ChiCTR2300076973 版本V1.0 版本创建时间2023/10/25 16:17:30 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：

 ChiCTR2300076973 

最近更新日期：

Date of Last Refreshed on：

 2023-10-25 16:17:24 

注册时间：

Date of Registration：

 2023-10-25 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

阿得贝利单抗联合苹果酸法米替尼和化疗二线治疗转移性结直肠癌

Public title：

Adbelimumab plus famitinib malate and chemotherapy as second-line treatment for metastatic colorectal cancer

注册题目简写：

English Acronym：

研究课题的正式科学名称：

阿得贝利单抗联合苹果酸法米替尼和化疗二线治疗转移性结直肠癌： 一项开放标签、单中心、单臂研究

Scientific title：

Adbelimumab plus famitinib malate and chemotherapy as second-line treatment for metastatic colorectal cancer: an open-label, single-center, single-arm study

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：

刁俊伟 

研究负责人：

何义富 

Applicant：

Diao Junwei 

Study leader：

He Yifu 

申请注册联系人电话：

Applicant telephone：

 +86 158 5065 7500

研究负责人电话：

Study leader's
telephone：

+86 189 6378 9042

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：

 15850657500@163.com

研究负责人电子邮件：

Study leader's E-mail：

 834638033@qq.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：

江苏省南京市鼓楼区中央路19号

研究负责人通讯地址：

安徽省合肥市庐阳区庐江路17号中国科学技术大学附属第一医院西区(安徽省肿瘤医院)

Applicant address：

19 zhongyang road, gulou district, nanjing city of jiangsu province

Study leader's address：

Anhui Provincial Hospital,17 Lujiang Road, Luyang District, Hefei City, Anhui Province

申请注册联系人邮政编码：

Applicant postcode：

 230001

研究负责人邮政编码：

Study leader's postcode：

 230001

申请人所在单位：

江苏恒瑞医药股份有限公司

Applicant's institution：

Jiangsu Hengrui Pharmaceutical Co., Ltd

研究负责人所在单位：

安徽省肿瘤医院

Affiliation of the Leader：

Anhui Provincial 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：

 伦审2023第70号

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：

安徽省肿瘤医院医学伦理委员会

Name of the ethic committee：

Institutional research ethics committee of Anhui Provincial Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

 2023-08-07 00:00:00

伦理委员会联系人：

钱立庭

Contact Name of the ethic committee：

Qian Liting

伦理委员会联系地址：

合肥市蜀山区环湖东路 107号

Contact Address of the ethic committee：

107 Huanhu East Road, Shushan District, Hefei City

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 551 6532 7725

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：

安徽省肿瘤医院

Primary sponsor：

Anhui Provincial Cancer Hospital

研究实施负责（组长）单位地址：

安徽省合肥市庐阳区庐江路17号，中国科学技术大学附属第一医院西区(安徽省肿瘤医院)

Primary sponsor's address：

Anhui Provincial Hospital,17 Lujiang Road, Luyang District, Hefei City, Anhui Province

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

安徽省

市(区县)：

Country：

China

Province：

Anhui Province

City：

单位(医院)：

安徽省肿瘤医院

具体地址：

安徽省合肥市庐阳区庐江路17号

Institution
hospital：

Anhui Provincial Cancer Hospital

Address：

17 Lujiang Road, Luyang District, Hefei Cit

经费或物资来源：

自募

Source(s) of funding：

Self recruitment

研究疾病：

转移性结直肠癌  

Target disease：

metastatic 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：

 I期+II期 

Study phase：

1-2

研究设计：

单臂 

Study design：

Single arm 

研究目的：

主要目的：评价阿得贝利单抗联合苹果酸法米替尼和化疗二线用于转移性结直肠癌的疗效及安全性  

Objectives of Study：

Main purpose: To evaluate the efficacy and safety of adbelimumab combined with famitinib malate and chemotherapy in the second-line treatment of metastatic colorectal cancer

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.≥18岁，性别不限； 2.经病理学确诊的转移性结、直肠腺癌（所有其他组织学类型都排除在外）受试者； 3.既往曾接受过一线标准化疗且治疗失败。 4.根据 RECIST 1.1 标准，受试者至少具有一个可测量的靶病灶； 5.ECOG评分：0~1 分； 6.预计生存期 ≥3 个月； 7.主要器官功能良好，即入组前14天内相关检查指标满足以下要求：（1）血常规检查（筛选前14天内未输血，未用过升白、升血小板药物）：血红蛋白 > 90 g/L；中性粒细胞计数> 1.5×109/L；血小板计数> 100×109/L；（2）生化检查：总胆红素 ≤ 1.5×ULN（正常值上限）；血谷丙转氨酶（ALT）和血谷草转氨酶（AST）≤ 2×ULN；如有肝转移，则ALT和AST ≤ 5×ULN；内生肌酐清除率 ≥ 60 ml/min（Cockcroft-Gault公式）；（3）心脏多普勒超声评估：左室射血分数 (LVEF，Left ventricular ejection fraction) ≥ 50%； 8.若患有乙型肝炎病毒（HBV）感染，如 HBsAg 阳性，需检测 HBV-DNA，且HBV-DNA 需<2000 IU/mL（若研究中心只有 copy/mL 检测单位，则必须<104 copy/mL）；对于 HBV-DNA≥2000 IU/mL 的受试者，首次用药前接受至少 1 周的抗病毒治疗（仅允许使用核苷类药物如恩替卡韦、富马酸替诺福韦酯和富马酸丙酚替诺福韦片），且病毒拷贝数相比首次用药前下降 10 倍（1 lg）以上。对于 HBV 感染者，需在研究期间全程接受抗病毒治疗。丙型肝炎病毒（HCV）-RNA 阳性受试者必须按治疗指南接受抗病毒治疗； 9.育龄妇女在首次用药前 3 天内必须妊娠检测为（βHCG）阴性。育龄妇女和男子(与育龄妇女发生性关系)必须同意在治疗期间和末次给药后 6 个月内避孕；

Inclusion criteria

1. ≥18 years of age, gender not limited; 2. Subjects with pathologically confirmed metastatic colorectal adenocarcinoma (all other histological types excluded); 3. Prior failure of first-line standard chemotherapy. 4. Subject had at least one measurable target lesion according to RECIST 1.1 criteria; 5. ECOG score: 0 ~ 1; 6. The expected survival period for 3 months or more; 7. Good main organ function, that is, the relevant examination indicators within 14 days before enrollment meet the following requirements: (1) blood routine examination (no blood transfusion, no use of white blood cell and platelet raising drugs within 14 days before screening) : hemoglobin > 90 g/L; Neutrophil count > 1.5×109/L; The platelet count > 100 x 109 / L; (2) Biochemical examination: total bilirubin ≤ 1.5×ULN (upper limit of normal value); Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2×ULN; If there was liver metastasis, ALT and AST ≤ 5×ULN; The endogenous creatinine clearance or 60 ml/min (Cockcroft - Gault formula); (3) Echocardiography: Left ventricular ejection fraction (LVEF) ≥ 50%; 8. If you have hepatitis B virus (HBV) infection, if HBsAg is positive, HBV-DNA should be tested, and HBV-DNA should be <2000 IU/mL (<104 copy/mL if the research center has only copy/mL testing unit); Participants with HBV-DNA≥2000 IU/mL received antiviral therapy (only nucleoside drugs such as entecavir, tenofovir dipivoxil fumarate, and tenofovir propofol fumarate tablets) for at least 1 week before the first dose and had a viral copy number decrease of more than 10-fold (1 lg) from the baseline. For HBV infection, need to accept the antiviral treatment during the whole research. Hepatitis C virus (HCV) -RNA positive subjects must receive antiviral therapy according to treatment guidelines. 9. Women of childbearing age must be within three days of pregnancy in the first drug testing for (beta HCG) negative. Women of reproductive age and men (who have sex with a woman of reproductive age) must agree to contraception during treatment and for 6 months after the last dose;

排除标准：

1.以往或同时患有其它恶性肿瘤，但是已治愈的皮肤基底细胞癌和宫颈原位癌除外； 2.既往接受过VEGFR类小分子酪氨酸激酶抑制剂（如法米替尼、索拉非尼、舒尼替尼、瑞戈非尼等）治疗的受试者； 3.既往接受过 ICS（如PD-1/PD-L1抑制剂、CTLA-4抑制剂）治疗的受试者； 4.四周内参加过其他药物临床试验； 5.接受其它治疗造成的损害未恢复者，其中接受亚硝基或丝裂霉素的间隔距服用研究药物 ≥6周；接受其它细胞毒性药物、靶向药物、放疗或手术 ≥4周，且伤口已完全愈合；接受中成药或中药 ≥2周； 6.具有影响口服药物的多种因素（比如无法吞咽、慢性腹泻和肠梗阻等）； 7.有出血病史，筛选前4周内发生任何严重分级达到 CTCAE 5.0中 3 度或以上的出血事件； 8.筛选前已知有中枢神经系统转移或有中枢神经系统转移病史的受试者。对于临床疑似中枢神经系统转移的受试者，入组前28天内必须进行增强CT或增强核磁共振（MRI，Magnetic Resonance Imaging）检查，排除中枢神经系统转移； 9.患有高血压且经单一降压药物治疗无法获得良好控制者（收缩压 > 140 mmHg，舒张压 > 90 mmHg）；具有不稳定型心绞痛病史者；筛选前3个月内新诊断为心绞痛者或筛选前6个月内发生心肌梗塞事件；心律失常（包括QTcF： 男性 ≥ 450 ms，女性 ≥ 470 ms）需长期使用抗心律失常药物及纽约心脏病协会分级 ≥ II级心功能不全； 10.尿常规提示尿蛋白 ≥ ++ 且证实24小时尿蛋白定量 >1.0 g； 11.患有活动性感染、首次用药前7天内有不明原因发热≥ 38.5℃、或基线期白细胞计数 > 15×109/L； 12.既往或目前有间质性肺炎/间质性肺病、需接受糖皮质激素系统治疗的肺炎；目前有活动性肺炎或肺功能检查证实肺功能重度受损者； 13.长期未愈合的伤口或愈合不全的骨折； 14.影像学显示肿瘤已侵犯重要血管周或经研究者判断受试者肿瘤在治疗期间有极高可能侵袭重要血管而引起致命大出血的情况； 15.凝血功能异常，具有出血倾向者（入组前14天必须满足：在不使用抗凝剂的情况下INR在正常值范围内）；应用抗凝剂或维生素K 拮抗剂如华法林、肝素或其类似物治疗的受试者；在凝血酶原时间国际标准化比值（INR，International Normalized Ratio）≤ 1.5的前提下，允许以预防目的使用小剂量华法林（1 mg口服，每日一次）或小剂量阿司匹林（每日用量不超过100 mg）； 16.筛选前一年内发生过动/静脉血栓事件，如脑血管意外（包括暂时性缺血性发作）、深静脉血栓（因前期化疗行静脉置管引发静脉血栓经研究者判断已痊愈者除外）及肺栓塞等； 17.既往存在甲状腺功能异常，即使在药物治疗的情况下，甲状腺功能仍不能维持在正常范围内； 18.具有精神类药物滥用史且无法戒除者或有精神障碍的； 19.有临床症状，需要临床干预或稳定时间小于4周的浆膜腔积液（如胸腔积液、心包积液和腹水）； 20.有免疫缺陷病史，或患有其它获得性、先天性免疫缺陷疾病，或有器官移植史； 21.根据研究者的判断，有严重的危害受试者安全或影响受试者完成研究的伴随疾病。

Exclusion criteria：

1. In the past or at the same time with other malignant tumours, but has been cured except skin basal cell carcinoma and cervical carcinoma in situ; 2. Always received VEGFR class small molecule tyrosine kinase inhibitors (e.g., rice for Nepal, sorafenib, chougny, rui GeFei, etc.) for treatment of the subjects; 3. Subjects previously treated with ICS (e.g., PD-1/PD-L1 inhibitors, CTLA-4 inhibitors); 4. Participated in other drug clinical trials within four weeks; 5. Patients who have not recovered from other treatments, in which the interval between receiving nitroso or mitomycin and taking the study drug was 6 weeks or more; Received other cytotoxic drugs, targeted drugs, radiotherapy or surgery for more than 4 weeks, and the wound has been completely healed. Receiving Chinese patent medicine or Chinese medicine for ≥2 weeks; 6. Multiple factors affecting oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction); 7. Patients with a history of bleeding, with any bleeding event of CTCAE 5.0 grade 3 or higher within 4 weeks before screening; 8. Subjects with known CNS metastases prior to screening or a history of CNS metastases were screened. Subjects with clinically suspected central nervous system metastases had to undergo contrast-enhanced CT or Magnetic Resonance Imaging (MRI) within 28 days before enrollment to exclude central nervous system metastases. 9. Patients with hypertension not well controlled by single antihypertensive medication (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg); Patients with a history of unstable angina; 3 months prior to screening new diagnosis of angina pectoris or myocardial infarction incident within 6 months prior to screening; Arrhythmias (including QTcF ≥ 450 ms in men and ≥ 470 ms in women) required long-term use of antiarrhythmic drugs and New York Heart Association (NYHA) grade ≥ II cardiac dysfunction. 10. Urine routine showed urine protein ≥ ++ and confirmed 24-hour urine protein quantitation >1.0 g; 11. Active infection, fever of unknown origin ≥ 38.5℃ within 7 days before the first dose, or white blood cell count > 15×109/L at baseline; 12. Previous or current interstitial pneumonia/interstitial lung disease requiring systemic glucocorticoid therapy; There are currently active pneumonia or pulmonary function tests confirmed severely impaired lung function; 13. Not for a long time to heal the wounds or incomplete healing of fracture. 14. Imaging shows that the tumor has invaded the important blood vessels or the investigator judges that the subject's tumor has a high probability of invading the important blood vessels during the treatment and causing fatal hemorrhage; 15. Patients with abnormal coagulation function and bleeding tendency (INR within the normal range without using anticoagulants must be met within 14 days before enrollment); Subjects treated with anticoagulants or vitamin K antagonists such as warfarin, heparin, or their analogues; Low-dose warfarin (1 mg orally once daily) or low-dose aspirin (at a dose of up to 100 mg daily) for preventive purposes were allowed if the International Normalized Ratio of prothrombin time (INR) was 1.5 or less. 16. Arterial/venous thrombosis events occurred within one year before screening, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis (except for venous thrombosis caused by venous catheterization due to previous chemotherapy and judged by investigators to be cured), pulmonary embolism, etc. 17. Had abnormal thyroid function in the past, and the thyroid function could not be maintained in the normal range even in the case of drug treatment; 18. A history of psychiatric drugs abuse and can't quit or have a mental disorder; 19 patients with clinical symptoms, clinical intervention or stable time less than 4 weeks of serous cavity effusion (such as pleural effusion and pericardial effusion and ascites); 20. A history of immunodeficiency or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; 21. According to the investigator's judgment, there are concomitant diseases that seriously endanger the safety of the subject or prevent the subject from completing the study.

研究实施时间：

Study execute time：

从 From 2023-10-26 00:00:00至 To 2026-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2023-10-26 00:00:00 至 To 2025-12-01 00:00:00

干预措施：

Interventions：

组别：

试验组

样本量：

 44

Group：

experimental group

Sample size：

干预措施：

阿得贝利单抗+苹果酸法米替尼+化疗

干预措施代码：

Intervention：

Adbelimumab+famitinib malate+chemotherapy

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 安徽省 

市(区县)：

  

Country：

China

Province：

Anhui Province

City：

单位(医院)：

 安徽省立医院 

单位级别：

 三级甲等 

Institution
hospital：

Anhui Provincial 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：

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：

总生存时间

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：

无进展生存期

指标类型：

次要指标

Outcome：

Progressives free 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：

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 99 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

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)：

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：

病例记录表

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：

暂未确定/Not yet

注册人：

Name of Registration：

  2023-10-25 16:17:24