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：	ChiCTR2500100304
最近更新日期： Date of Last Refreshed on：	2025-04-07 17:47:21
注册时间： Date of Registration：	2025-04-07 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	盐酸安罗替尼胶囊联合131I治疗远处转移性分化型甲状腺癌的单臂、开放、多中心临床研究
Public title：	A single-arm, open, multicenter clinical study of anrotinib capsule combined with 131I in the treatment of distant metastatic differentiated thyroid cancer
注册题目简写：
English Acronym：
研究课题的正式科学名称：	盐酸安罗替尼胶囊联合131I治疗远处转移性分化型甲状腺癌的单臂、开放、多中心临床研究
Scientific title：	A single-arm, open, multicenter clinical study of anrotinib capsule combined with 131I in the treatment of distant metastatic differentiated thyroid cancer
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：	郑薇	研究负责人：	郑薇
Applicant：	Wei Zheng	Study leader：	Wei Zheng
申请注册联系人电话： Applicant telephone：	+86 139 2083 1158	研究负责人电话： Study leader's telephone：	+86 139 2083 1158
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：	zhengw@tmu.edu.cn	研究负责人电子邮件： Study leader's E-mail：	zhengw@tmu.edu.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：	天津市和平区鞍山道154号	研究负责人通讯地址：	天津市和平区鞍山道154号
Applicant address：	154 Anshan Road, Heping District, Tianjin, China	Study leader's address：	154 Anshan Road, Heping 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：	天津医科大学总医院
Applicant's institution：	Tianjin Medical University General Hospital
研究负责人所在单位：	天津医科大学总医院
Affiliation of the Leader：	Tianjin Medical University General 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：	IRB2024-YX-524-01	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：	天津医科大学总医院医学伦理委员会
Name of the ethic committee：	Medical Ethics Committee of Tianjin Medical University General Hospital
伦理委员会批准日期： Date of approved by ethic committee：	2024-11-28 00:00:00
伦理委员会联系人：	金冬来
Contact Name of the ethic committee：	Donglai Jin
伦理委员会联系地址：	天津市和平区鞍山道154号
Contact Address of the ethic committee：	154 Anshan Road, Heping District, Tianjin, China
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 22 6036 1044	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：

天津医科大学总医院

Primary sponsor：

Tianjin Medical University General Hospital

研究实施负责（组长）单位地址：

天津市和平区鞍山道154号

Primary sponsor's address：

154 Anshan Road, Heping 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(区县)：
Country：	China	Province：	Tianjin	City：
单位(医院)：	天津医科大学总医院	具体地址：	天津市和平区鞍山道154号
Institution hospital：	Tianjin Medical University General Hospital	Address：	154 Anshan Road, Heping District, Tianjin, China

经费或物资来源：

公司赞助

Source(s) of funding：

Corporate sponsorship

研究疾病：

甲状腺癌

Target disease：

Thyroid 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：

非随机对照试验

Study design：

Non randomized control

研究目的：

评价安罗替尼联合131I治疗远处转移性分化型甲状腺癌的疗效与安全性。

Objectives of Study：

To evaluate the efficacy and safety of anlotinib combined with 131I in the treatment of distant metastatic differentiated thyroid 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：

Inclusion criteria

1. Age 18-75 years old;
2. ECOG PS score: 0~1; Expected survival of more than 3 months;
3. Patients voluntarily participated in this study and signed informed consent;
4. Distant metastatic differentiated thyroid cancer was confirmed by histopathology or imaging, and the patient had at least one measurable (according to RECIST1.1) metastatic lesion (such as lung, bone, brain and other distant metastases) after total or subtotal thyroidectomy.
5. Plan to receive RAI treatment, and whole-body imaging after RAI treatment confirms the presence of at least one iodine-capable metastasis;
6. Major organ functions within 7 days prior to treatment meet the following criteria:
(1) Blood routine examination criteria (without blood transfusion within 14 days) :
1) Hemoglobin (HB) >= 90g/L
2) Neutrophil absolute value (ANC) >= 1.5×10^9/L
3) Platelet (PLT)  >= 80×10^9/L
(2) Biochemical examination shall meet the following standards:
1) Total bilirubin (TBIL) <= 1.5 times the upper limit of normal (ULN)
2) Alanine aminotransferase (ALT) and aspartate aminotransferase AST <=2.5ULN
3) Serum creatinine (Cr) <= 1.5ULN and creatinine clearance (CCr) >= 60ml/min;
(3) Urine protein < 2+ by routine urine test;
(4) Good coagulation function, PT<=1.5×ULN;
(5) Cardiac ultrasound: left ventricular ejection fraction (LVEF) >= (50%)
7. A woman of reproductive age (e.g., a woman who has not undergone surgical sterilization or less than 1 year after menopause) has a negative blood pregnancy test and must be a non-lactating patient; Men and women of childbearing age agree that they must use effective contraception from the beginning of the informed consent and for six months after the end of the study, and must not donate sperm or eggs.

排除标准：

出现以下任一项目的患者将不能入组本研究： 1.＜18岁的儿童及青少年。 2.经组织病理学或影像学确诊的未分化型甲状腺癌或髓样甲状腺癌。 3.既往使用过任何小分子TKI，如安罗替尼、凡德他尼（Vandetanib）、卡博替尼（Cabozantinib）、仑伐替尼、舒尼替尼、索拉非尼、贝伐珠单抗等进行抗肿瘤治疗的患者。使用过RET抑制剂如LOXO-292，Blu-667的患者。 4.近3个月内接受过其他抗肿瘤局部治疗，或在本次研究用药期间计划进行全身抗肿瘤治疗或外照射或其他介入治疗，包括细胞毒疗法、信号转导抑制剂、免疫疗法 (或在接受试验药物治疗前6周内使用过丝裂霉素C)。使用左甲状腺素进行TSH抑制及甲状腺素补充治疗不在禁止之列。研究期间不可同时使用中药抗肿瘤治疗。 5.5年内出现过或当前同时患有其它恶性肿瘤，治愈的子宫颈原位癌、非黑色素瘤的皮肤癌和表浅的膀胱肿瘤除外 [Ta (非浸润性肿瘤)，Tis (原位癌) 和T1 (肿瘤浸润基膜)] 或实体器官、骨髓移植患者。 6.由于任何既往治疗引起的高于CTC AE(5.0) 1 级以上的未缓解的毒性反应，不包括脱发。 7.具有影响口服药物的多种因素（比如无法吞咽）者。 8.伴胸腔积液或腹水，引起呼吸道综合征(≥CTC AE 2级呼吸困难[2级呼吸困难指少量活动时呼吸短促；影响工具性日常生活活动])。 9.存在任何重度和/或未能控制的疾病的患者，包括：（1）患有高血压且经2种降压药物治疗血压仍控制不理想（收缩压≥150 mmHg，舒张压≥100 mmHg）患者；（2）显著的心血管损害包括但不限于：≥Ⅱ级充血性心功能衰竭（纽约心脏病协会（NYHA）分级) ，不稳定型心绞痛，心肌梗死，缺血性心肌病或首次服药前6个月内发生过脑卒中（3）1级以上窦性心动过缓（CTCAE 5.0）；或二度以上房室传导阻滞，或窦性停搏（已安装起搏器的除外）；心律失常（包括QTC ≥480ms）；需要同时使用已知可以延长QTc间期药物，包括抗心律失常治疗者；（4）活动性或未能控制的严重感染(≥CTC AE 2级感染)；（5）肝硬化、失代偿性肝病，活动性肝炎或慢性肝炎的患者；（6）肾功能衰竭需要血液透析或腹膜透析；（7）有免疫缺陷病史，包括HIV阳性或患有其它获得性、先天性免疫缺陷疾病，或有器官移植史者；（8）糖尿病患者血糖控制不佳（空腹血糖（FBG）＞10mmol/L）；（9）尿常规提示尿蛋白≥2+，且证实24小时尿蛋白定量＞1.0 g者。 10.分组前 28 天内接受了重大外科治疗、切开活检或明显创伤性损伤。 11.影像学显示肿瘤已侵犯重要血管周或经研究者判断在后续研究期间肿瘤极有可能侵袭重要血管而引起致命大出血的患者。 12.不管严重程度如何，存在任何出血体质迹象或病史的患者；在分组前4周内，出现任何出血或流血事件≥CTCAE 2级的患者，存在未愈合创口、溃疡或骨折。 13.6个月内发生过动/静脉血栓事件，如脑血管意外（包括暂时性缺血性发作）、深静脉血栓及肺栓塞者。 14.有动脉瘤病史且存在破裂可能。 15.有癫痫病史或有共济失调的神经系统疾病需要治疗的。 16.具有精神类药物滥用史且无法戒除或有精神障碍者。 17.有周围神经系统疾病病史，肌力在3级以下者。 18.四周内参加过其他抗肿瘤药物临床试验或正在进行其他临床试验者。 19.根据研究者的判断，有严重危害患者安全或影响患者完成研究的伴随疾病者。

Exclusion criteria：

Patients with any of the following conditions will not be enrolled in this study: 1. Children and adolescents under 18 years of age. 2. Undifferentiated thyroid carcinoma or medullary thyroid carcinoma confirmed by histopathology or imaging. 3. Patients who have previously used any small molecule TKI for anti-tumor therapy, such as antirotinib, Vandetanib, Cabozantinib, Renvastinib, Sunitinib, sorafenib, bevacizumab, etc. Patients who have used RET inhibitors such as LOXO-292, Blu-667. 4. Received other local antitumor therapy within the last 3 months, or planned systemic antitumor therapy or external irradiation or other interventional therapy during the duration of this study, including cytotoxic therapy, signal transduction inhibitors, immunotherapy (or mitomycin C within 6 weeks prior to receiving the trial drug). TSH inhibition and thyroxine supplementation with levothyroxine are not prohibited. During the study period, Chinese herbal antitumor therapy should not be used simultaneously. 5.Patients who have had or are currently having other malignancies within 5.5 years, except cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors [Ta (non-invasive tumor), Tis (cancer in situ), and T1 (tumor infiltrating basal membrane)] or solid organ or bone marrow transplantation. 6. Unmitigated toxic effects above CTC AE(5.0) grade 1 due to any previous treatment, excluding hair loss. 7. People who have multiple factors affecting oral medication (such as inability to swallow). 8. Accompanied by pleural effusion or ascites, respiratory syndrome (>=CTC AE grade 2 dyspnea [Grade 2 dyspnea refers to shortness of breath with a small amount of activity; affecting instrumental activities of daily living]). 9. Patients with any severe and/or uncontrolled disease, including: (1) Patients with hypertension who still have unsatisfactory blood pressure control after treatment with 2 antihypertensive drugs (systolic blood pressure ≥150 mmHg, diastolic blood pressure >=100 mmHg); (2) Significant cardiovascular impairment includes, but is not limited to: ≥ Grade II congestive heart failure (New York Heart Association (NYHA) classification), unstable angina, myocardial infarction, ischemic cardiomyopathy, or stroke within 6 months before first medication (3) Sinus bradycardia of grade 1 and above (CTCAE 5.0); Or more than a second degree of atrioventricular block, or sinus arrest (except when a pacemaker is installed); Arrhythmia (including QTC >=480ms); The need for concurrent use of drugs known to prolong the QTc interval, including antiarrhythmic therapies; (4) Active or uncontrolled severe infection (>=CTC AE grade 2 infection); (5) Patients with cirrhosis, decompensated liver disease, active hepatitis or chronic hepatitis; (6) Renal failure requires hemodialysis or peritoneal dialysis; (7) A history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; (8) Poor blood glucose control in diabetic patients (fasting blood glucose (FBG) > 10mmol/L); (9) Urine routine indicated urine protein >=2+, and confirmed 24-hour urine protein quantity > 1.0 g. 10. Major surgical treatment, open biopsy, or significant traumatic injury were received within 28 days prior to grouping. 11. Patients whose imaging shows that the tumor has invaded important blood vessels or who are judged by the investigators to be highly likely to invade important blood vessels and cause fatal major bleeding during follow-up studies. 12. Patients with any physical signs or history of bleeding, regardless of severity; Non-healing wounds, ulcers, or fractures were present in patients with any bleeding or bleeding events >=CTCAE grade 2 during the 4 weeks prior to grouping. 13.6 months after the occurrence of arterial/venous thrombosis events, such as cerebrovascular accidents (including temporary ischemic attacks), deep vein thrombosis and pulmonary embolism. 14. Have a history of aneurysms with the possibility of rupture. 15. Have a history of epilepsy or have ataxia neurological disease that requires treatment. 16. People who have a history of psychotropic drug abuse and are unable to quit or have mental disorders. 17. People with a history of peripheral nervous system disease and muscle strength below grade 3. 18. Participants who have participated in or are conducting other clinical trials of anti-tumor drugs within four weeks. 19.Patients with concomitant diseases that, in the investigator's judgment, seriously endanger the patient's safety or interfere with the patient's completion of the study.

研究实施时间：

Study execute time：

从 From 2025-04-01 00:00:00至 To 2030-04-01 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2025-05-01 00:00:00 至 To 2026-12-31 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	23
Group：	Experimental group	Sample size：	23
干预措施：	安罗替尼联合碘131	干预措施代码：
Intervention：	Anlotinib with 131I	Intervention code：

组别：	对照组	样本量：	24
Group：	Control group	Sample size：	24
干预措施：	碘131	干预措施代码：
Intervention：	131I	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(区县)：
Country：	China	Province：	Tianjin	City：
单位(医院)：	天津医科大学总医院	单位级别：	三甲
Institution hospital：	Tianjin Medical University General 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：	ORR	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	甲状腺球蛋白	指标类型：	主要指标
Outcome：	Tg	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：	DCR	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	指标类型：	主要指标
Outcome：	AE	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：	PFS	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	生活质量评分	指标类型：	主要指标
Outcome：	HRQoL	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：

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）：	点击下载
Calculated Results after the Study Completed(upload file)：	download

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）：	研究入组结束后,会同步发表国际大会或者全文,研究者联系方式。
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	After the study enrollment, the international conference or full text will be published simultaneously. Contact information of the researcher.
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：	病例报告表
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：	2025-04-07 17:47:07