ChiCTR2400090274 版本V1.0 版本创建时间2024/09/26 15:30:14 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：

ChiCTR2400090274 

最近更新日期：

Date of Last Refreshed on：

2024-09-26 15:30:10 

注册时间：

Date of Registration：

2024-09-26 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

放疗序贯多纳非尼和特瑞普利单抗治疗HCC局限性转移患者的有效性和安全性临床研究

Public title：

Clinical study on the efficacy and safety of sequential radiotherapy with donafenib and trastuzumab in the treatment of localized metastatic HCC

注册题目简写：

English Acronym：

研究课题的正式科学名称：

放疗序贯多纳非尼和特瑞普利单抗治疗HCC局限性转移患者的有效性和安全性临床研究

Scientific title：

Clinical study on the efficacy and safety of sequential radiotherapy with donafenib and trastuzumab in the treatment of localized metastatic HCC

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：

吴志峰 

研究负责人：

吴志峰 

Applicant：

Zhifeng Wu 

Study leader：

Zhifeng Wu 

申请注册联系人电话：

Applicant telephone：

+86 159 0086 6150

研究负责人电话：

Study leader's telephone：

+86 159 0086 6150

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：

wu.zhifeng@zs-hospital.sh.cn

研究负责人电子邮件：

Study leader's E-mail：

wu.zhifeng@zs-hospital.sh.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：

徐汇区斜土路1609号

研究负责人通讯地址：

徐汇区斜土路1609号

Applicant address：

No. 1609 Xietu Road, Xuhui District

Study leader's address：

No. 1609 Xietu Road, Xuhui District

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：

复旦大学附属中山医院

Applicant's institution：

ZHONGSHAN HOSPITAL

研究负责人所在单位：

复旦大学附属中山医院

Affiliation of the Leader：

ZHONGSHAN 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：

B2024-314R

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：

复旦大学附属中山医院医学伦理委员会

Name of the ethic committee：

Ethics Committee of Zhongshan Hospital Fudan University

伦理委员会批准日期：

Date of approved by ethic committee：

2024-08-28 00:00:00

伦理委员会联系人：

杨梦婕

Contact Name of the ethic committee：

Mengjie Yang

伦理委员会联系地址：

上海市徐汇区枫林路180号

Contact Address of the ethic committee：

180 Fenglin Road, Xuhui District, Shanghai

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 21 3158 7871

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：

复旦大学附属中山医院

Primary sponsor：

Zhongshan Hospital

研究实施负责（组长）单位地址：

上海市徐汇区枫林路180号

Primary sponsor's address：

180 Fenglin Road, Xuhui District, 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)：

Country：

China

Province：

Shanghai

City：

单位(医院)：

复旦大学附属中山医院

具体地址：

上海市徐汇区枫林路180号

Institution
hospital：

Zhongshan Hospital

Address：

180 Fenglin Road, Xuhui District, Shanghai

经费或物资来源：

苏州泽璟生物制药股份有限公司，上海君实生物医药科技股份有限公司

Source(s) of funding：

Suzhou Zelgen Biopharmaceuticals Co.,Ltd,Shanghai Junshi Biosciences Co., Ltd.

Target disease：

Hepatocellular Carcinoma

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：

本研究为一项单中心、开放标签、单臂、探索性研究评价放疗序贯多纳非尼和免疫治疗HCC局限性转移患者的安全性和有效性。  

Objectives of Study：

This study is a single center, open label, single arm, exploratory study evaluating the safety and efficacy of sequential radiotherapy with donafenib and immunotherapy in patients with localized metastatic HCC.

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 ~ 75岁（含界值），男女不限； 2)临床诊断为肝细胞肝癌或病理学证实为肝细胞癌，且不可手术的肝细胞癌患者； 3)有肝外转移，肿瘤分期为 CNLC IIIb 期，且符合局限转移的定义。 局限性转移定义（模拟小细胞肺癌“局限期”分期定义原则）：全部病灶（肝外转移灶+/-2处以内肝内病灶，不限于寡转移），可被放疗靶区一体纳入，经放疗计划评估患者能耐受并完成，且不会出现严重并发症。 参照传统淋巴瘤分期和次全淋巴结区照射技术，以及目前放疗技术进步条件下可耐受最大受照范围，按转移部位、数目等特征将肝外转移灶分为8个区域；进一步，界定局限转移HCC为：病灶区域总数（2处以内的肝内病灶，作为单独一个区域）≤3区域）。具体为如下3类： A横膈以上局限性转移（分区；A1区. 颈部淋巴结转移， A2区. 纵隔淋巴结转移，A3区. 2处以内肺转移灶，A4区. 2处以内的横隔上非脊椎骨转移灶）； B横膈以下局限性转移（B1区. 肝门及肾门以上后腹膜淋巴结转移，B2区. 肾门以下至髂总动脉后腹膜淋巴结转移，B3区. 肾上腺转移，B4区. 2处以内膈下非脊椎骨转移灶）； C横隔两侧局限性转移，横隔两侧病灶区域总数≤3个区域。 （注：鉴于HCC脑及或脊椎转移相关神经功能及治疗原则特异，本研究不予纳入）。 4)既往无多纳非尼/仑伐替尼或免疫药物治疗史或治疗时间距入组间隔≥4周； 5)既往未经过放射治疗； 6)术后复发或局部治疗后进展的HCC患者（术后辅助治疗> 6个月，且末次介入、消融治疗结束> 4周） 7)至少有 1 处影像学可测量病灶； 可测量病灶定义：最长径≥10 mm的非淋巴性病变或短轴≥15 mm的淋巴结性病变； 既往接受过介入或消融治疗，且RECIST v1.1评价为进展，最长径≥10 mm的病灶视为可测量病灶； 8)肝功能Child-Pugh评分≤7分； 9)东部肿瘤协作组（ECOG）体力状况（PS）评分 0-1分； 10)预计生存期不少于3个月； 11)HBV感染者，入组前14天内HBV-DNA若为≥1000 copies/ml，则先进行抗病毒治疗，降至<1000 copies/ml再进入研究，并继续抗病毒治疗和监测肝功能和血清HBV-DNA水平等； 12)具有充足的器官功能储备，治疗前14天内实验室检查值必须符合以下标准： a)血常规检查： ?Hb≥80 g/L ?ANC≥1.5×109 /L ?PLT≥50×109 /L b)生化检查： ?ALB ≥30g/L ?ALT和AST<5×ULN ?TBIL ≤1.5×ULN ?肌酐 ≤1.5×ULN或肌酐清除率（Ccr）≥50 mL/min c)电解质基本正常或经治疗后正常； d)尿蛋白<2+或24小时尿蛋白定量检测≤1.0 g/L（对于尿蛋白≥2+的患者，应当进行24小时尿蛋白定量检测必须≤1.0 g/L方可入选）； e)凝血功能： ?国际标准比值（INR）或凝血酶原时间（PT）≤1.5×ULN ?活化部分凝血时间（aPTT）≤1.5×ULN 13)患者自愿入组，能够提供书面知情同意，且能理解和遵从试验方案服药、随访。

Inclusion criteria

1) Age range of 18 to 75 years old (including threshold), male or female not limited; 2) Patients with hepatocellular carcinoma clinically diagnosed as hepatocellular carcinoma or pathologically confirmed as hepatocellular carcinoma, who cannot undergo surgery; 3) There is extrahepatic metastasis, the tumor stage is CNLC IIIb, and it meets the definition of localized metastasis. Definition of limited metastasis (simulating the staging principle of small cell lung cancer "limited phase"): All lesions (intrahepatic lesions within+/-2 extrahepatic metastases, not limited to oligometastases) can be included in the radiotherapy target area, and the patient can tolerate and complete the radiotherapy plan without serious complications. Referring to traditional lymphoma staging and subtotal lymph node irradiation techniques, as well as the maximum tolerable radiation range under current advances in radiotherapy technology, extrahepatic metastases are divided into 8 regions based on characteristics such as metastasis site and number; Furthermore, the definition of localized metastatic HCC is: the total number of lesion areas (within 2 intrahepatic lesions as a single area) ≤ 3 areas. Specifically, there are three categories: Localized metastasis above the diaphragm (zone A1) Cervical lymph node metastasis, A2 area Mediastinal lymph node metastasis, A3 area Two lung metastases within A4 area Non spinal metastases in the transverse septum within 2 locations; Localized metastasis below the diaphragm (B1 area, retroperitoneal lymph node metastasis above the hepatic and renal hilum, B2 area) Lymph node metastasis from the renal hilum to the retroperitoneum of the common iliac artery, B3 area Adrenal gland metastasis, B4 area 2 subphrenic non spinal metastases); Localized metastasis on both sides of the transverse septum, with a total of ≤ 3 lesion areas on both sides of the transverse septum. (Note: Due to the specific neurological functions and treatment principles related to HCC brain and/or spinal metastases, this study is not included). 4) No previous history of treatment with donafenib/lenvatinib or immunotherapy, or a treatment interval of ≥ 4 weeks from enrollment; 5) Has not undergone radiation therapy in the past; 6) HCC patients with postoperative recurrence or progression after local treatment (postoperative adjuvant therapy>6 months, and last intervention or ablation treatment completed>4 weeks) 7) At least one measurable lesion on imaging; Measurable lesion definition: Non lymphoid lesions with a longest diameter ≥ 10 mm or lymph node lesions with a short axis ≥ 15 mm; Previously received intervention or ablation therapy, and RECIST v1.1 evaluation indicates progression. Lesions with a longest diameter ≥ 10 mm are considered measurable lesions; 8) Liver function Child Pugh score ≤ 7 points; 9) The physical condition (PS) score of the Eastern Cancer Collaboration Group (ECOG) is 0-1 points; 10) Expected survival period is not less than 3 months; 11) For HBV infected individuals, if HBV-DNA is ≥ 1000 copies/ml within 14 days before enrollment, antiviral treatment should be carried out first to reduce it to<1000 copies/ml before entering the study, and antiviral treatment and monitoring of liver function and serum HBV-DNA levels should be continued; 12) Having sufficient organ function reserves, laboratory test values within 14 days before treatment must meet the following standards: a) Blood routine examination: ?Hb≥80 g/L ?ANC≥1.5×109 /L ?PLT≥50×109 /L b) Biochemical examination: ?ALB ≥30g/L ALT and AST<5 × ULN ?TBIL ≤1.5×ULN Creatinine ≤ 1.5 × ULN or creatinine clearance rate (Ccr) ≥ 50 mL/min c) Electrolytes are basically normal or normal after treatment; d) Urinary protein<2+or 24-hour urinary protein quantification test ≤ 1.0 g/L (for patients with urinary protein ≥ 2+, 24-hour urinary protein quantification test must be ≤ 1.0 g/L to be selected); e) Coagulation function: International standard ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN Activated partial clotting time (aPTT) ≤ 1.5 × ULN 13) The patient voluntarily enrolled, provided written informed consent, and understood and followed the trial protocol for medication and follow-up.

排除标准：

1)病理确诊为肝细胞癌-肝内胆管癌（HCC-ICC）混合型或纤维板层样肝细胞癌； 2)既往接受过肝移植； 3)既往接受过系统治疗（除外抗病毒治疗）； 4)多发（结节数量≥3个）或弥散性肝内结节，脑转移及脊椎骨转移（鉴于其特异的相关神经功能及治疗原则，本研究不予纳入）； 5)既往2年内接受过放射治疗； 6)5年内患有其它恶性肿瘤，除非患者接受过可能的治愈性治疗并且5年内无该疾病存在的证据，但该时间要求（即5年内）不适用于已获成功切除的皮肤基底细胞癌、皮肤鳞状细胞癌、浅表膀胱癌、宫颈原位癌或其他原位癌患者； 7)既往有严重精神病; 8)患有影响研究药物吸收、分布、代谢或清除的疾病（如严重呕吐、慢性腹泻、肠梗阻、吸收障碍等）； 9)患者已知或疑似对酪氨酸激酶抑制剂（TKI）类药物有过敏史，或对研究药物的辅料过敏者； 10)存在难以控制的肝性脑病，肝肾综合征，腹水，胸腔积液或心包积液； 11)有活动性出血或凝血功能异常，具有出血倾向或正在接受溶栓、抗凝或抗血小板治疗; 12)既往4周内有消化道出血病史或具有明确的胃肠道出血倾向（如：已知有局部活动性溃疡病灶、大便潜血++以上，如持续大便潜血+，应进行胃镜检查），或研究者判定的可能引起消化道出血的其它状况（如严重的胃底/食管静脉曲张）； 13)既往6个月内出现过胃肠道穿孔，腹部瘘管或腹腔脓肿； 14)既往6个月内出现过血栓形成或血栓栓塞事件，如脑卒中和/或短暂性脑缺血发作、深静脉血栓形成、肺栓塞等； 15)有显著临床意义的心血管疾病，包括但不限于既往6个月内急性心肌梗死、严重/不稳定型心绞痛或者冠脉搭桥术，充血性心力衰竭（纽约心脏病协会NYHA分级>2级），控制不佳或需要起搏器治疗的心律失常，药物未能控制的高血压（收缩压≥140 mmHg和/或舒张压≥90 mmHg）； 16)活动性感染，包括： ?艾滋病病毒（HIV）（HIV1/2抗体）阳性； ?活动性丙型肝炎（HCV抗体阳性或HCV-RNA≥103 copies/ml且肝功能异常）； ?活动性合并感染乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）； ?活动性结核病； ?其它无法控制的活动性感染（CTCAE V5.0 >2级）； 17)其它显著的临床和实验室异常，研究者认为影响安全性评价，如：无法控制的糖尿病、慢性肾病、II级或以上周围神经病变（CTCAE V5.0）、甲状腺功能异常等； 18)妊娠或者哺乳期妇女，以及具有生育能力的女性或男性患者不愿或无法采取有效的避孕措施者； 19)既往6个月内有酒精、精神类药物或其它药物滥用史； 20)无法遵循研究方案接受治疗或按期随访； 21)其他任何研究者认为不能入组者。

Exclusion criteria：

1) Pathological diagnosis of hepatocellular carcinoma intrahepatic cholangiocarcinoma (HCC-ICC) mixed or fibrolamellar hepatocellular carcinoma; 2) Previously received liver transplantation; 3) Previously received systemic therapy (excluding antiviral therapy); 4) Multiple (≥ 3 nodules) or diffuse intrahepatic nodules, brain metastases, and spinal metastases (due to their specific neurological functions and treatment principles, this study is not included); 5) Received radiation therapy within the past 2 years; 6) Other malignant tumors within 5 years, unless the patient has received possible curative treatment and there is no evidence of the disease within 5 years, but this time requirement (that is, within 5 years) does not apply to patients with skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer carcinoma, cervical carcinoma in situ or other carcinoma in situ who have been successfully removed; 7) Having a history of severe mental illness; 8) Suffering from diseases that affect the absorption, distribution, metabolism, or clearance of research drugs (such as severe vomiting, chronic diarrhea, intestinal obstruction, absorption disorders, etc.); 9) Patients who are known or suspected to have a history of allergies to tyrosine kinase inhibitors (TKIs) or are allergic to excipients of the study drug; 10) There are uncontrollable hepatic encephalopathy, hepatorenal syndrome, ascites, pleural effusion or pericardial effusion; 11) Has active bleeding or coagulation dysfunction, has a tendency to bleed, or is currently receiving thrombolysis, anticoagulation, or antiplatelet therapy; 12) Within the past 4 weeks, there has been a history of gastrointestinal bleeding or a clear tendency towards gastrointestinal bleeding (such as known local active ulcer lesions, fecal occult blood++, and if persistent fecal occult blood+, gastroscopy should be performed), or other conditions determined by the researcher that may cause gastrointestinal bleeding (such as severe gastric fundus/esophageal varices); 13) Within the past 6 months, there has been gastrointestinal perforation, abdominal fistula, or abdominal abscess; 14) Has experienced thrombosis or thromboembolic events within the past 6 months, such as stroke and/or transient ischemic attack, deep vein thrombosis, pulmonary embolism, etc; 15) Cardiovascular diseases with significant clinical significance, including but not limited to acute myocardial infarction, severe/unstable angina, or coronary artery bypass surgery within the past 6 months, congestive heart failure (NYHA classification>2), poorly controlled or pacemaker requiring arrhythmias, and uncontrolled hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg); 16) Active infections, including: ? AIDS virus (HIV/2 antibody) positive; Active hepatitis C (HCV antibody positive or HCV-RNA ≥ 103 copies/ml with abnormal liver function); Active co infection with hepatitis B virus (HBV) and hepatitis C virus (HCV); ? Active tuberculosis; Other uncontrollable active infections (CTCAE V5.0>Level 2); 17) Other significant clinical and laboratory abnormalities, which the researchers think affect the safety evaluation, such as uncontrollable diabetes, chronic kidney disease, grade II or above peripheral neuropathy (CTCAE V5.0), thyroid dysfunction, etc; 18) Pregnant or lactating women, as well as female or male patients with fertility who are unwilling or unable to take effective contraceptive measures; 19) History of alcohol, psychotropic or other substance abuse within the past 6 months; 20) Unable to follow the research protocol for treatment or scheduled follow-up; 21) Any other researcher who deems it ineligible for inclusion.

研究实施时间：

Study execute time：

从 From 2024-10-01 00:00:00至 To 2027-09-01 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2024-10-01 00:00:00 至 To 2027-09-01 00:00:00  

干预措施：

Interventions：

组别：

放疗序贯多纳非尼和特瑞普利单抗

样本量：

25

Group：

Sequential radiotherapy with Donafenib and Triprolizumab

Sample size：

干预措施：

放疗： 入组后两周内开始放疗，每周5次。使用调强放射治疗（IMRT）技术, 包括螺旋断层放疗（TOMO）。照射靶区与剂量： 肿瘤（GTV，包括转移灶及肝内原发灶）总剂量DT 30-60Gy+/- 累及淋巴引流区（CTV）总剂量45-50Gy，GTV分次剂量1.7-6Gy，共10-30分次。危及器官（OAR）剂量限量(按BED等换算为2Gy剂量限量)：Liver-GTV平均剂量＜28～30 Gy；胃和小肠最大剂量均应﹤54Gy，胃V45＜45%，小肠V50≤5%。双肾平均剂量≤15Gy；脊髓最大剂量﹤45Gy。 甲苯磺酸多纳非尼片： 首次放疗结束两周后，且研究者评估患者的全身情况和肝功能恢复后开始使用；多纳非尼药物剂量与用法：起始剂量0.1g bid，每日2次，一周后改为0.2g bid，空腹（餐前1小时或餐后2小时）口服；直至出现下列任意一种情况，以先发生者为准：①受试者出现不能耐受的毒性反应，且经剂量调整后仍未缓解；②受试者出现影像学 证实的疾病进展或因其它原因退出研究。 特瑞普利单抗： 与多纳非尼同时开始给药，输注剂量为240mg，每3周一次，治疗6个月，后续根据患者情况研究者判定是否继续使用。

干预措施代码：

Intervention：

Radiation therapy will begin within two weeks of enrollment, with five sessions per week. Use intensity modulated radiation therapy (IMRT) techniques, including spiral tomotherapy (TOMO). Radiation target area and dose: The total dose of tumor (GTV, including metastases and primary liver lesions) is DT 30-60Gy+/-, and the total dose of lymphatic drainage area (CTV) involved is 45-50Gy. The GTV is divided into 10-30 doses of 1.7-6Gy. Organ at risk (OAR) dose limit (converted to 2Gy dose limit based on BED): Liver GTV average dose<28-30 Gy; The maximum dose for both the stomach and small intestine should be less than 54Gy, V45 for the stomach should be less than 45%, and V50 for the small intestine should be less than or equal to 5%. The average dose for both kidneys is ≤ 15Gy; The maximum dose to the spinal cord is less than 45 Gy. Toluene sulfonic acid donafenib tablets: Two weeks after the first radiotherapy is completed, and the researcher evaluates the patient's overall condition and liver function recovery before starting to use it; Dosage and Administration of Donafenib: The initial dose is 0.1g bid, taken twice a day, and changed to 0.2g bid after one week. It is taken orally on an empty stomach (1 hour before or 2 hours after meals); Until any of the following situations occur, whichever occurs first: ① The subject experiences intolerable toxic reactions that have not been relieved after dose adjustment; ② The subject withdrew from the study due to imaging confirmed disease progression or other reasons. Triprolizumab: Administer at the same time as Donafenib, with an infusion dose of 240mg every 3 weeks for 6 months. The researcher will determine whether to continue using the medication based on the patient's condition.

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)：

复旦大学附属中山医院 

单位级别：

三甲 

Institution
hospital：

Zhongshan Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

客观缓解率

指标类型：

主要指标

Outcome：

Objective 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：

总生存期

指标类型：

次要指标

Outcome：

overall survival

Type：

Secondary indicator

测量时间点：

第一次治疗开始至死亡

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：

第一次治疗开始至疾病进展或死亡

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：

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：

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

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：

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

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：

  2024-09-26 15:30:10