ChiCTR2400084482 版本V1.0 版本创建时间2024/05/17 11:06:41 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：

ChiCTR2400084482 

最近更新日期：

Date of Last Refreshed on：

2024-05-17 11:01:39 

注册时间：

Date of Registration：

2024-05-17 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

卡瑞利珠单抗联合阿帕替尼治疗复发脊索瘤患者的安全性及有效性研究

Public title：

Camrelizumab combined with Apatinib in the treatment of recurrent spine Study on the safety and effectiveness of patients with chordoma

注册题目简写：

English Acronym：

研究课题的正式科学名称：

卡瑞利珠单抗联合阿帕替尼治疗复发脊索瘤患者的安全性及有效性研究

Scientific title：

Camrelizumab combined with Apatinib in the treatment of recurrent spine Study on the safety and effectiveness of patients with chordoma

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：

陈赞 

研究负责人：

陈赞 

Applicant：

Chen Zan 

Study leader：

Chen Zan 

申请注册联系人电话：

Applicant telephone：

+86 139 1171 2120

研究负责人电话：

Study leader's telephone：

+86 139 1171 2120

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：

chenzan66@163.com

研究负责人电子邮件：

Study leader's E-mail：

chenzan66@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：

北京市西城区长椿街45号

研究负责人通讯地址：

北京市西城区长椿街45号

Applicant address：

No.45, Changchun Street, Xicheng District, Beijing

Study leader's address：

No.45, Changchun Street, Xicheng District, Beijing

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：

首都医科大学宣武医院

Applicant's institution：

xuanwu hospital capital medical university

研究负责人所在单位：

首都医科大学宣武医院

Affiliation of the Leader：

xuanwu hospital capital medical university

是否获伦理委员会批准：

是/Yes

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

临研审[2023]243号-003

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：

首都医科大学宣武医院伦理委员会

Name of the ethic committee：

Xuanwu hospital Ethics Committee of Capital Medical University

伦理委员会批准日期：

Date of approved by ethic committee：

2024-01-29 00:00:00

伦理委员会联系人：

沈芊

Contact Name of the ethic committee：

Shen Qian

伦理委员会联系地址：

北京市西城区长椿街45号

Contact Address of the ethic committee：

No.45, Changchun Street, Xicheng District, Beijing

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 10 8319 9270

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：

首都医科大学宣武医院

Primary sponsor：

xuanwu hospital capital medical university

研究实施负责（组长）单位地址：

北京市西城区长椿街45号

Primary sponsor's address：

No.45, Changchun Street, Xicheng District, Beijing

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

北京市

市(区县)：

西城区

Country：

China

Province：

Beijing

City：

Xicheng District

单位(医院)：

首都医科大学宣武医院

具体地址：

北京市西城区长椿街45号

Institution
hospital：

xuanwu hospital capital medical university

Address：

No.45, Changchun Street, Xicheng District, Beijing

经费或物资来源：

无

Source(s) of funding：

NONE

Target disease：

chordoma

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：

评价卡瑞利珠联合阿帕替尼对复发、化疗失败脊索瘤受试者的安全性、耐受性  

Objectives of Study：

To evaluate the safety and tolerability of Karelizumab combined with apatinib in patients with chordoma who have relapsed or failed chemotherapy.

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.年龄为≧18岁，男女不限； 2.东部肿瘤协作组（ECOG）体力状况评分为 0-1； 3.预期生存期≥3 个月； 4.经组织病理学证实的晚期脊索瘤患者； 5.有影像学可评估病灶，根据实体瘤疗效评估标准（RECIST 1.1，见附件2），至少有一个单径可测量病灶，其最长径采用螺旋CT测量≥ 10 mm； 6.既往抗肿瘤治疗所致的所有急性毒性反应在入组前缓解至 0-1 级（根据 NCI CTCAE 5.03 版）或者至入组/排除标准所规定的水平（脱发等研究者认为对受试者不产生安全性风险的毒性除外）；如果受试者接受了大手术，他们必须在开始治疗之前已经从并发症中充分恢复； 7.主要器官功能正常，即符合下列标准： （1）血常规检查标准需符合（14天内未输血及血制品，未使用G-CSF及其他造血刺激因子纠正）： a. 血红蛋白（Hb）≥ 80 g/L； b. 中性粒细胞数（ANC）≥ 1.5×109/L； c. 血小板计数（PLT）≥ 80×109/L； （2）生化检查需符合以下标准： a. 总胆红素（TBIL）< 1.5 ULN； b. 谷丙转氨酶（ALT）和谷草转氨酶（AST）< 2.5ULN，而对于肝转移患者则< 5ULN；碱性磷酸酶 < 5ULN； c. 血清Cr ≤ ULN或内生肌酐清除率 > 45 ml/min。 8.育龄妇女必须已经采取可靠的避孕措施或在入组前7天内进行妊娠试验（血清或尿液），且结果为阴性，并且愿意在试验期间和末次给予试验药物后60天采用适当的方法避孕。对于男性，须同意在试验期间和末次给予试验药物后120天内采用适当的方法避孕或已手术绝育； 9.受试者自愿加入本研究，并签署知情同意书，依从性好，配合随访。

Inclusion criteria

1. The age is ≧18 years old, regardless of sex; 2. The score of physical condition of the Eastern Cancer Cooperative Group (ECOG) is 0-1; 3. The expected survival time is ≥3 months; 4. Patients with advanced chordoma confirmed by histopathology; 5. There are lesions that can be evaluated by imaging. According to the evaluation standard of solid tumor curative effect (RECIST 1.1, see Annex 2), there is at least one single-diameter measurable lesion, and its longest diameter is measured by spiral CT ≥ 10 mm;; 6. All acute toxic reactions caused by previous anti-tumor treatments were relieved to 0-1 level (according to NCI CTCAE version 5.03) or to the level specified in the inclusion/exclusion criteria (except for the toxicity such as alopecia that researchers think does not pose a safety risk to the subjects); If the subjects have undergone major surgery, they must have fully recovered from the complications before starting treatment; 7. The main organs function normally, that is, they meet the following standards: (1) The standard of routine blood examination should meet (blood transfusion and blood products have not been given within 14 days, and G-CSF and other hematopoietic stimulating factors have not been used for correction): A. hemoglobin (HB) ≥ 80 g/l; B. Neutrophil count (ANC)≥ 1.5×109/L;/L; C. platelet count (PLT)≥ 80×109/L;/l; (2) Biochemical inspection shall meet the following standards: A. total bilirubin (TBIL)< 1.5 ULN;; B alanine aminotransferase (ALT) and aspartate aminotransferase (ast) are less than 2.5 uln, but less than 5 uln for patients with liver metastasis; Alkaline phosphatase < 5ULN;; C. serum Cr ≤ ULN or endogenous creatinine clearance rate > 45 ml/min. 8. Women of childbearing age must have taken reliable contraceptive measures or conducted a pregnancy test (serum or urine) within 7 days before entering the group, and the results are negative, and they are willing to adopt appropriate methods of contraception during the test period and 60 days after the last administration of the test drug. For men, they must agree to use appropriate methods of contraception or surgical sterilization during the trial and within 120 days after the last administration of the test drug; 9. The subjects volunteered to join the study and signed the informed consent form, which had good compliance and cooperated with the follow-up.

排除标准：

1.既往抗肿瘤治疗(同步放化疗、手术治疗)毒性未恢复(脱发、碱性磷酸酶、谷氨脱转肽酶(GGT)或经与研究者和申办方讨论可以入组的受试者除外 2.首次使用卡瑞利珠单抗前14天之内使用过免疫抑制药物，不包括喷鼻和吸入性皮质类固醇或生理剂量的系统性类固醇激素（即不超过10 mg/天强的松龙或同等药物生理学剂量的其他皮质类固醇）；? 3.既往接受过下列疗法：抗 PD-1、抗PD-L1、抗VEGFR抗体或抗PD-L2药物或者针对另一种刺激或协同抑制T 细胞受体（例如，CTLA-4、OX-40、CD137）的药物； 4.无法控制的高血压（收缩压 ≥ 150 mmHg或者舒张压 ≥ 90 mmHg，尽管进行了系统的药物治疗）； 5.患有严重的心血管疾病： Ⅱ级以上心肌缺血或心肌梗塞、控制不良的心律失常（包括QTc间期男性≥450 ms、女性≥470 ms）；Ⅲ～Ⅳ级心功能不全（根据纽约心脏学会NYHA分级，见附件3），或心脏彩超检查提示左室射血分数（LVEF）＜ 50%； 6.存在任何活动性自身免疫病或有自身免疫病病史（包括但不局限于：自身免疫性肝炎、间质性肺炎，葡萄膜炎、肠炎、垂体炎、血管炎、肾炎、甲状腺功能亢进、甲状腺功能降低）的患者不得纳入； 7.受试者进行支气管扩张剂等系统治疗，哮喘控制不满意，不能纳入（在童年期哮喘已完全缓解，成人后无需任何干预的可纳入）。? 8.尿常规提示尿蛋白≥ ++，或证实24小时尿蛋白量≥1.0g； 9.凝血功能异常（INR＞1.5 ULN或凝血酶原时间（PT）＞ULN+4秒或APTT >1.5 ULN），具有出血倾向或正在接受溶栓或抗凝治疗； 注：在凝血酶原时间国际标准化比值（INR）≤ 1.5的前提下，允许以预防目的使用小剂量肝素（成人每日用量为0.6万~1.2万U）或小剂量阿司匹林（每日用量 ≤ 100 mg）； 10.首次用药前4周内并发重度感染（如：需要静脉滴注抗生素、抗真菌或抗病毒药物），或在筛选期间/首次给药前出现不明原因的发热>38.5°C； 11.入组前12个月内发生严重的动/静脉血栓事件，如脑血管意外（包括暂时性缺血性发作、脑出血、脑梗塞）、深静脉血栓及肺栓塞等； 12.入组前4周内接受过重大外科手术或出现重度创伤性损伤、骨折或溃疡； 13.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）、活动性肺结核、活动性乙型肝炎（HBV DNA ≥ 500 IU/ml）、丙型肝炎（丙肝抗体阳性，且 HCV-RNA 高于分析方法的检测下限）或合并乙肝和丙肝共同感染者； 14.有明确过敏史的病人，可能对阿帕替尼和卡瑞利珠单抗的生物制剂潜在过敏或者不耐受； 15.有明显影响口服药物吸收的因素，如无法吞咽、慢性腹泻和肠梗阻等。或6个月内出现过空腔脏器窦道或穿孔； 16.具有精神类药物滥用史且无法戒除者或有精神障碍的； 增加参加研究或研究药物相关的风险，并且根据研究者的判断，可导致患者不适合入选研究的其他情况。

Exclusion criteria：

1. Except the subjects whose toxicity has not recovered from previous anti-tumor treatments (concurrent chemoradiotherapy and surgical treatment) (alopecia, alkaline phosphatase, transglutaminase (GGT) or who can be enrolled after discussion with researchers and sponsors. 2. Immunosuppressive drugs have been used within 14 days before the first use of Karelizumab, excluding nasal and inhaled corticosteroids or systemic steroid hormones with physiological dose (that is, no more than 10 mg/ day of prednisolone or other corticosteroids with the same drug physiological dose); 3. Previously received the following therapies: anti-PD-1, anti-PD-L1, anti-VEGFR antibody or anti-PD-L2 drugs, or drugs that stimulate or synergistically inhibit T cell receptors (for example, CTLA-4, OX-40, CD137); 4. Uncontrollable hypertension (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 90 mmHg, despite systematic drug treatment); 5. Suffering from serious cardiovascular diseases: myocardial ischemia or myocardial infarction above grade II, and poorly controlled arrhythmia (including QTc interval ≥450 ms for men and ≥ 470 ms for women); Ⅲ ~ Ⅳ cardiac insufficiency (according to NYHA classification of new york Heart Association, see Annex 3), or left ventricular ejection fraction (LVEF) indicated by color Doppler echocardiography < 50%; 6. Patients with any active autoimmune disease or a history of autoimmune disease (including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism and hypothyroidism) shall not be included; 7. Subjects were treated with systemic therapy such as bronchodilators, and their asthma control was not satisfactory, so they could not be included (asthma was completely relieved in childhood, and adults could be included without any intervention). 8. Urine routine indicates that urine protein is ≥++,or it is confirmed that the amount of urine protein in 24 hours is ≥ 1.0g; 9. Abnormal coagulation function (INR>1.5 ULN or prothrombin time (PT) > ULN+4 seconds or APTT >1.5 ULN), bleeding tendency or undergoing thrombolytic or anticoagulant therapy; Note: On the premise that the international normalized ratio (INR) of prothrombin time INR)≤ 1.5, it is allowed to use low-dose heparin (the daily dosage for adults is 0.6 ~ 12,000 U) or low-dose aspirin (the daily dosage is ≤ 100 mg) for preventive purposes; 10. Severe infection (such as intravenous drip of antibiotics, antifungal or antiviral drugs) occurred within 4 weeks before the first administration, or unexplained fever > 38.5°C; occurred during the screening period/before the first administration; 11. Serious arterial/venous thrombosis events occurred within 12 months before joining the group, such as cerebrovascular accident (including temporary ischemic attack, cerebral hemorrhage and cerebral infarction), deep venous thrombosis and pulmonary embolism; 12. Have received major surgery or severe traumatic injury, fracture or ulcer within 4 weeks before joining the group; 13. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), active pulmonary tuberculosis, active hepatitis B (HBV DNA ≥ 500 IU/ml), hepatitis C (hepatitis C antibody is positive and HCV-RNA is higher than the detection limit of the analysis method) or hepatitis B and hepatitis C co-infection; 14. Patients with a clear allergic history may be potentially allergic or intolerant to the biological preparations of apatinib and carrelizumab; 15. There are obvious factors that affect the absorption of oral drugs, such as inability to swallow, chronic diarrhea and intestinal obstruction. Or sinus or perforation of hollow organs occurred within 6 months; 16. Those who have a history of psychotropic drug abuse and cannot quit or have mental disorders; Increase the risk associated with participating in the study or studying drugs, and according to the researcher's judgment, it may lead to other situations in which patients are not suitable for the study.

研究实施时间：

Study execute time：

从 From 2024-02-01 00:00:00至 To 2026-02-01 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2024-06-01 00:00:00 至 To 2026-01-01 00:00:00  

干预措施：

Interventions：

组别：

1

样本量：

30

Group：

ONE

Sample size：

干预措施：

卡瑞利珠单抗： PD-1抗体SHR-1210：SHR-1210静脉滴注给药，固定剂量 200 mg，以 30分钟时间静脉滴注（包括冲管时间在内整体滴注时间不短于 20分钟，不长于60分钟），每2周 1次，持续用药直到疾病进展毒性不能耐受以及接受接受免疫治疗最长不超过2年； 阿帕替尼： 250 mg，每日口服，餐后约半小时服用（每日服药的间应尽可能相同），以温开水送服。 卡瑞利珠单抗联合阿帕替尼，每2周为一个治疗周期，联合用药直至疾病进展或出现无法耐受的毒性反应。

干预措施代码：

Intervention：

Camrelizumab: PD-1 antibody SHR-1210: SHR-1210 is administered intravenously, with a fixed dose of 200 mg, for 30 minutes (the overall infusion time is not less than 20 minutes and not more than 60 minutes including the tube flushing time), once every two weeks, and the drug is continued until the disease progresses and the toxicity is intolerable and the immunotherapy is received for no more than 2 years; Apatinib: 250 mg, taken orally every day, about half an hour after meals (the interval of taking medicine every day should be the same as possible), and taken with warm water. Karelizumab combined with apatinib, every two weeks is a treatment cycle, and they are combined until the disease progresses or intolerant toxic reactions appear.

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 北京市 

市(区县)：

 西城区 

Country：

China 

Province：

beijing 

City：

Xicheng District 

单位(医院)：

首都医科大学宣武医院 

单位级别：

三甲 

Institution
hospital：

xuanwu hospital capital medical university

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

安全性

指标类型：

主要指标

Outcome：

Safety

Type：

Primary indicator

测量时间点：

试验开始到结束后1个月

测量方法：

AE发生率及其严重程度

Measure time point of outcome：

From beginning to one month after the end of the study

Measure method：

Incidence and severity of AE

指标中文名：

无进展生存期

指标类型：

主要指标

Outcome：

efficiency

Type：

Primary indicator

测量时间点：

试验开始到结束

测量方法：

影像学评价无进展生存期

Measure time point of outcome：

From beginning to the end of the study

Measure method：

Radiology evaluation of progression-free time

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：

从开始到死亡

测量方法：

死亡时间

Measure time point of outcome：

From beginning to death

Measure method：

Death time

指标中文名：

客观缓解率

指标类型：

次要指标

Outcome：

Objective remission rate

Type：

Secondary indicator

测量时间点：

1月，3月，6月

测量方法：

影像评价实体瘤缓解程度（RECIST 1.1）

Measure time point of outcome：

1st month, 3rd month, 6th month

Measure method：

Radiology evaluation of solid tumor alleviation (RECIST 1.1)

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：

1月，3月，6月

测量方法：

症状稳定及影像评估无进展率

Measure time point of outcome：

1st month, 3rd month, 6th month

Measure method：

symptom stability and imaging evaluation non-progression rate

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：

标本中文名：

尿液

组织：

Sample Name：

urine

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 100 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

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）：

2026年2月1日

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

February 1, 2026

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：

Case Record Form

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：

  2024-05-17 11:01:39