ChiCTR2400079704 版本V1.0 版本创建时间2024/01/10 10:37:11 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：

ChiCTR2400079704 

最近更新日期：

Date of Last Refreshed on：

2024-01-10 10:37:05 

注册时间：

Date of Registration：

2024-01-10 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

个体化分子残留病灶应用于肾细胞癌的风险分层、复发监测和药物疗效预测

Public title：

Customized MRD for risk stratification, recurrence monitoring and drug efficacy prediction in renal cell carcinoma

注册题目简写：

English Acronym：

研究课题的正式科学名称：

个体化分子残留病灶应用于肾细胞癌的风险分层、复发监测和药物疗效预测

Scientific title：

Customized MRD for risk stratification, recurrence monitoring and drug efficacy prediction in renal cell carcinoma

研究课题代号(代码)：

Study subject ID：

 RCC-MRD-2023

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：

李多彩 

研究负责人：

任善成 

Applicant：

Li Duocai 

Study leader：

Ren Shancheng 

申请注册联系人电话：

Applicant telephone：

+86 187 2165 5820

研究负责人电话：

Study leader's telephone：

+86 139 1779 3885

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：

896290202@qq.com

研究负责人电子邮件：

Study leader's E-mail：

renshancheng@gmail.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：

上海市黄浦区凤阳路415号

研究负责人通讯地址：

上海市黄浦区凤阳路415号

Applicant address：

No.415 Fengyang Rd.,Huangpu District,Shanghai,China

Study leader's address：

No.415 Fengyang Rd.,Huangpu District,Shanghai,China

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：

海军军医大学第二附属医院(上海长征医院)

Applicant's institution：

The Second Affiliated Hospital of Naval Medical University(Shanghai Changzheng Hospital)

研究负责人所在单位：

海军军医大学第二附属医院(上海长征医院)

Affiliation of the Leader：

The Second Affiliated Hospital of Naval Medical University(Shanghai Changzheng 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：

2023SL056

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：

上海长征医院医学伦理委员会

Name of the ethic committee：

Medical Ethics Committee of Shanghai Changzheng Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

2023-11-27 00:00:00

伦理委员会联系人：

海军军医大学第二附属医院(上海长征医院)

Contact Name of the ethic committee：

The Second Affiliated Hospital of Naval Medical University(Shanghai Changzheng Hospital)

伦理委员会联系地址：

上海市黄浦区凤阳路415号

Contact Address of the ethic committee：

No.415 Fengyang Rd.,Huangpu District,Shanghai,China

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 21 8188 5046

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：

海军军医大学第二附属医院(上海长征医院)

Primary sponsor：

The Second Affiliated Hospital of Naval Medical University(Shanghai Changzheng Hospital)

研究实施负责（组长）单位地址：

上海市黄浦区凤阳路415号

Primary sponsor's address：

No.415 Fengyang Rd.,Huangpu District,Shanghai,China

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)：

Country：

China

Province：

Shanghai

City：

单位(医院)：

海军军医大学第二附属医院(上海长征医院)

具体地址：

上海市黄浦区凤阳路415号

Institution
hospital：

The Second Affiliated Hospital of Naval Medical University(Shanghai Changzheng Hospital)

Address：

No.415 Fengyang Rd.,Huangpu District,Shanghai,China

经费或物资来源：

自筹

Source(s) of funding：

Raise independently

Target disease：

Renal Cell Carcinoma

Target disease code：

研究类型：

观察性研究

Study type：

Observational study

研究所处阶段：

 探索性研究/预试验 

Study phase：

0

研究设计：

队列研究 

Study design：

Cohort study 

研究目的：

1. 根据患者MRD检测结果及预后评分模型，进行风险评分：a) 术前MRD检测联合TNM等预后模型;b) 术后1月MRD检测结果联和UISS等预后模型，并研究不同风险患者所接受的药物治疗是否能降低肿瘤复发率，从而优化患者风险分层，避免过度治疗。 2. 探究MRD术前及术后状态与肾细胞癌根治性手术治疗（包括肾癌根治术、肾部分切除术）后患者出现的疾病复发和转移的相关性，确定MRD临床阈值（包括ctDNA突变数、浓度等）。 3. 比较MRD提示复发和影像学检查（CT、PET-CT）提示复发的时间，验证 MRD检测是否能更早期发现疾病的复发、转移。 4. 观察术后辅助治疗前及治疗期间患者MRD状态，据患者药物反应性与MRD检测结果间关系，比较（a）MRD持续阳性者和阳转阴者二者的预后差异以及（b）MRD持续阴性者和阴转阳者二者的预后差异（c）MRD持续阴性者与持续阳性者的预后差异，以探讨MRD能否作为辅助治疗的近期疗效评价指标，验证MRD阳性病人的术后治疗是否应更为积极，并通过MRD情况实现早期发现、早期换药等。  

Objectives of Study：

1. Performing a risk scoring based on patients' MRD test results and prognostic scoring models: a) preoperative MRD test in conjunction with TNM and other prognostic models; b) 1-month postoperative MRD test results in conjunction with UISS and other prognostic models, and studying whether the drug treatments received by patients with different risks can reduce the rate of tumor recurrence, so as to optimize the patient's risk stratification and avoid over-treatment. 2. To explore the correlation between preoperative and postoperative status of MRD and disease recurrence and metastasis occurring in patients after radical surgical treatments for renal cell carcinoma (including radical nephrectomy and partial nephrectomy for renal carcinoma), and to determine clinical thresholds for MRD (including the number of ctDNA mutations, concentration, etc.). 3. Comparing the time between MRD suggesting recurrence and imaging tests (CT, PET-CT) suggesting recurrence, and verifying whether MRD testing can detect disease recurrence and metastasis at an earlier stage. 4. Observe the MRD status of patients before and during postoperative adjuvant therapy, and according to the relationship between patients' drug responsiveness and MRD results, compare (a) the prognostic difference between those with persistently positive MRD and those with positive-to-negative MRD; (b) the prognostic difference between those with persistently negative MRD and those with negative-to-positive MRD; and (c) the prognostic difference between persistently negative MRD and persistently positive MRD, so as to explore whether MRD can be used as an indicator for evaluating the near-term efficacy of adjuvant therapy, and whether it is a good indicator for evaluating the near-term efficacy of adjuvant therapy. treatment, to verify whether the postoperative treatment of MRD-positive patients should be more aggressive, and to realize early detection and early medication change by MRD status.

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）对本研究已充分了解并自愿签署知情同意书； （2）年龄18岁-至75周岁，男女不限； （3）肿瘤可根治切除，术前胸部CT、腹部增强CT、ECT及PET-CT等未见明显转移灶，术后影像无疾病残留证据； （4）根据美国癌症联合委员会（AJCC）第8版肾癌临床前TNM分期为T1b-T2b期并同时伴有以下特征之一，拟接受肾部分切除术患者： a.影像学检查提示肿瘤恶性度较高，包括肿瘤呈分叶状、合并出血坏死等。 b. 影像学检查或术中见肿瘤位于特殊位置，包括肾门、肾窦部； c.术后肿瘤病理提示包含高恶性程度、高侵袭力的肾细胞癌类型，包括肉瘤性脱分化透明细胞肾细胞癌、集合管癌、肾髓质癌等； d.肾癌UISS预后分级系统评估为中危、高危 （5）根据美国癌症联合委员会（AJCC）第8版肾癌临床前TNM分期为T1b-T4分期并同时伴有以下特征之一，拟接受肾癌根治术患者： b. 术前影像学示肿瘤合并静脉癌栓（膈肌以下）或腹腔淋巴结可疑阳性患者，凡术者判断能根治性切除病灶时，无论患者肿瘤大小，均可纳入。 （6）肿瘤能同时行手术根治的双肾癌或多发性肾癌患者； （7）术式入组比例要求：肾癌根治术与肾部分切除术两种术式占比不低于35%；病理亚型入组比例要求：肾透明细胞癌入组比例不少于70%；

Inclusion criteria

(1) Have been fully informed about the study and voluntarily signed an informed consent form; (2) Age 18 years - to 75 years old, male and female; (3) Tumors could be radically resected, no obvious metastatic foci were seen in preoperative chest CT, abdominal enhanced CT, ECT and PET-CT, and there was no evidence of residual disease in postoperative imaging; (4)Patients who are proposed to undergo partial nephrectomy according to the American Joint Committee on Cancer (AJCC) 8th edition preclinical TNM staging of renal cancer at stage T1b-T2b with one of the following features: a. Imaging studies suggesting a high degree of tumor malignancy, including lobulated tumors and combined hemorrhagic necrosis. b. Tumor located in special location, including renal hilar and renal sinus, as seen on imaging or intraoperatively; c. Postoperative tumor pathology suggests the type of renal cell carcinoma containing high malignancy and invasiveness, including sarcomatoid dedifferentiated clear cell renal cell carcinoma, collecting duct carcinoma, renal medullary carcinoma; d. Renal cancer assessed as intermediate risk or high risk by the UISS prognostic grading system for renal cancer (5) Patients with preclinical TNM staging of renal cancer according to the American Joint Committee on Cancer (AJCC) 8th edition as stage T1b-T4 with one of the following features, who are proposed to undergo radical nephrectomy for renal cancer: a. Intermediate-risk and high-risk as assessed by the UISS prognostic grading system for renal cancer; b. Patients with preoperative imaging showing tumor combined with venous cancerous embolus (below the diaphragm) or suspected positive abdominal lymph nodes can be included regardless of the size of the patient's tumor whenever the operator judges that the lesion can be radically resected. (6) Patients with double kidney cancer or multiple kidney cancers whose tumors can undergo simultaneous radical surgery; (7) Requirement for the proportion of operative modality enrollment: no less than 35% of the two types of radical nephrectomy and partial nephrectomy for renal cancer; Requirement for the proportion of pathologic subtype enrollment: no less than 70% of the proportion of renal clear cell carcinoma enrollment;

排除标准：

（1）患者肿瘤已发生远处转移，包括无法根治性切除的远处淋巴结转移、(除同侧肾上腺外)脏器转移与骨转移； （2）双肾癌且无法同时根治； （3）拟接受肾部分切除术，但UISS评分为低危（即T1期、核分级1-2级、ECOG=0）的患者； （4）合并全身其他肿瘤； （5）术前已接受抗肿瘤治疗； （6）既往接受过肾部分切除术或根治术患者； （7）随访时间少于12个月的非复发患者； （8）患有一般情况差，存在以下情况之一：包括严重精神障碍、心血管疾病、活动性感染、3个月内骨髓移植、器官功能明显异常； （9）在过去三个月中参与其他临床研究或以前使用任何基因治疗产品的治疗； （10）其他研究人员认为可能影响实验结果或者有违伦理的情况。

Exclusion criteria：

(1) The patient's tumor has developed distant metastasis, including distant lymph node metastasis that cannot be radically resected, organ metastasis (except for the ipsilateral adrenal gland) and bone metastasis; (2) Bilateral renal cancer that cannot be treated at the same time; (3) Patients who are proposed to undergo partial nephrectomy but have a low-risk UISS score (i.e., stage T1, nuclear classification 1-2, ECOG=0); (4) Combination of other tumors throughout the body; (5) Preoperative antitumor therapy; (6) Patients who have previously undergone partial nephrectomy or radical nephrectomy; (7) Non-recurrent patients with less than 12 months of follow-up; (8) Suffering from poor general condition with the presence of one of the following conditions: including severe mental disorders, cardiovascular disease, active infections, bone marrow transplantation within 3 months, or significant abnormalities in organ function; (9) Participation in other clinical studies or previous treatment with any gene therapy product within the last three months; (10) Other conditions that the researchers believe may affect the experimental results or violate ethics.

研究实施时间：

Study execute time：

从 From 2024-01-15 00:00:00至 To 2029-05-31 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2024-01-15 00:00:00 至 To 2024-06-30 00:00:00  

干预措施：

Interventions：

组别：

观察组

样本量：

200

Group：

Observation group

Sample size：

干预措施：

无 拟观察结果包括： 1. MRD检测结果 2.MRD术前及术后状态 3.MRD和影像学检查（CT、PET-CT）提示复发时间的差别 4.术后辅助治疗前及治疗期间患者MRD状态，据患者药物反应性与MRD检测结果间关系

干预措施代码：

Intervention：

None We aim to observe: 1. Patients' MRD test results 2.Preoperative and postoperative status of Patients' MRD 3.Comparison between the time of suggested recurrence by MRD and imaging (CT, PET-CT) 4.The MRD status of patients before and during postoperative adjuvant therapy, according to the relationship between patients' drug responsiveness and MRD test results.

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)：

海军军医大学第二附属医院(上海长征医院) 

单位级别：

三甲 

Institution
hospital：

The Second Affiliated Hospital of Naval Medical University(Shanghai Changzheng Hospital)

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 浙江 

市(区县)：

  

Country：

China 

Province：

Zhejiang 

City：

 

单位(医院)：

宁波大学附属第一医院 

单位级别：

三甲 

Institution
hospital：

The First Affiliated Hospital of Ningbo University

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 江苏 

市(区县)：

  

Country：

China 

Province：

Jiangsu 

City：

 

单位(医院)：

苏州大学附属第一医院 

单位级别：

三甲 

Institution
hospital：

The First Affiliated Hospital of Soochow University

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 广东 

市(区县)：

  

Country：

China 

Province：

Guangdong 

City：

 

单位(医院)：

广州医科大学附属第一医院 

单位级别：

三甲 

Institution
hospital：

The First Hospital of Guangzhou Medical University

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 浙江 

市(区县)：

  

Country：

China 

Province：

Zhejiang 

City：

 

单位(医院)：

湖州市中心医院 

单位级别：

三甲 

Institution
hospital：

Huzhou Central Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

分子残留病灶

指标类型：

主要指标

Outcome：

Molecular residual disease

Type：

Primary indicator

测量时间点：

术前0-14天，术后1个月，术后6个月，术后12个月，术后18个月，术后24个月，术后30个月，术后36个月，术后42个月，术后48个月，术后54个月，术后60个月

测量方法：

Measure time point of outcome：

0-14 days before surgery, 1 month after operation, 6 months after operation, 12 months after operation, 18 months after operation, 24 months after operation, 30 months afteroperation, 36 months after operation, 42 months after operation, 48 months after operation, 54 months after operation, 60 months after operation

Measure method：

指标中文名：

无复发生存期

指标类型：

主要指标

Outcome：

recurrence-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：

MRD 先于影像学提示复发转移的预警时间

指标类型：

次要指标

Outcome：

warning time of MRD prior to imaging suggesting recurrent metastasis

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

ctDNA 状态持续时间

指标类型：

次要指标

Outcome：

ctDNA status duration

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：

血液

组织：

静脉

Sample Name：

Blood

Tissue：

Vein

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：

肿瘤

组织：

手术标本

Sample Name：

Tumor

Tissue：

Surgical specimens

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：

正在进行

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)：

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

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）：

试验完成后6个月内公开，并在ResMan临床试验管理平台上上传

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

The trial was released within 6 months after completion and uploaded on the ResMan clinical trial management platform

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：

各中心的数据由该中心的负责人负责采集，在所有患者数据采集完成后将原数据提交给海军军医大学附属第二医院负责人，由海军军医大学附属第二医院泌尿外科的工作人员负责保存。

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

The data of each center shall be collected by the person in charge of the center. After the data collection of all patients is completed, the original data shall be submitted to the person in charge of the The Second Affiliated Hospital of Naval Medical University(Shanghai Changzheng Hospital) and kept by the staff of Urology Department.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2024-01-10 10:37:05