ChiCTR2500103704 版本V1.0 版本创建时间2025/06/04 11:09:36 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：

 ChiCTR2500103704 

最近更新日期：

Date of Last Refreshed on：

 2025-06-04 11:09:25 

注册时间：

Date of Registration：

 2025-06-04 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

卡度尼利单抗联合化疗对于初始不可手术结直肠癌的转化治疗：单臂、单中心临床研究

Public title：

Combination therapy of cabozantinib and chemotherapy for the translational treatment of initially non-surgical colorectal cancer: a single arm, single center clinical study

注册题目简写：

English Acronym：

研究课题的正式科学名称：

卡度尼利单抗联合化疗对于初始不可手术结直肠癌的转化治疗：单臂、单中心临床研究

Scientific title：

Combination therapy of cabozantinib and chemotherapy for the translational treatment of initially non-surgical colorectal cancer: a single arm, single center clinical 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：

阎皓 

研究负责人：

徐靖,阎皓 

Applicant：

Hao Yan 

Study leader：

Xu Jing, Hao Yan 

申请注册联系人电话：

Applicant telephone：

 +86 132 0760 3727

研究负责人电话：

Study leader's
telephone：

+86 132 0760 3727

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：

 sarahhao99@sina.cn

研究负责人电子邮件：

Study leader's E-mail：

 sarahhao99@sina.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：

中国天津市红桥区芥园道190号

研究负责人通讯地址：

中国天津市红桥区芥园道190号

Applicant address：

No. 190 Jieyuan Road, Hongqiao District, Tianjin, China

Study leader's address：

No. 190 Jieyuan Road, Hongqiao District, Tianjin, 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：

天津市人民医院

Applicant's institution：

Tianjin People's Hospital

研究负责人所在单位：

天津市人民医院

Affiliation of the Leader：

Tianjin People's 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：

 (2023)年快审第(C25)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：

天津市人民医院医学伦理委员会

Name of the ethic committee：

Medical Ethics Committee of Tianjin People's Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

 2023-10-12 00:00:00

伦理委员会联系人：

宋磊

Contact Name of the ethic committee：

Song Lei

伦理委员会联系地址：

中国天津市红桥区芥园道190号

Contact Address of the ethic committee：

No. 190 Jieyuan Road, Hongqiao District, Tianjin, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 156 2050 0984

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：

天津市人民医院

Primary sponsor：

Tianjin People's Hospital

研究实施负责（组长）单位地址：

中国天津市红桥区芥园道190号

Primary sponsor's address：

No. 190 Jieyuan Road, Hongqiao District, Tianjin, 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)：

天津市

市(区县)：

Country：

China

Province：

Tianjin

City：

单位(医院)：

天津市人民医院

具体地址：

中国天津市红桥区芥园道190号

Institution
hospital：

Tianjin People's Hospital

Address：

No. 190 Jieyuan Road, Hongqiao District, Tianjin, China

经费或物资来源：

无

Source(s) of funding：

None

研究疾病：

初始不可手术结直肠癌  

Target disease：

Initial non-surgical 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：

 其它 

Study phase：

N/A

研究设计：

单臂 

Study design：

Single arm 

研究目的：

评价卡度尼利单抗联合化疗对于初始不可手术结直肠癌的转化治疗的有效性和安全性。  

Objectives of Study：

Evaluation of the efficacy and safety of the combination therapy of cabozantinib and chemotherapy for the conversion therapy of initially non-surgical 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.入组前签署书面知情同意书； 2.年龄＞18岁； 3.组织或病理学确诊结直肠癌患者； 4.外科，影像，病理等科室经MDT认为有机会通过药物治疗，生物治疗，放疗等方式可转化为可切除的结直肠癌患者； 5.具有可测量的病灶（根据RECIST 1.1标准，非淋巴结病灶CT扫描长径≥10 mm，淋巴结病灶 CT 扫描短径≥15 mm）； 6.ECOG PS 评分：0～1； 7.预期生存期大于 12 周； 8.重要器官的功能符合下列要求（不包括 14 天内用任何血液成分及细胞生长因子）： 1)血常规： 中性粒细胞≥1.5×109/L 血小板计数≥100×109/L 血红蛋白≥ 90g/L； 2)肝肾功能： 血清肌酐(SCr) ≤ 1.5倍正常值上限（ULN）或肌酐清除率≥50 ml/min（Cockcroft-Gault公式）； 肝功能：无肝转移受试者天门冬氨酸氨基转移酶（AST）≤2.5 x ULN，丙氨酸肝氨基转移酶（ALT）≤2.5 x ULN；肝转移受试者其ALT和AST<5 x ULN；血清总胆红素（TBIL）≤1.5 x ULN (除外Gilbert 综合征总胆红素< 3.0 mg/dL) ； 尿蛋白<2+；如果尿蛋白≥2+，则24小时尿蛋白定量显示蛋白质必须≤1g； 9.凝血功能正常，无活动性出血和血栓形成疾病 1)国际标准化比值INR≤1.5×ULN； 2)部分凝血活酶时间APTT≤1.5×ULN； 3)凝血酶原时间PT≤1.5×ULN； 10.非手术绝育或育龄期女性患者，需要在研究治疗期间和研究治疗期结束后3个月内采用一种经医学认可的避孕措施（如宫内节育器，避孕药或避孕套）；非手术绝育的育龄期女性患者在研究入组前的7 天内血清或尿HCG检查必须为阴性；而且必须为非哺乳期。 11.受试者自愿加入本研究，依从性好，配合安全性和生存期随访。

Inclusion criteria

1. Sign a written informed consent form before joining the group; 2. Age>18 years old; 3. Patients diagnosed with colorectal cancer through organization or pathology; 4. According to MDT, departments such as surgery, imaging, pathology, etc. have the opportunity to transform patients with resectable colorectal cancer through drug therapy, biological therapy, radiotherapy, and other methods; 5. Have measurable lesions (according to RECIST 1.1 standards, non lymph node lesions have a CT scan length of >= 10 mm, and lymph node lesions have a CT scan length of >= 15 mm); 6. ECOG PS score: 0 to 1; 7. Expected survival period greater than 12 weeks; 8. The function of important organs meets the following requirements (excluding the use of any blood components and cell growth factors within 14 days): (1) Blood routine: Neutrophils >= 1.5 × 10^9/L Platelet count >= 100 × 10^9/L Hemoglobin >= 90g/L; (2) Liver and kidney function: Serum creatinine (SCr) <= 1.5 times the upper limit of normal (ULN) or creatinine clearance rate >= 50 ml/min (Cockcroft Gault formula); Liver function: In subjects without liver metastasis, aspartate aminotransferase (AST) <= 2.5 x ULN and alanine aminotransferase (ALT) <= 2.5 x ULN; ALT and AST<5 x ULN in subjects with liver metastasis; Serum total bilirubin (TBIL) <= 1.5 x ULN (excluding Gilbert syndrome total bilirubin<3.0 mg/dL); Urinary protein<2+; If urine protein is >= 2+, the 24-hour urine protein quantification must show protein <= 1g; 9. Normal coagulation function, no active bleeding or thrombotic diseases (1) International Standardization Ratio INR <= 1.5 × ULN; (2) Partial thromboplastin time APTT <= 1.5 × ULN; (3) Prothrombin time PT <= 1.5 × ULN; 10. Non surgical sterilization or female patients of childbearing age are required to use a medically approved contraceptive measure (such as intrauterine device, contraceptive pill, or condom) during the study treatment period and within 3 months after the end of the study treatment period; Female patients of childbearing age who undergo non-surgical sterilization must have a negative serum or urine HCG test within 7 days prior to enrollment in the study; And it must be non lactating. 11. The subjects voluntarily joined this study, had good compliance, and cooperated with safety and survival follow-up.

排除标准：

具有以下任何一项的患者不能入组本研究： 1.受试者既往或同时患有其它恶性肿瘤（已治愈的皮肤基底细胞癌和宫颈原位癌除外）； 2.已知受试者既往对大分子蛋白制剂，或已知对应用的药物成分过敏； 3.受试者存在任何活动性自身免疫病或有自身免疫病病史（如以下，但不局限于：自身免疫性肝炎、间质性肺炎，葡萄膜炎，肠炎，肝炎，垂体炎，血管炎，肾炎，甲状腺功能亢进，甲状腺功能降低，既往曾接受过甲状腺手术者不能纳入；受试者患有白癜风或在童年期哮喘已完全缓解，成人后无需任何干预的可纳入；受试者需要支气管扩张剂进行医学干预的哮喘则不能纳入）； 4.受试者正在使用免疫抑制剂、或全身、或可吸收的局部激素治疗以达到免疫抑制目的（剂量>10mg/天泼尼松或其他等疗效激素），并在入组前2周内仍在继续使用的； 5.有临床症状的腹水或胸腔积液，需要治疗性的穿刺或引流； 6.有未能良好控制的心脏临床症状或疾病，如：（1）NYHA2级以上心力衰竭（2）不稳定型心绞痛（3）1年内发生过心肌梗死（4）有临床意义的室上性或室性心律失常需要治疗或干预的患者； 7.受试者有活动性感染或在筛选期间、首次给药前发生原因不明发热>38.5度（经研究者判断，受试者因肿瘤产生的发热可以入组）； 8.既往和目前有肺纤维化史、间质性肺炎、尘肺、放射性肺炎、药物相关肺炎、肺功能严重受损等的客观证据的患者； 9.受试者先天或后天免疫功能缺陷，如HIV感染者，或活动性肝炎（转氨酶不符合入选标准，乙肝参考：HBV DNA≥1000 IU/ml；丙肝参考： HCV RNA≥1000 IU/ml）；慢性乙型肝炎病毒携带者，HBV DNA＜2000 IU/ml，试验期间必须同时接受抗病毒治疗才可以入组； 10.研究用药前不足4周内或可能于研究期间接种活疫苗； 11.受试者已知有精神类药物滥用、酗酒或吸毒史； 12.首次给药前2周内曾接受具有抗肿瘤适应症的中草药或中成药 。 13.研究者认为应排除在本研究之外，例如经研究者判断，受试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，会影响到受试者的安全，或资料及样品的收集。

Exclusion criteria：

Patients with any of the following conditions are not eligible for inclusion in this study: 1. The subject has previous or concurrent malignant tumors (excluding cured skin basal cell carcinoma and cervical carcinoma in situ); 2. It is known that the subject has a history of allergies to large molecule protein preparations or to the drug ingredients used; 3. Subjects with any active autoimmune diseases or a history of autoimmune diseases (such as but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism, those who have undergone thyroid surgery in the past cannot be included; subjects with vitiligo or complete remission of childhood asthma without any intervention in adulthood can be included; subjects with asthma requiring bronchodilators for medical intervention cannot be included); 4. The subject is currently using immunosuppressants, systemic, or absorbable local hormone therapy to achieve immunosuppression (dose>10mg/day prednisone or other therapeutic hormones), and has continued to use it within 2 weeks before enrollment; 5. Ascites or pleural effusion with clinical symptoms require therapeutic puncture or drainage; 6. Patients with uncontrolled clinical symptoms or diseases of the heart, such as: (1) NYHA grade 2 or above heart failure, (2) unstable angina pectoris, (3) myocardial infarction within 1 year, and (4) clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention; 7. If the subject has an active infection or an unexplained fever>38.5 degrees Celsius during the screening period or before the first administration (according to the researcher's judgment, the subject can be included if the fever is caused by the tumor); 8. Patients with objective evidence of past and current history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, severe impairment of lung function, etc; 9. Subjects with congenital or acquired immune deficiency, such as HIV infected persons, or active hepatitis (transaminase does not meet the inclusion criteria, hepatitis B reference: HBV DNA >= 1000 IU/ml; Hepatitis C reference: HCV RNA >= 1000 IU/ml); Chronic carriers of hepatitis B virus, HBV DNA<2000 IU/ml, During the trial period, antiviral treatment must be received simultaneously in order to be enrolled; 10. Within 4 weeks prior to the study medication, or possibly during the study period, receiving a live vaccine; 11. The subject is known to have a history of substance abuse, alcoholism, or drug use; 12. Accepted Chinese herbal medicine or traditional Chinese patent medicines and simple preparations with anti-tumor indications within 2 weeks before the first administration. 13.The researchers believe that the subjects should be excluded from this study, for example, if the researchers determine that there are other factors that may cause the study to be terminated midway, such as other serious illnesses (including mental illnesses) that require concomitant treatment, serious laboratory abnormalities, accompanied by family or social factors, which may affect the safety of the subjects, or the collection of data and samples.

研究实施时间：

Study execute time：

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

征募观察对象时间：

Recruiting time：

从 From 2023-11-29 00:00:00 至 To 2025-10-12 00:00:00

干预措施：

Interventions：

组别：

卡度尼利单抗联合化疗组

样本量：

 20

Group：

Cadonilimab combined with chemotherapy group

Sample size：

干预措施：

术前转化治疗，每2周一个治疗周期，2-4周期。分别进行以下治疗：卡度尼利单抗，6 mg/kg, iv, Q2W；FOLFOX, Q2W；术后辅助治疗：卡度尼利单抗，6 mg/kg, iv, Q2W，用至一年。

干预措施代码：

Intervention：

Preoperative conversion therapy, with a treatment cycle of 2-4 cycles every 2 weeks. Perform the following treatments separately: Cardolizumab, 6 mg/kg, iv, Q2W; FOLFOX, Q2W; Postoperative adjuvant therapy: Cardolizumab, 6 mg/kg, iv, Q2W, Used for one year.

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 天津市 

市(区县)：

  

Country：

China

Province：

Tianjin

City：

单位(医院)：

 天津市人民医院 

单位级别：

 三甲 

Institution
hospital：

Tianjin People's Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

转化切除率

指标类型：

主要指标

Outcome：

Conversion resection rate

Type：

Primary 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：

正在进行

Recruiting

年龄范围：

Participant age：
最小 Min age 18 岁 years
最大 Max age 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）：

2025-10-11 sarahhao99@sina.cn

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

2025-10-11 sarahhao99@sina.cn

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：

  2025-06-04 11:09:25