune checkpoint inhibitor treatment and the therapeutic efficacy of immune checkpoint inhibitor, and explore the therapeutic efficacy prediction markers.

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. According to the EAU-EANM-ESTRO-ESUR-SIOG2020 guidelines, the clinical diagnosis is mCRPC, and at least 1, <= 2 new endocrine drug treatments have failed (abiraterone acetate or new AR antagonists: such as enzalutamide, Apalutamide, SHR3680, etc.) patients; patients who failed chemotherapy treatment (imaging progression or PSA progression) were allowed to enroll; patients who were intolerant or refused chemotherapy were allowed to enroll;
2. Prostate adenocarcinoma is confirmed by histological examination and small cell carcinoma is excluded, and the diagnosis must be stated in the pathology report and confirmed by the researcher;
3. Evidence of metastatic disease in imaging examinations: soft tissue lesion metastases shown by computed tomography (CT)/magnetic resonance imaging (MRI)/PET-CT and/or bone lesions confirmed by bone scan, and other organs Metastasis, including but not limited to liver, lung, brain, etc.;
4. Patients with germline or systemic mutations of DNA defect repair genes confirmed by next-generation gene sequencing, with previous test results at least including BRCA2, BRCA1, ATM, PALB2, FANCL, RAD51B, RAD51C, RAD51D, BRIP1, BRAD1, CHEK1, CHEK2, Germline and systemic mutation detection of CDK12 and RAD54L;
5. ECOG score 0-2 points;
6. The patient has normal organ function, WBC >= 3000/mm3 or absolute neutrophil count greater than 1500/mm3, platelets greater than 100×10^9/L, hemoglobin greater than 100 g/L, AST and ALT less than 1.5 ULN (the first medication Within 7 days), AKP is less than 2.5ULN, if accompanied by bone metastasis, it is less than 5ULN, and serum creatinine is less than 1.25ULN;
7. When signing the informed consent form, the age is equal to or greater than 18 years old and less than 75 years old;
8. The investigator expects the patient's survival to be greater than 3 months;
9. The patient agrees and has the ability to follow the planned research visits, provide blood samples before and after treatment, provide clinical information and cooperate with other research steps.

排除标准：

1. 已知有其他恶性肿瘤正在进展或需要积极治疗； 2. 患有活动性自身免疫病，在过去两年中需要全身治疗； 3. 有需要类固醇治疗的（非感染性）肺炎病史，或目前患有肺炎； 4. 患有先天或后天免疫功能缺陷（如 HIV 感染者）； 5. 患有活动性肝炎（乙肝参考：HBsAg阳性且 HBV DNA≥500 IU/ml；丙肝参考：HCV抗体阳性且HCV病毒拷贝数>正常值上限）； 6. 受试者在研究治疗开始前至少14天必须从需全身麻醉的大手术或严重创伤中痊愈； 7. ≥2级与盆腔靶向治疗相关的毒性（如：放射性肠炎）缓解后不到1年； 8. 患骨髓异常增生综合征（MDS）/急性髓系白血病（AML）或有此类病史； 9. 有症状性充血性心力衰竭（纽约心脏协会III级或IV级心脏病）； 10. 接受过先前的同种异体骨髓移植或双脐带移植（dUCBT）或实体器官移植； 11. 入组前2周内接受过细胞色素P450 3A4酶（CYP3A4）强抑制剂：伊曲康唑、克拉霉素、伏立康唑、泰利霉素、沙奎那韦和利托那韦等； 12. 无法获得研究所需临床信息(如患者失访)； 13. 其他研究者认为不适合入组的情况，如酗酒、药物滥用、其他的严重疾病（含精神疾病）需要合并治疗，有严重的实验室检查异常，伴有家庭或社会等因素，会影响到患者的安全。

Exclusion criteria：

1. It is known that other malignant tumors are progressing or require active treatment; 2. Suffering from active autoimmune disease, requiring systemic treatment in the past two years; 3. Have a history of (non-infectious) pneumonia requiring steroid treatment, or currently suffer from pneumonia; 4. Suffering from congenital or acquired immune deficiency (such as HIV infection); 5. Suffering from active hepatitis (hepatitis B reference: HBsAg positive and HBV DNA ≥ 500IU/ml; hepatitis C reference: HCV antibody positive and HCV virus copy number > upper limit of normal value); 6. The subject must recover from major surgery or severe trauma requiring general anesthesia at least 14 days before the start of the study treatment; 7. Grade >= 2 toxicity related to pelvic targeted therapy (such as: radiation enteritis) less than 1 year after remission; 8. Suffer from myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or have such medical history; 9. Symptomatic congestive heart failure (New York Heart Association Class III or IV heart disease); 10. Received previous allogeneic bone marrow transplantation or double umbilical cord transplantation (dUCBT) or solid organ transplantation; 11. Received strong cytochrome P450 3A4 enzyme (CYP3A4) inhibitors within 2 weeks before enrollment: itraconazole, clarithromycin, voriconazole, telithromycin, saquinavir and ritonavir, etc.; 12. The clinical information required for the study cannot be obtained (such as patients lost to follow-up); 13. Other conditions that the researchers think are not suitable for enrollment, such as alcoholism, drug abuse, other serious diseases (including mental illness) that require combined treatment, severe laboratory abnormalities, and family or social factors, which will affect to patient safety.

研究实施时间：

Study execute time：

从 From 2023-03-01 00:00:00至 To 2026-01-01 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2023-03-01 00:00:00 至 To 2024-01-01 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	20
Group：	Experimental group	Sample size：	20
干预措施：	替雷利珠单抗	干预措施代码：
Intervention：	Tirelizumab	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)：
Country：	China	Province：	Shanghai	City：
单位(医院)：	上海交通大学医学院附属仁济医院	单位级别：	三甲
Institution hospital：	Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	PSA缓解率	指标类型：	主要指标
Outcome：	PSA Response 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：	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：	安全性	指标类型：	次要指标
Outcome：	safety	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	疗效预测标志物	指标类型：	附加指标
Outcome：	Efficacy prediction markers	Type：	Additional 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：	外周血	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：

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)：

N/A

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）：	点击下载
Calculated Results after the Study Completed(upload file)：	download

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）：	无
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	none
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：	CRF
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	CRF
数据与安全监察委员会： Data and Safety Monitoring Committee：	有/Yes
注册人： Name of Registration：	2023-02-23 10:45:41