ChiCTR2500099005 版本V1.0 版本创建时间2025/03/17 16:21:38 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：

 ChiCTR2500099005 

最近更新日期：

Date of Last Refreshed on：

 2025-03-17 16:21:20 

注册时间：

Date of Registration：

 2025-03-17 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

索凡替尼联合特瑞普利单抗联合化疗方案二线治疗不能手术切除的局部晚期、复发或转移性胆道系统肿瘤患者的单臂、开放性、单中心临床研究

Public title：

A single-arm, open-label, single-centered clinical trial to evaluate the efficacy and safety of surufatinib and tislelizumab in combination with chemotherapy in the second-line treatment of patients with unresectable locally advanced, recurrent or metastatic biliary tract carcinoma

注册题目简写：

English Acronym：

研究课题的正式科学名称：

索凡替尼联合特瑞普利单抗联合化疗方案二线治疗不能手术切除的局部晚期、复发或转移性胆道系统肿瘤患者的单臂、开放性、单中心临床研究

Scientific title：

A single-arm, open-label, single-centered clinical trial to evaluate the efficacy and safety of surufatinib and toripalimab in combination with chemotherapy in the second-line treatment of patients with unresectable locally advanced, recurrent or metastatic biliary tract carcinoma

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：

杨成成 

研究负责人：

锁爱莉/杨成成 

Applicant：

Yang Chengcheng 

Study leader：

Suo Aili/ Yang Chengcheng 

申请注册联系人电话：

Applicant telephone：

 +86 138 9286 5924

研究负责人电话：

Study leader's
telephone：

+86 29 8532 4600

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：

 ccyang@xjtufh.edu.cn

研究负责人电子邮件：

Study leader's E-mail：

 ccyang@xjtufh.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：

陕西省西安市雁塔区雁塔西路277号

研究负责人通讯地址：

陕西省西安市雁塔区雁塔西路277号

Applicant address：

No.277, West Yanta Road, Yanta District, Xi'an, Shaanxi, China

Study leader's address：

No.277, West Yanta Road, Yanta District, Xi'an, Shaanxi, 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：

西安交通大学第一附属医院

Applicant's institution：

The First Affiliated Hospital of Xi'an Jiaotong University

研究负责人所在单位：

西安交通大学第一附属医院

Affiliation of the Leader：

The First Affiliated Hospital of Xi'an Jiaotong University

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伦审科字第(530)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：

西安交通大学医学院第一附属医院医学伦理委员会

Name of the ethic committee：

Ethics Committee of The First Affiliated Hospital of Xi'an Jiaotong University

伦理委员会批准日期：

Date of approved by ethic committee：

 2023-12-08 00:00:00

伦理委员会联系人：

易秋月

Contact Name of the ethic committee：

Yi Qiuyue

伦理委员会联系地址：

陕西省西安市雁塔区雁塔西路277号

Contact Address of the ethic committee：

No.277, West Yanta Road, Yanta District, Xi'an, Shaanxi, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 29 8532 3473

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：

西安交通大学医学院第一附属医院

Primary sponsor：

The First Affiliated Hospital of Xi'an Jiaotong University

研究实施负责（组长）单位地址：

陕西省西安市雁塔区雁塔西路277号

Primary sponsor's address：

No.277, West Yanta Road, Yanta District, Xi'an, Shaanxi, 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)：

陕西

市(区县)：

西安

Country：

China

Province：

Shaanxi

City：

Xi'an

单位(医院)：

西安交通大学医学院第一附属医院

具体地址：

陕西省西安市雁塔区雁塔西路277号

Institution
hospital：

The First Affiliated Hospital of Xi'an Jiaotong University

Address：

No.277, West Yanta Road, Yanta District, Xi'an, Shaanxi, China

经费或物资来源：

自筹经费

Source(s) of funding：

Self-funded

研究疾病：

胆道系统肿瘤  

Target disease：

Biliary Tract Carcinoma

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：

主要研究目的 观察和评价索凡替尼联合特瑞普利单抗联合化疗方案二线治疗不能手术切除的局部晚期或复发转移性胆道系统肿瘤患者的无进展生存期（PFS）。 次要研究目的 观察和评价索凡替尼联合特瑞普利单抗联合化疗方案二线治疗不能手术切除的局部晚期或复发转移性胆道系统肿瘤患者在客观缓解率（ORR）、疾病控制率（DCR）和总生存期（OS）等方面的有效性。 观察和评价索凡替尼联合特瑞普利单抗联合化疗方案二线治疗不能手术切除的局部晚期或复发转移性胆道系统肿瘤患者的安全性。  

Objectives of Study：

Primary objective To observe and evaluate the progression-free survival (PFS) of surufatinib combined with toripalimab combined with chemotherapy regimen in the second-line treatment of patients with unresectable locally advanced or recurrent metastatic biliary tract carcinoma. Secondary objectives To observe and evaluate the efficacy in terms of objective response rate (ORR), disease control rate (DCR) and overall survival (OS) of surufatinib combined with toripalimab combined with chemotherapy regimen as second-line treatment in patients with unresectable locally advanced or recurrent metastatic biliary tract carcinoma tumors. To observe and evaluate the safety of surufatinib combined with toripalimab combined with chemotherapy regimen in the second-line treatment of patients with unresectable locally advanced or recurrent metastatic biliary tract carcinoma.

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：18岁-80岁（包括18岁和80岁）； 2.经组织学或细胞学证实的手术不可切除或转移性晚期胆道系统腺癌，包括肝外胆管癌（EHCC）、肝内胆管癌（IHCC）或胆囊癌（GBC）； 3.接受过一线标准化疗失败、进展或毒性不可耐受的局部晚期或复发转移性疾病患者；接受过一种方案的辅助或新辅助化疗并且在化疗结束后＜ 6个月复发的可以入组； 4.已经获批的具有抗肿瘤适应症的中成药末次给药是在至少2周前完成的可以入组； 5.肝功能Child-Pugh A级（5-6分）或者较好的B级（≤7分）（见附录3）； 6.ECOG评分≤2分（见附录1）； 7.预期生存≥12周； 8.至少有一个可测量病灶（RECIST 1.1标准，见附录2）； 9.主要器官和骨髓功能基本正常： (1)血常规：白细胞≥ 3.5 x 10^9/L，中性粒细胞≥ 1.5 x 10^9/L，血小板≥ 80 x 10^9/L，血红蛋白≥ 90g/L； (2)国际标准化比率（INR）≤1.5×正常值上限（ULN），且活化部分凝血活酶时间（APTT）≤1.5×ULN； (3)肝功能：总胆红素≤ 1.5 x ULN ；无肝转移时，ALT/AST /ALP ≤ 2.5 x ULN；有肝转移时，ALT/AST /ALP ≤ 5 x ULN； (4)肾功能：血清肌酐≤ 1.5 x ULN，且肌酐清除率（CCr） 60mL/min（见附录6）； (5)心功能正常，二维心脏超声检测的左室射血分数(LVEF ) ≥ 50%。 10.对本研究充分了解，自愿参加，并且签署知情同意书。 11.有生育能力的男性或女性患者自愿在研究期间和末次研究用药6个月内使用有效的避孕方法，例如双重屏障式避孕方法、避孕套、口服或注射避孕药物、宫内节育器等。所有女性患者将被认为具有生育能力，除非该女性患者已自然绝经、已行人工绝经或绝育术（如子宫切除、双侧附件切除或放射性卵巢照射等）。

Inclusion criteria

1. 18 to 80 year-old (including 18 and 80 years); 2. Histologically or cytologically confirmed surgically unresectable or metastatic advanced biliary tract adenocarcinoma, including extrahepatic cholangiocarcinoma (EHCC), intrahepatic cholangiocarcinoma (IHCC), or gallbladder cancer (GBC); 3. Patients with locally advanced or recurrent metastatic disease who have failed, progressed, or have intolerable toxicity to first-line standard chemotherapy; patients who have received one regimen of adjuvant or neoadjuvant chemotherapy and have recurrence < 6 months after the end of chemotherapy can be enrolled; 4. The last dose of approved Chinese patent medicines with anti-tumor indications is completed at least 2 weeks ago can be enrolled; 5. Liver function Child-Pugh class A (5-6 points) or better class B (<= 7 points) (see Appendix 3); 6. ECOG score <= 2 (see Appendix 1); 7. Expected survival >= 12 weeks; 8. At least one measurable lesion (RECIST 1.1 criteria, see Appendix 2); 9. Basically normal function of main organs and bone marrow: (1) Blood routine: WBC >= 3.5 x 10^9/L, neutrophils >= 1.5 x 10^9/L, platelet >= 80 x 10^9/L, hemoglobin >= 90 g/L; (2) International normalized ratio (INR) <= 1.5 × upper limit of normal (ULN), and activated partial thromboplastin time (APTT) <= 1.5 × ULN; (3) Liver function: total bilirubin <= 1.5 x ULN; ALT/AST/ALP <= 2.5 x ULN in the absence of liver metastasis; ALT/AST/ALP <= 5 x ULN in the presence of liver metastasis; (4) Renal function: serum creatinine <= 1.5 x ULN, and creatinine clearance (CCr) 60 mL/min (see Appendix 6); (5) Normal cardiac function, left ventricular ejection fraction (LVEF) >= 50% measured by two-dimensional cardiac ultrasound. 10. Fully understand the study, volunteer to participate, and sign the informed consent form. 11. Male or female patients of childbearing potential voluntarily use effective contraceptive methods during the study and within 6 months after the last dose of study drug, such as double-barrier contraceptive methods, condoms, oral or injectable contraceptives, intrauterine devices, etc. All female patients will be considered to be of childbearing potential unless they are postmenopausal, have undergone artificial menopause, or have been surgically sterilized (e.g., hysterectomy, bilateral adnexectomy, or radiation ovarian irradiation).

排除标准：

1.入组前4周内接受过已获批的或在研的系统抗肿瘤治疗以及针对靶病灶的局部治疗； 2.研究者确定肝脏转移灶占肝脏总体积的50%或者以上； 3.经临床干预的胆道梗阻在首次研究药物治疗前14天研究者判断尚未缓解或需要抗感染治疗； 4.既往接受过肝移植； 5.患有未经治疗的有症状的中枢神经系统转移，既往接受过系统性、根治性脑或脑膜转移治疗（放疗或手术），如影像学证实稳定已维持至少1个月，且已停止全身性激素治疗（剂量>10mg/天泼尼松或其他等疗效激素）大于2周、无临床症状者可以纳入 6.入组前4周内参加过其它国内尚未获批或未上市的药物临床试验且接受了相应试验药物治疗； 7.入组开始前4周内接受过任何手术或有创的治疗或操作（静脉置管、穿刺引流、胆道支架植入减黄治疗等除外）； 8.患者目前存在药物未能控制的高血压，规定为：收缩压≥140 mmHg 和/或舒张压≥90 mmHg； 9.患者目前有任何影响药物吸收的疾病或状态，或患者不能口服索凡替尼； 10.患者目前存在胃及十二指肠活动性溃疡、溃疡性结肠炎等消化道疾病或未切除的肿瘤存在活动出血，或研究者判定的可能引起消化道出血、穿孔的其他状况； 11.入组前3个月内具有明显出血倾向证据或病史的患者（3个月内出血>30 mL，出现呕血、黑粪、便血）、咯血（4周内>5 mL 的新鲜血液）； 12.有显著临床意义的心血管疾病，包括但不限于入组前3个月内急性心肌梗死、严重/不稳定心绞痛或者冠脉搭桥术；充血性心力衰竭纽约心脏协会（NYHA）分级>2 级；需要药物治疗的室性心律失常；心电图检查（ECG）显示QTc间期≥480毫秒 ； 13.在过去5 年内患有其它恶性肿瘤，根治术后的皮肤基底细胞或鳞状细胞癌，或宫颈原位癌除外； 14.活动性或未能控制的严重感染（≥CTC AE 2级感染）； 15.已知的人类免疫缺陷病毒（HIV）感染；已知有临床意义的肝病病史，包括病毒性肝炎[已知为乙型肝炎病毒（HBV）携带者必须排除活动性HBV 感染，即 HBV DNA 阳性（>1×10^4拷贝/mL或者>2000 IU/ml）； 16.由于任何既往抗癌治疗引起的CTCAE 1级以上的未缓解的毒性反应，不包括脱发、淋巴细胞减少和奥沙利铂或其他药物（白蛋白结合型紫杉醇）引起的≤2级的神经毒性； 17.有症状的外周神经病变 (CTCAE≥2级)； 18.妊娠（用药前妊娠检测阳性）或正在哺乳的女性； 19.根据研究者判断，有理由怀疑患者具有不适合使用研究药物的某种疾病或状态（比如有具有癫痫发作并需要治疗），或者将会影响研究结果的解读，或者使患者处于高风险的情况。 20.尿常规提示尿蛋白≥2+，且24小时尿蛋白量>1.0g者； 21.研究治疗相关： (1)既往接受抗VEGF/VEGFR靶向药物治疗且在治疗期间出现疾病进展的患者； (2)研究治疗开始前28天内减毒活疫苗接种史或者研究期间计划行减毒活疫苗接种； (3)使用单克隆抗体后出现过重度超敏反应者； (4)研究治疗开始前2年内发生过需要全身性治疗（如使用缓解疾病药物、皮质类固醇或免疫抑制剂）的活动性自身性免疫疾病，替代疗法（例如甲状腺素、胰岛素或者用于肾上腺或垂体机能不全的生理性皮质类固醇等）除外； (5)诊断为免疫缺陷或正在接受全身性糖皮质激素治疗或任何其他形式的免疫抑制疗法。（剂量>10mg/天泼尼松或其他等疗效激素），接受激素补充疗法的患者除外； (6)有活动性结核病史者； 22.经研究者判断，患者有其他可能影响研究结果或导致本研究被迫中途终止的因素，如酗酒、药物滥用、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，会影响到患者的安全;

Exclusion criteria：

1. Received approved or ongoing systemic anti-tumor therapy and local therapy for target lesions within 4 weeks before enrollment; 2. Liver metastases accounting for 50% or more of the total liver volume determined by the investigator; 3. Biliary obstruction after clinical intervention has not been relieved or requires anti-infective treatment as judged by the investigator 14 days before the first study drug treatment; 4. Previous liver transplantation; 5. With untreated symptomatic central nervous system metastases, Patients who previously received systemic, radical treatment (radiotherapy or surgery) for brain or meningeal metastasis, and were confirmed to be stable by imaging for at least 1 month, and those who had stopped systemic hormone therapy (dose > 10 mg/day prednisone or other effective hormones) for more than 2 weeks and had no clinical symptoms were included 6. Participated in other domestic drug clinical trials that have not been approved or marketed and received the corresponding experimental drug treatment within 4 weeks before enrollment; 7. Any surgical or invasive treatment or operation (except venous catheterization, puncture drainage, biliary stent implantation for jaundice reduction therapy, etc.) within 4 weeks before the start of enrollment; 8. Patients with uncontrolled hypertension, defined as systolic blood pressure >= 140 mmHg and/or diastolic blood pressure >= 90 mmHg; 9. Patients with any disease or condition affecting drug absorption, or patients can not take oral sovatinib; 10. Patients with active gastric and duodenal ulcer, ulcerative colitis and other gastrointestinal diseases or unresected tumors with active bleeding, or other conditions that may cause gastrointestinal bleeding and perforation according to the Investigator; 11. Patients with evidence or history of significant bleeding tendency within 3 months prior to enrollment (bleeding > 30 mL, hematemesis, melena, hematochezia), hemoptysis (> 5 mL of fresh blood within 4 weeks); 12. Clinically significant cardiovascular disease, including but not limited to acute myocardial infarction, severe/unstable angina, or coronary artery bypass grafting within 3 months prior to enrollment; congestive heart failure New York Heart Association (NYHA) class > 2; ventricular arrhythmia requiring medication; QTc interval >= 480 msec on electrocardiogram (ECG); and 13. Other malignancies within the past 5 years, except for basal cell or squamous cell carcinoma of the skin after radical resection, or cervical carcinoma in situ; 14. Active or uncontrolled serious infection (>= CTC AE grade 2 infection); 15. Known human immunodeficiency virus (HIV) infection; known history of clinically significant liver disease, including viral hepatitis [known hepatitis B virus (HBV) carriers must rule out active HBV infection, i.e., HBV DNA positive (> 1 × 10^4 copies/mL or > 2000 IU/ml); 16. Unresolved toxicity of greater than CTCAE Grade 1 due to any prior anticancer treatment, excluding alopecia, lymphopenia, and neurotoxicity <= Grade 2 caused by oxaliplatin or other drugs (nab-paclitaxel); 17. Symptomatic peripheral neuropathy (CTCAE Grade >=2); 18. Pregnant (positive pregnancy test before medication) or lactating women; 19. In the judgment of the investigator, there is reason to suspect that the patient has a disease or condition (e.g., has a seizure and requires treatment) that is not suitable for the study drug, or that will affect the interpretation of the study results, or put the patient at high risk; Urine routine showed urine protein >= 2 +, and 24 hours urine protein > 1.0g; 21. Study Treatment Related: (1) Patients who previously received anti-VEGF/VEGFR-targeted drugs and experienced disease progression during treatment; (2) History of live attenuated vaccination within 28 days before the start of study treatment or planned live attenuated vaccination during the study; (3) Severe hypersensitivity reactions after the use of monoclonal antibodies; (4) Active autoimmune diseases requiring systemic treatment (such as the use of disease-modifying drugs, corticosteroids or immunosuppressive agents) within 2 years before the start of study treatment, except for replacement therapy (such as thyroxine, insulin or physiological corticosteroids for adrenal or pituitary insufficiency); (5) Diagnosis of immunodeficiency or is receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy; Dose > 10 mg/day prednisone or other equivalent effective hormones), except for patients receiving hormone supplementation therapy; (6) Have a history of active tuberculosis; 22. The investigator judges that the patient has other factors that may affect the study results or cause the study to be terminated halfway, such as alcoholism, drug abuse, other serious diseases (including mental illness) requiring concomitant treatment, serious laboratory abnormalities, accompanied by family or social factors, which will affect the safety of patients;

研究实施时间：

Study execute time：

从 From 2023-12-09 00:00:00至 To 2026-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2023-12-09 00:00:00 至 To 2025-12-31 00:00:00

干预措施：

Interventions：

组别：

研究组

样本量：

 38

Group：

study group

Sample size：

干预措施：

索凡替尼，po. qd，q3w 特瑞普利单抗，i.v. d1, q3w 化疗，根据研究者的选择

干预措施代码：

Intervention：

surufatinib, po. qd, q3w toripalimab, i.v. d1, q3w chemotherapy, as per investigator's choice

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 陕西 

市(区县)：

  

Country：

China

Province：

Shaanxi

City：

Xi'an

单位(医院)：

 西安交通大学医学院第一附属医院 

单位级别：

 三甲 

Institution
hospital：

The First Affiliated Hospital of Xi'an Jiaotong University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

无进展生存期

指标类型：

主要指标

Outcome：

progression free survival, PFS

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

客观缓解率

指标类型：

次要指标

Outcome：

objective response rate, ORR

Type：

Secondary 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, 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：

总生存期

指标类型：

次要指标

Outcome：

Overall survival, OS

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：

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：

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 80 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

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）：

2026年12月, 邮件联系研究负责人获取原始数据。

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

In December 2026, contact the research leader via email to obtain raw data.

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：

CRF

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：

  2025-03-17 16:21:20