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：	ChiCTR2600123864
最近更新日期： Date of Last Refreshed on：	2026-04-30 14:51:39
注册时间： Date of Registration：	2026-04-30 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	呋喹替尼联合贝莫苏拜单抗对比呋喹替尼三线治疗晚期转移性结直肠癌：一项随机、开放标签、单中心II期临床研究（RCTS）
Public title：	Fruquintinib combined with bemozumab versus fruquintinib as third-line treatment for advanced metastatic colorectal cancer: A randomized, open-label, single-center Phase II clinical study (RCTS)
注册题目简写：
English Acronym：
研究课题的正式科学名称：	呋喹替尼联合贝莫苏拜单抗对比呋喹替尼三线治疗晚期转移性结直肠癌：一项随机、开放标签、单中心II期临床研究（RCTS）
Scientific title：	Fruquintinib combined with bemozumab versus fruquintinib as third-line treatment for advanced metastatic colorectal cancer: A randomized, open-label, single-center Phase II clinical study (RCTS)
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：	国兵	研究负责人：	戚焕鹏
Applicant：	Guo Bing	Study leader：	Qi Huanpeng
申请注册联系人电话： Applicant telephone：	+86 538 629 3598	研究负责人电话： Study leader's telephone：	+86 538 629 3585
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：	guobing967@163.com	研究负责人电子邮件： Study leader's E-mail：	hlpqtm@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：	中国山东省泰安市泰山区龙潭路29号	研究负责人通讯地址：	中国山东省泰安市泰山区龙潭路29号
Applicant address：	29 Longtan Road, Taishan District, Tai 'an, Shandong, China	Study leader's address：	29 Longtan Road, Taishan District, Tai 'an, Shandong, 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：	泰安市中心医院
Applicant's institution：	Taian Central Hospital
研究负责人所在单位：	泰安市中心医院
Affiliation of the Leader：	Taian Central Hospital

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：	(伦)准:2025-06-62	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：	泰安市中心医院医学伦理委员会
Name of the ethic committee：	The Medical Ethics Committee of Taian Central Hospital
伦理委员会批准日期： Date of approved by ethic committee：	2025-06-23 00:00:00
伦理委员会联系人：	张浩
Contact Name of the ethic committee：	Zhang Hao
伦理委员会联系地址：	中国山东省泰安市泰山区龙潭路29号
Contact Address of the ethic committee：	29 Longtan Road, Taishan District, Tai 'an, Shandong, China
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 538 629 8525	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：

泰安市中心医院

Primary sponsor：

Taian Central Hospital

研究实施负责（组长）单位地址：

中国山东省泰安市泰山区龙潭路29号

Primary sponsor's address：

29 Longtan Road, Taishan District, Tai 'an, Shandong, 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)：	山东	市(区县)：	泰安
Country：	China	Province：	Shandong	City：	Tai'an
单位(医院)：	泰安市中心医院	具体地址：	中国山东省泰安市泰山区龙潭路29号
Institution hospital：	Taian Central Hospital	Address：	29 Longtan Road, Taishan District, Tai 'an, Shandong, China

经费或物资来源：

由课题组成员自筹经费解决

Source(s) of funding：

To be resolved by the project team members through self-raised funds

研究疾病：

结直肠癌

Target disease：

Colorectal 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：

II期临床试验

Study phase：

2

研究设计：

随机平行对照

Study design：

Parallel

研究目的：

主要目的：比较呋喹替尼联合贝莫苏拜单抗对比呋喹替尼三线治疗晚期转移性结直肠癌研究参与者的客观缓解率（ORR）。次要目的：呋喹替尼联合贝莫苏拜单抗对比呋喹替尼三线治疗晚期转移性结直肠癌研究参与者的无进展生存期（PFS）、总生存期（OS）、缓解持续时间（DOR）、疾病控制率（DCR）、及安全性（按照不良反应率评价）。探索性目的：探索潜在的可能预测疗效的生物标志物，包括但不限于肿瘤突变负荷（TMB）、微卫星稳定性、EBV、ctDNA 等。

Objectives of Study：

Primary Objective: To compare the objective response rate (ORR) of participants with advanced metastatic colorectal cancer receiving fruquintinib inination with bemarituzumab versus fruquintinib alone as third-line treatment. Secondary Objectives: To compare the progression-free survival (PFS), overalsurvival (OS), duration of response (DOR), disease control rate (DCR), and safety (evaluated by incidence of adverse events) of participants with advanced metastatic colorectal cancreceiving fruquintinib in combination with bemarituzumab versus fruquintinib alone as third-line treatment. Exploratory Objective: To explore pol biomarkers that may predict efficacy, including but not limited to tumor mutational burden (TMB), microsatellite stability, EBV,

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. Age 18-75 years, no gender restriction;
2. Histologically confirmed advanced metastatic colorectal cancer;
3. Pathologically confimed MSS/pMMR;
4. At least one measurable lesion according to RECIST v1.1 criteria;
5. Previously received >=2 lines of standard chemotherapy (including oxaplatin, irinotecan, fluoropyrimidines, or regorafenib) plus targeted therapy (such as bevacizumab or cetuxiab);
6. ECOG PS: 0-1;
7. Adequate organ function:
Hematology:
Hemoglobin >=80g/L;
Neutrophi count >=1.5×10^9/L; White blood cell count >=3.5×10^9/L;
Platelets >=100×10^tic function: Serum total bilirubin <=1.5×ULN; Alanine aminotransferase (ALT), aspartate aminotsferase (AST), and alkaline phosphatase (ALP) <=3×ULN, <=5×ULN for patients with liver metastases;
Renal function: Serucreatinine <=1.5×ULN, or creatinine clearance (CrCl) calculated by Cockcroft-Gault formula >=60 mL/min;
Cardiac function: New York Heartssociation (NYHA) class <3; Left ventricular ejection fraction >=50%.
8. Expected survival >=3 months;
9. Women of childbearing potential mused reliable contraception or have a negative pregnancy test (serum or urine) within 7 days prior to enrollment, and be willing to use appropriate contraception during the trial and months after the last administration of the trial drug. For men, must agree to use appropriate contraception during the trial and for 6 months after the last administration of the tral drug;
10. Study participants voluntarily join this study, sign the informed consent form, have good compliance, and cooperate with follow-up.

排除标准：

1. 对任何试验药物及其辅料过敏，或有严重过敏史，或为试验药物的禁忌症； 2. 有未能良好控制的心脑血管事件，如：a. NYHA 2级以上心力衰竭；b.不稳定型心绞痛；c.1年内发生过心肌梗死；d.有临床意义的室上性或室性心律失常需要治疗或干预；e.脑出血和脑梗死（无症状且不需治疗的腔隙性脑梗除外）；f.12个月内发生过严重的心脑血管事件;g.不能控制的高血压，即单药治疗后收缩压>140mmHg或舒张压>90mmHg；h.入选前6个月内有动脉血栓或深静脉血栓史，或入组前2个月内具有出血倾向证据或病史的患者，无论严重程度如何；i.入选前12个月内发生卒中事件或短暂性脑缺血发作； 3. 首次给药前2周内接受过具有抗结直肠癌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、白介素，除外为控制腹水局部使用）系统性全身治疗； 4. 有间质性肺疾病、非传染性肺炎、肺纤维化、急性肺疾病，或控制不佳的全身性疾病病史（包括但不限于糖尿病、高血压等）； 5. 有活动性免疫缺陷或自身免疫性疾病病史，包括HIV检测阳性，或患有其他获得性、先天性免疫缺陷疾病，或有器官移植史、自身免疫性疾病； 6. 严重慢性或活动性感染，需要进行全身抗菌、抗真菌或抗病毒治疗，包括结核病感染等。在筛选前≥1年曾有活动性结核感染病史的患者也应排除在外，除非可以提供证明表明已经完成适当的治疗； 7. 存在脑转移或软脑膜转移； 8. 临床显著的胸腔积液、心包积液或腹水，需要在研究药物首次给药前2周内多次进行引流; 9. 入组时存在临床可检出的第二原发恶性肿瘤，或者在过去5年内出现过其它恶性肿瘤（已充分治疗的皮肤基底细胞癌或宫颈原位癌除外）； 10. 在首次研究药物给药前≤28天进行过任何大型外科手术； 11. 既往进行过异基因干细胞移植或器官移植； 12. 目前有十二指肠溃疡、溃疡性结肠炎、肠梗阻等消化道疾病或研究者判定的可能引起消化道出血或者穿孔的其他状况；或者既往有肠穿孔、肠瘘史，而经手术治疗后未痊愈者； 13. 在研究药物首次用药前4周内（含）接种过活体疫苗；季节性注射的流感疫苗通常是灭活疫苗，因此允许使用；鼻内疫苗属于活体疫苗，所以不允许使用； 14. 经研究者判断，研究参与者有其他可能导致本研究被迫中途终止的因素，如其他的严重疾病（含心理、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，会影响到研究参与者的安全，或资料及样品的收集； 15. 当前正在参与干预性临床研究治疗，或在首次给药前4 周内接受过其他研究药物或使用过研究器械治疗； 16. 研究者认为其他不符合入组条件者。往进行过异基因干细胞移植或器官移植；

Exclusion criteria：

1. Allergy to any investigational drug or its excipients, history of severe allergy, or contraindications to estigational drug; 2. Uncontrolled cardiovascular or cerebrovascular events, such as: a. NYHA Class II or higher heart failure; b. unstable angina. myocardial infarction within 1 year; d. clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention; e. cerebral hemorrhage and rebral infarction (excluding asymptomatic lacunar infarction requiring no treatment); f. severe cardiovascular or cerebrovascular events within 12 months; g. uncontrolled hyptension, i.e., systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg after monotherapy; h. history of arteriahrombosis or deep vein thrombosis within 6 months prior to enrollment, or patients with evidence or history of bleeding tendency within 2 months prior to enrollment, regardless of ; i. history of stroke or transient ischemic attack within 12 months prior to enrollment; 3. Received systemic treatment with Traditional Chinese Medicine (TCM) or drugs with immutory effects (including thymosin, interferon, interleukin, excluding local use for controlling ascites) indicated for colorectal cancer within 2 weeks prior to thfirst dose; 4. History of interstitial lung disease, non-infectious pneumonia, pulmonary fibrosis, acute pulmonary disease, or uncontrolled systemic disease (including but not limited to dtes mellitus, hypertension); 5. History of active immunodeficiency or autoimmune disease, including positive HIV test, or suffering from other acquired or congenital immunodeficiency diseases, oory of organ transplantation or autoimmune disease; 6. Severe chronic or active infection requiring systemic antibacterial, antifungal, or antiviral treatment, including tuberculosis infection, eatients with a history of active tuberculosis infection ≥1 year prior to screening should also be excluded unless proof of completed appropriate treatment can be provided; 7. Presence of brain metastas leptomeningeal metastases; 8. Clinically significant pleural effusion, pericardial effusion, or ascites requiring multiple drainage procedures within 2 weeks to the first dose of the study drug; 9. Presence of a clinically detectable second primary malignancy at enrollment, or history of other malignancies within the past 5 years (excludintely treated basal cell carcinoma of the skin or carcinoma in situ of the cervix); 10. Underwent any major surgery <=28 days prior to the first dose of th study drug; 11. Previous allogeneic stem cell transplantation or organ transplantation; 12. Currently has gastrointestinal diseases such as duodenal ulcer, ulcerative colitis, or intestinal obstruction, or other conditions determined by the inv potentially cause gastrointestinal bleeding or perforation; or has a history of intestinal perforation or fistula that has not been cured after surgical treatment; 13. Received a live vacine within 4 weeks (inclusive) prior to the first administration of the study drug; seasonal injectable influenza vaccines are usually inactivated vaccines and are therefore permitted; intranasal vacciive vaccines and are therefore not permitted; 14. The investigator determines that the study participant has other factors that may lead to forced early termination of the study, such as other serious (including psychiatric diseases) requiring concomitant treatment, severe laboratory abnormalities, or factors such as family or social issues that may affect the safety of the study participant or the collection and samples; 15. Currently participating in an interventional clinical study, or received other investigational drugs or used investigational devices within 4 weeks prior to the first adminitration; 16. Other conditions deemed ineligible by the investigator. Has previously undergone allogeneic stem cell transplantation or organ transplantation;

研究实施时间：

Study execute time：

从 From 2025-07-01 00:00:00至 To 2027-06-30 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2026-05-01 00:00:00 至 To 2027-06-30 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：	呋喹替尼+贝莫苏拜单抗	干预措施代码：
Intervention：	Fruquintinib+bemarituzumab	Intervention code：

组别：	对照组	样本量：	20
Group：	Control group	Sample size：	20
干预措施：	呋喹替尼	干预措施代码：
Intervention：	Fruquintinib	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)：	泰安
Country：	China	Province：	Shandong	City：	Tai'an
单位(医院)：	泰安市中心医院	单位级别：	三甲
Institution hospital：	Taian Central 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：	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：	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：	缓解持续时间	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：	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：	不良事件发生率	指标类型：	次要指标
Outcome：	Incidence of adverse events	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）：

本研究的随机序列由不参与受试者招募与疗效评价的第三方统计人员使用SAS 9.4软件的PROC PLAN过程，采用区组随机法产生。随机化比例1:1。

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

The random sequence for this study was generated by a third-party statistician not involved in participant recruitment or efficacy evaluation using the PROC PLAN procedure of SAS software via block randomization. The randomization ratio was 1:1.

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：	本研究为开放标签设计，不对受试者及研究者设盲。为控制偏倚，主要研究终点（无进展生存期PFS）的影像学评估将采用盲态独立中心评审（BIRC）；数据管理员及统计分析师在数据库锁定及分析前保持盲态（组别以A/B代码标示）。
Blinding：	This study is an open-label design without blinding of subjects or investigators. To control for bias, the primary endpoint (progression-free survival, PFS) will be assessed via blinded independent central review (BIRC); data managers and statistical analysts will remain blinded prior to database lock and analysis (groups will be coded as A/B).

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）：	在论文发表后6个月内，将经过去隐私化处理的、支持本研究结论的原始数据，上传至figshare公共数据库（DOI: 10.6084/m9.figshare.1234567）。数据使用需签署数据访问协议，并承诺仅用于验证学术目的。因涉及患者隐私，包含可识别信息的原始病历资料不予共享。
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	Within 6 months of publication, the de-identified raw data supporting the conclusions of this study will be uploaded to the figshare public databse (DOI: 10.6084/m9.figshare.1234567). Data access requires signing a data access agreement and a commitment to use the data solely for academiion purposes. Raw medical records containing identifiable information will not be shared due to patient privacy concerns.
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：	数据采集： 1. 来源：本研究数据来源于本院病历系统。 2. 人员：由2名研究者（主治及以上医师）独立提取并核对，如有分歧由第三位（上级医师）裁定。 3. 工具：采用标准化电子病例记录表记录，关键变量预先设定编码规则。 4. 隐私：所有数据导出前去除姓名、身份证号等18项直接标识，仅留研究编号。数据管理： 1. 存储：数据加密存储于医院内网服务器，仅课题组成员通过个人账号+动态验证码访问。 2. 备份：采用双机热备+每周离线冷备份，确保数据不丢失。 3. 质控：每月随机抽取5%样本，与原始病历进行比对，逻辑错误率要求低于1%。 4. 保存：研究结束后，所有原始数据及文档将按医院规定保存至少10年。
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	Data Collection: 1. Source: The data for this study were derived from the hospital's medical record system. 2. Personnel: Data were independentxtracted and verified by two researchers (attending physicians or above). Any discrepancies were resolved by a third party (a senior physician). 3. Tools: Standardized electronic case report forere used for recording, with predefined coding rules for key variables. 4. Privacy: Prior to data export, 18 items of direct identifiers, including names and ID numbers, ere removed, leaving only the study identification numbers. Data Management: 1. Storage: Data are encrypted and stored on the hospital's intranet server, accessible only by project team members nal accounts and dynamic verification codes. 2. Backup: A dual-machine hot standby system is used in conjunction with weekly offline cold backups to ensure data integrity. 3. Quality Contrandom sample of 5% is selected monthly for comparison with original medical records, with a requirement that the rate of logical errors be less than 1%. 4. Retn completion of the study, all raw data and documents will be retained for at least 10 years in accordance with hospital regulations.
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：	2026-04-30 14:51:34