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：	ChiCTR2500102436
最近更新日期： Date of Last Refreshed on：	2025-05-14 17:06:11
注册时间： Date of Registration：	2025-05-14 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贝莫苏拜单抗一线治疗晚期嗜铬细胞瘤/副神经节瘤的单臂、多中心、前瞻性、II 期临床研究
Public title：	A Single-Arm, Multicenter, Prospective Phase II Clinical Study of Anlotinib Hydrochloride Capsules Combined with Bempegaldesleukin as First-Line Treatment for Advanced Pheochromocytoma/Paraganglioma
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贝莫苏拜单抗一线治疗晚期嗜铬细胞瘤/副神经节瘤的单臂、多中心、前瞻性、II 期临床研究
Scientific title：	A Single-Arm, Multicenter, Prospective Phase II Clinical Study of Anlotinib Hydrochloride Capsules Combined with Bempegaldesleukin as First-Line Treatment for Advanced Pheochromocytoma/Paraganglioma
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：	郭胜杰	研究负责人：	郭胜杰
Applicant：	Guo Shengjie	Study leader：	Guo Shengjie
申请注册联系人电话： Applicant telephone：	+86 134 1614 0919	研究负责人电话： Study leader's telephone：	+86 134 1614 0919
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：	guoshj@sysucc.org.cn	研究负责人电子邮件： Study leader's E-mail：	guoshj@sysucc.org.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：	广东省广州市越秀区东风东路651号中山大学肿瘤防治中心	研究负责人通讯地址：	广东省广州市越秀区东风东路651号中山大学肿瘤防治中心
Applicant address：	Cancer Center, Sun Yat-sen University, 651 Dongfeng East Road, Yuexiu District, Guangzhou, Guangdong Province, China	Study leader's address：	Cancer Center, Sun Yat-sen University, 651 Dongfeng East Road, Yuexiu District, Guangzhou, Guangdong Province, 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：	中山大学肿瘤防治中心
Applicant's institution：	Sun Yat-sen University Cancer Center
研究负责人所在单位：	中山大学肿瘤防治中心
Affiliation of the Leader：	Sun Yat-sen University Cancer Center

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：	SL-B2024-025-05	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：	中山大学肿瘤防治中心伦理委员会
Name of the ethic committee：	Ethics Committee of Sun Yat-sen University Cancer Center
伦理委员会批准日期： Date of approved by ethic committee：	2024-11-01 00:00:00
伦理委员会联系人：	潘旭芝
Contact Name of the ethic committee：	Pan Xuzhi
伦理委员会联系地址：	广东省广州市越秀区先烈南路华泰宾馆翠园楼
Contact Address of the ethic committee：	Cuiyuan Building, Huatai Hotel, Xianlie South Road, Yuexiu District, Guangzhou City, Guangdong Province
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 20 8734 3009	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：

中山大学肿瘤防治中心

Primary sponsor：

Sun Yat-sen University Cancer Center

研究实施负责（组长）单位地址：

广东省广州市越秀区东风东路651号

Primary sponsor's address：

651 Dongfeng East Road, Yuexiu District, Guangzhou, Guangdong Province, 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)：	广东	市(区县)：
Country：	China	Province：	Guangdong	City：
单位(医院)：	中山大学肿瘤防治中心	具体地址：	广东省广州市越秀区东风东路651号
Institution hospital：	Sun Yat-sen University Cancer Center	Address：	651 Dongfeng East Road, Yuexiu District, Guangzhou, Guangdong Province, China

经费或物资来源：

安罗替尼和贝莫苏拜单抗药物均由正大天晴公司免费提供

Source(s) of funding：

Anlotinib and bermosubamab were provided free of charge by Chia Tai Tianqing Company

研究疾病：

嗜铬细胞瘤/副神经节瘤

Target disease：

Pheochromocytoma/paraganglioma

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：

单臂

Study design：

Single arm

研究目的：

观察和评价盐酸安罗替尼胶囊联合贝莫苏拜单抗一线治疗晚期嗜铬细胞瘤/副神经节瘤的疗效与安全性

Objectives of Study：

To observe and evaluate the efficacy and safety of anlotinib hydrochloride capsules combined with bermosubamab as first-line treatment for advanced pheochromocytoma/paraganglioma

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. Patients voluntarily participated in this study and signed informed consent.
2. patients aged >=18 and  <=75 years old;
3. ECOG score <=2; The expected survival time was >=6 months.
4. Advanced pheochromocytoma/paraganglioma diagnosed by pathology: including clinical stage IV pheochromocytoma/paraganglioma that could not be resected, postoperative recurrence or metastasis;
5. unwilling or not suitable for chemotherapy and radionuclide therapy.
6. at least one measurable lesion (RECIST 1.1);
7. The main organs function was good, and the laboratory examination indicators met:
Blood routine examination:
(1) Hemoglobin (HB) >= 90g/L(5.6 mmol/L);
(2) Absolute neutrophil count (ANC) >=1.5×10^9/L; White blood cell count >=3.5×10^9/L;
(3) Platelet (PLT) >= 80×10^9/L;
Blood biochemical tests:
(1) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=2.5 × ULN (liver metastasis/bone metastasis <=5 × ULN; Tumor bone metastasis <=5 ULN).
(2) Serum total bilirubin (TBIL) <=1.5 × ULN;
(3) Serum creatinine Cr<=1.5×ULN or creatinine clearance >=60 ml/min; Blood urea nitrogen (BUN) <=2.5 × upper limit of normal value (ULN);
(4) albumin (ALB) >=30 g/L;
Coagulation function tests:
(1) Activated partial thromboplastin time (APTT), international normalized ratio (INR), prothrombin time (PT) <= 1.5×ULN;
(2) Women of childbearing age must confirm their non-pregnancy status before enrollment. All enrolled subjects (male or female) should take adequate contraceptive measures during the whole treatment period and for 4 weeks after the end of treatment;
(3) Subjects voluntarily participated in this study and were willing to return to the hospital for follow-up, with good compliance;
Myocardial enzymes and ejection fraction were normal.

排除标准：

1.已知对盐酸安罗替尼胶囊、贝莫苏拜单抗活性成分或任何辅料有过敏反应； 2.入组前接受抗肿瘤单克隆抗体或其他研究药物治疗；既往曾接受过其他抗 PD-1 单抗治疗或其他针对 PD-1／PD-L1 的药物治疗； 3.既往使用过盐酸安罗替尼胶囊或其他抗血管生成药物，如舒尼替尼、贝伐珠单抗等； 4.患者正在使用免疫抑制剂或全身激素治疗以达到免疫抑制目的（剂量大于 10mg／天泼尼松或其他等效激素），并于入组前 2 周内仍在使用； 5.患者存在任何活动性自身免疫病或有自身免疫病病史；有未能控制良好的心脏临床症状或疾病； 6.患者先天或后天免疫功能缺陷； 7.入组前 4 周内有消化道穿孔史或开放性活检史；≥CTCAE 3 级的任何出血事件、存在未愈合创口、溃疡或骨折； 8.入组前 6 月内发生过动／静脉血栓事件，如心血管-脑血管以外（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；不稳定型心律失常、因不稳定型心绞痛或心肌 9.梗死入院行心脏血管成形术或冠脉搭桥手术； 10.有活动性出血或出血倾向者； 11.校正 QT 间期＞ 480msec；如果患者存在 QT 间期延长，但研究者研究评估延长的原因为心脏起搏器（且无心脏其他异常），需要与申办方研究医师讨论后决定患者是否为适合入组研究； 12.怀疑患有其他原发癌的患者；研究前 5 年内患有其他原发性恶性肿瘤的患者（充分治疗的原位宫颈癌或皮肤癌，如基底细胞癌、鳞状细胞癌或非黑色素瘤性皮肤癌等除外）； 13.合并疾病/病史：（1）入组前 3 个月内出现临床显著的咯血（每日咯血大于 50ml）；或显著临床意义的出血症状或具有明确的出血倾向，如消化道出血、出血性胃溃疡、基线期大便潜血及以上，或患有脉管炎等；（2）高血压，且经降压药物治疗无法获得良好控制（收缩压≥150 mmHg或者舒张压≥100mmHg）；随机前 6 个月内，出现以下情况：心肌梗死、严重/不稳定型心绞痛、NYHA 2 级以上心功能不全、有临床意义的室上性或室性心律失常以及症状性充血性心力衰竭；（3）间质性肺病、非感染性肺炎或无法控制的系统性疾病（如：糖尿病控制不良(空腹血糖(FBG)＞10mmol/ L)、肺纤维化和急性肺炎等）；（4）肾功能衰竭需要血液透析或腹膜透析；（5）肝硬化、失代偿性肝病、活动性肝炎（乙型肝炎，定义为 HBV-DNA≥ 500 IU/ml；丙型肝炎，定义为 HCV-RNA 高于分析方法的检测下限）或慢性肝炎需要抗病毒治疗；（6）首次研究用药前 28 天内减毒活疫苗接种史或者预计研究期间行减毒活疫苗接种；（7）人类免疫缺陷病毒（HIV）感染或已知有获得性免疫缺陷综合征（艾滋病）；合并乙肝和丙肝共同感染；（8）首次给药前 4 周内存在重度感染，包括但不限于需住院治疗的菌血症、重症肺炎等；首次给药前 2 周内存在需使用系统抗生素治疗的CTCAE≥2 级的活动性感染，或在筛选期间/首次给药前出现不明原因的发热>38.5°C（经研究者判断，因肿瘤原因导致的发热可入组）；给药前 1 年内有活动性结核感染证据；（9）随机前 28 天之内进行过大手术（因诊断需要进行的组织活检和经外周静脉穿刺置入中心静脉导管操作[PICC]或输液港(PORT)是允许的）；（10）既往接受过或准备接受同种异体骨髓移植或实体器官移植的受试者；（11）周围神经病变≥2 级者；活动性的脑转移、癌性脑膜炎、脊髓压迫患者，或筛选时影像学 CT 或 MRI 检查发现脑或软脑膜的疾病（入组前 14 天已完成治疗且症状稳定的脑转移患者可以入组，但需经颅脑MRI、CT 或静脉造影评价确认为无脑出血症状）；（12）具有明显影响口服药物吸收的因素，如无法吞咽、慢性腹泻、存在具有显著临床意义的肠梗阻。 14.妊娠期、哺乳期、计划在研究期间妊娠的女性受试者或有生育能力但不愿采取适当避孕措施的男性或女性。 15.存在其他严重身体或精神疾病或实验室检查异常，可能增加参与研究的风险，或干扰研究结果，以及研究者认为（15）不适合参与本研究的患者； 16.脑转移患者； 17.影像学显示肿瘤已侵犯重要血管或随访中判断肿瘤极有可能侵犯重要血管并造成致死性出血； 18.正在使用与盐酸安罗替尼胶囊/贝莫苏拜单抗相互拮抗作用的药物；

Exclusion criteria：

1. known allergic reaction to anlotinib hydrochloride capsules, the active ingredient of bermosubamab, or any excipients; 2. patients received anti-tumor monoclonal antibodies or other study drugs before enrollment; Prior treatment with other anti-PD-1 monoclonal antibodies or other PD-1 / PD-L1 drugs; 3. previous use of anlotinib hydrochloride capsules or other anti-angiogenic drugs, such as sunitinib, bevacizumab, etc.; 4. patients were receiving immunosuppressive or systemic hormone therapy for immunosuppression (prednisone at a dose greater than 10mg/day or equivalent) within 2 weeks before enrollment; 5. patients with any active autoimmune disease or a history of autoimmune disease; Patients with uncontrolled cardiac symptoms or diseases; 6. patients with congenital or acquired immune deficiency; 7. history of gastrointestinal perforation or open biopsy within 4 weeks before enrollment; Any bleeding events >=CTCAE grade 3, the presence of unhealed wounds, ulcers, or fractures; 8. arterial/venous thrombosis events occurred within 6 months before enrollment, such as non-cardio-cerebrovascular events (including transient ischemic attack), deep vein thrombosis (except venous thrombosis caused by venous catheterization due to previous chemotherapy, which was judged by the investigator to be cured), and pulmonary embolism. "Unstable arrhythmia, due to unstable angina pectoris, or myocardium. 9. Admission for cardiac angioplasty or coronary artery bypass grafting; 10. patients with active bleeding or bleeding tendency; 11. corrected QT interval > 480msec; If a patient had a prolongation of the QT interval that was assessed by the investigator as being due to the pacemaker (and in the absence of other cardiac abnormalities), a decision about enrollment was made after discussion with the sponsor research physician. 12. patients with suspected other primary cancers; Patients with other primary malignancies within 5 years before the study (except adequately treated cervical cancer or skin cancer in situ, such as basal cell carcinoma, squamous cell carcinoma, or nonmelanoma skin cancer); 13. Comorbidities/Medical history: (1) Clinically significant hemoptysis (> 50ml/day) within 3 months before enrollment; Or clinically significant bleeding symptoms or a clear bleeding tendency, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood or above, or angiitis; (2) hypertension that is not well controlled by antihypertensive medication (systolic blood pressure >=150 mmHg or diastolic blood pressure >=100mmHg); Within 6 months before randomization, myocardial infarction, severe or unstable angina, NYHA class 2 or higher cardiac dysfunction, clinically significant supraventricular or ventricular arrhythmias, and symptomatic congestive heart failure occurred; (3) Interstitial lung disease, non-infectious pneumonia or uncontrolled systemic diseases such as poorly controlled diabetes (fasting blood glucose > 10mmol/ L), pulmonary fibrosis and acute pneumonia; (4) renal failure requiring hemodialysis or peritoneal dialysis; (5) Liver cirrhosis, decompensated liver disease, active hepatitis (hepatitis B, defined as HBV-DNA≥ 500 IU/ml; Hepatitis C, defined as HCV-RNA above the lower detection limit of the assay) or chronic hepatitis requiring antiviral therapy; (6) vaccination history of live attenuated vaccine within 28 days before the first study medication or expected vaccination during the study period; (7) Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS); Co-infection of hepatitis B and C; (8) Severe infection within 4 weeks before the first dose, including but not limited to bacteremia requiring hospitalization, severe pneumonia, etc. Active infection of CTCAE grade >=2 requiring treatment with systemic antibiotics within 2 weeks before the first dose or unexplained fever >38.5°C during screening or before the first dose (fever due to cancer, as judged by the investigator, was eligible); Evidence of active tuberculosis infection within 1 year before administration; (9) Major surgery within 28 days before randomization (diagnostic biopsy and peripherally inserted central catheter [PICC] or PORT access (PORT) were permitted); (10) Prior bone marrow or solid organ transplantation or preparation for allogeneic transplantation; (11) peripheral neuropathy grade >=2; Patients with active brain metastases, cancer meningitis, spinal cord compression, or brain or leptomeningeal disease on screening imaging CT or MRI (patients with symptomatic stable brain metastases who had completed treatment 14 days before enrollment were eligible if they had no signs of cerebral hemorrhage as confirmed by evaluation of brain MRI, CT, or venography). (12) Factors that clearly affect the absorption of oral medication include inability to swallow, chronic diarrhoea, and the presence of clinically significant intestinal obstruction. 14. Female subjects who are pregnant, breastfeeding, planning to become pregnant during the study, or men or women who are fertile but unwilling to use appropriate contraception. 15. patients with other serious physical or mental illnesses or laboratory abnormalities that may increase the risk of participating in the study or interfere with the study results, and the investigator considers (15) patients to be unsuitable for participating in the study; 16. patients with brain metastases; 17. Imaging showed that the tumor had invaded important blood vessels or the tumor was highly likely to invade important blood vessels and cause fatal hemorrhage during follow-up; 18. taking drugs with antagonistic effects with anlotinib hydrochloride capsules/bermosubemab;

研究实施时间：

Study execute time：

从 From 2025-05-01 00:00:00至 To 2029-05-01 00:00:00

征募观察对象时间：

Recruiting time：

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

干预措施：

Interventions：

组别：	试验组	样本量：	22
Group：	Test group	Sample size：	22
干预措施：	贝莫苏拜单抗 1200mg i.v.gtt q3w；安罗替尼12 mg 口服，持续 14 天，停药 7 天，21 天为 1 疗程	干预措施代码：
Intervention：	Bectumomab 1200mg i.v.gtQ3w; Anlotinib was given orally at a dose of 12 mg for 14 days followed by 7 days off for a course of 21 days	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	广东	市(区县)：
Country：	Chian	Province：	Guangdong	City：
单位(医院)：	中山大学肿瘤防治中心	单位级别：	三甲
Institution hospital：	Sun Yat-sen University Cancer Center	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：	持续缓解时间	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：	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：	不良事件	指标类型：	副作用指标
Outcome：	Adverse events	Type：	Adverse events
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	严重不良事件	指标类型：	副作用指标
Outcome：	Serious Adverse events	Type：	Adverse events
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）：	1.试验完成6个月内公开；2.通过中国临床试验注册中心平台；3.网址：www.medreaman.org.cn。
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	1. Disclosure within 6 months after completion of the trial; 2. Through the Chinese Clinical Trial Registry platform; 3. Website: www.medreaman.org.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：	1. 填写病历记录表（case record form,CRF）,病历记录表由研究者负责填写和保管，每次填写前先核对病历封面的参试者真实姓名和参试者编号，每位受试者治疗及随访结束后的3个工作日内，完成CRF的填写，便于数据录入人员和监察员核对；2.本研究的所有数据均上传至临床研究公共管理平台（Research Manager,ResMan）,实现数据共享，由数据录入人员负责将CRF中的数据信息，录入ResMan系统。
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	1. Fill in the case record form (CRF), which is filled and kept by the researcher. Before filling in the form, check the real name and number of the participant on the cover of the medical record. Facilitate data entry personnel and inspectors to check; 2. All data of this study were uploaded to the Research Manager (ResMan) for data sharing. Data entry personnel were responsible for inputting data information in CRF into ResMan system.
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：	2025-05-14 17:05:12