ChiCTR1900027102 版本V1.0 版本创建时间2023/02/08 10:18:23 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：

ChiCTR1900027102 

最近更新日期：

Date of Last Refreshed on：

2019-10-31 22:45:23 

注册时间：

Date of Registration：

2019-10-31 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

薛军医师：该研究尚未获得伦理委员会批准。请于批准后再开始纳入参试者，并与我们联系上传批件。 卡瑞利珠单抗、甲磺酸阿帕替尼联合放射治疗一线治疗肝细胞癌合并门脉癌栓的随机、 对照、 开放、 多中 心 III 期临床研究

Public title：

A randomized, controlled, open and multicardiac phase III clinical trial of camrelizumab and apatinib mesylate combined with radiotherapy in the treatment of hepatocellular carcinoma complicated with portal vein tumor thrombus

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、甲磺酸阿帕替尼联合放射治疗一线治疗肝细胞癌合并门脉癌栓的随机、 对照、 开放、 多中 心 III 期临床研究

Scientific title：

A randomized, controlled, open and multicardiac phase III clinical trial of camrelizumab and apatinib mesylate combined with radiotherapy in the treatment of hepatocellular carcinoma complicated with portal vein tumor thrombus

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：

薛军 

研究负责人：

薛军，张涛 

Applicant：

Xue Jun 

Study leader：

Xue Jun, Zhang Tao 

申请注册联系人电话：

Applicant telephone：

+86 15071258754

研究负责人电话：

Study leader's telephone：

+86 15071258754

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：

xjunion@126.com

研究负责人电子邮件：

Study leader's E-mail：

xjunion@126.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：

湖北省武汉市解放大道127号湖北省武汉市协和医院肿瘤中心

研究负责人通讯地址：

湖北省武汉市解放大道127号

Applicant address：

1277 Jiefang Avenue, Huhan, Hubei, China

Study leader's address：

1277 Jiefang Avenue, Huhan, Hubei, 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：

华中科技大学同济医学院附属协和医院

Applicant's institution：

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

研究负责人所在单位：

湖北省武汉市协和医院肿瘤中心

Affiliation of the Leader：

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

是否获伦理委员会批准：

否/No

Approved by ethic committee：

No

伦理委员会批件文号：

Approved No. of ethic committee：

伦理委员会批件附件：

Approved file of Ethical Committee：

批准本研究的伦理委员会名称：

Name of the ethic committee：

伦理委员会批准日期：

Date of approved by ethic committee：

2013-08-26 00:00:00

伦理委员会联系人：

Contact Name of the ethic committee：

伦理委员会联系地址：

Contact Address of the ethic committee：

伦理委员会联系人电话：

Contact phone of the ethic committee：

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：

华中科技大学同济医学院附属协和医院

Primary sponsor：

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

研究实施负责（组长）单位地址：

湖北省武汉市解放大道127号

Primary sponsor's address：

1277 Jiefang Avenue, Wuhan, Hubei, 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)：

湖北

市(区县)：

武汉

Country：

China

Province：

Hubei

City：

Wuhan

单位(医院)：

华中科技大学同济医学院附属协和医院

具体地址：

解放大道127号

Institution
hospital：

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Address：

127 Jiefang Avenue

经费或物资来源：

自筹

Source(s) of funding：

Self-raised

Target disease：

hepatocellular carcinoma with portal vein tumor thrombus

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 III期临床试验 

Study phase：

3

研究设计：

随机平行对照 

Study design：

Parallel 

研究目的：

本研究拟开展卡瑞利珠单抗、甲磺酸阿帕替尼联合放射治疗肝细胞癌并 PVTT 的随机、对照、开放、多中心 III 期临床研究，期望对未来免疫治疗、靶向治疗联合放疗的新型联合治疗模式提供指导和经验，有效地提高单药治疗的抗肿瘤疗效，最终为广大患者带来更佳的生存获益。  

Objectives of Study：

In this study, we intend to carry out a randomized, controlled, open, multicenter, phase III clinical trial of camrelizumab and apatinib mesylate combined with radiotherapy in the treatment of hepatocellular carcinoma with PVTT. It is expected to provide guidance and experience for the new combination of immunotherapy and targeted therapy combined with radiotherapy in the future, effectively improve the anti-tumor efficacy of monotherapy, and ultimately bring better survival benefits for the majority of patients.

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. 患者自愿加入本研究，签署知情同意书；
2. ≥18 岁，男女皆可；
3. 经病理组织学、 细胞学或临床确诊的 HCC 患者；
4. 合并门静脉癌栓 II 或 III 型；
5. 局部治疗后进展的患者，局部治疗（包括但不限于手术、放疗、肝动脉栓塞、 TACE、肝动脉灌注、射频消融、冷冻消融或经皮乙醇注射）至少在基线影像学扫描前 4 周已完成，且局部治疗引起的毒性反应（脱发除外）必须恢复至美国国家癌症研究所-不良事件通用术语标准第 4.03 版（ NCICTCAE v4.03）评级≤1 级；
6. 既往未接受过任何针对 HCC 的系统治疗；
7. 至少有一个可测量病灶（根据 RECIST v1.1 要求，该可测量病灶螺旋 CT扫描长径≥10 mm 或肿大淋巴结短径≥15 mm；既往接受过局部治疗的病灶，根据 RECIST v1.1 标准明确进展后可作为靶病灶）；
8. Child-Pugh 肝功能分级：A 级；
9. ECOG 评分： 0～1（ECOG 评分标准）；
10. 预期生存期≥12 周；
11. 主要器官功能符合下列要求（在开始研究治疗前 7 天内）：
（1）血常规检查：（除外血红蛋白，筛查前14天内未输血、未使用粒细胞集落刺激因子 [G-CSF]、未使用药物纠正）：
中性粒细胞绝对计数≥1.5×109/L；
血小板≥75×109/L；
血红蛋白≥90 g/L；
（ 2）生化检查：（筛查前 14 天内未输白蛋白）：
血清白蛋白≥29 g/L；
血清总胆红素≤1.5×正常范围上限（ULN）；
丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）和碱性磷酸酶（AKP）≤5×ULN；
血清肌酐（Cr）≤1.5ULN 或Cr清除率>50 mL/min（Cockcroft-Gault 公式如下）
男性： Cr 清除率=((140-年龄)×体重)/(72×血 Cr)
女性： Cr 清除率=((140-年龄)×体重)/(72×血 Cr) × 0.85
体重单位： kg；血 Cr 单位： mg/mL；
（3）国际标准化比率（ INR） ≤2.3 或凝血酶原时间（ PT）超过正常对照的范围≤6 秒；
（4）尿蛋白<2+（若尿蛋白≥2+，可以进行 24 小时（ h）尿蛋白定量，24h 尿蛋白定量<1.0 g 可以入组）
12. 若患者患有活动性乙型肝炎病毒（ HBV）感染： HBV-脱氧核糖核酸（ DNA）必须＜ 500 IU/mL（若研究中心只有 copy/mL 检测单位，则必须＜ 2500copy/ml），且在研究治疗开始之前至少接受 14 天抗 HBV 治疗（依据当地标准治疗进行治疗，例如恩替卡韦）且愿意在研究期间全程接受抗病毒治疗；丙型肝炎病毒（ HCV）核糖核酸（ RNA）阳性患者必须按当地标准治疗指南接受抗病毒治疗且肝功能在 CTCAE 1 级升高以内；
13. 有生育能力的女性：必须同意从签署知情同意书开始直到研究药物末次给药后至少 120 天内禁欲（避免异性性交）或使用可靠、有效方法避孕。且在开始研究治疗前的 7 天内血清 HCG 检查必须为阴性；而且必须为非哺乳期。如果女性患者已来月经、尚未达到绝经后状态（连续无月经时间≥12 个月，除绝经之外未发现其他原因），且未接受过绝育手术（如子宫切除术、双侧输卵管结扎术或双侧卵巢切除术），则认为该患者有生育能力。
14. 对于伴侣为育龄妇女的男性患者，必须同意从签署知情同意书开始直到研究药物末次给药后至少 120 天内禁欲，或使用可靠、有效方法避孕。在同一时间段内男性患者也必须同意不捐精子。伴侣已怀孕的男性受试者须使用避孕套，无须再采用其它避孕方法。

Inclusion criteria

1. The patients volunteered to join the study and signed an informed consent form.
2. Aged >= 18 years, both male and female;
3. HCC patients diagnosed by histopathology, cytology or clinical diagnosis;
4. II or III type with portal vein tumor thrombus;
5. For patients who progressed after local treatment, local treatment (including, but not limited to, surgery, radiotherapy, hepatic artery embolization, TACE, hepatic artery perfusion, radiofrequency ablation, cryoablation, or percutaneous ethanol injection) was completed at least 4 weeks before baseline imaging scan. The toxic reactions caused by local treatment (except alopecia) must be restored to the National Cancer Institute-Standard for adverse events version 4.03 (NCICTCAE v4.03) rating <= 1;
6. No systematic treatment for HCC has been received in the past.
7. At least one measurable lesion (according to RECIST v1.1, the measurable lesion has a long diameter of more than 10 mm on spiral CT or a short diameter of enlarged lymph nodes >= 15 mm;). Lesions that have received local treatment in the past can be used as target lesions after definite progress according to RECIST v1.1 standard).
8. Child-Pugh liver function classification: grade A;
9. ECOG score: 0: 1 (ECOG scoring standard);
10. The expected survival time was >= 12 weeks.
11. The function of the main organs meets the following requirements (within 7 days prior to the commencement of the study):
(1) Blood routine examination: (except hemoglobin, no blood transfusion, no granulocyte colony stimulating factor [G-CSF], no drug correction within 14 days before screening):
The absolute count of neutrophils >= 1.5 x10^9;
Platelet >= 75 x 10^9;
Hemoglobin >= 90g;
(2) biochemical examination: (albumin was not infused within 14 days before screening):
Serum albumin >= 29g;
Upper limit of serum total bilirubin <= 1.5 x normal range (ULN);
Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (AKP) <= 5 x ULN;
Serum creatinine (Cr) <= 1.5ULN or Cr clearance > 50 mL/min (Cockcroft-Gault formula below).
Male: Cr clearance rate = (140-age) x body weight / (72 x blood Cr).
Female: Cr clearance rate = (140-age) x body weight / (72 x blood Cr) x 0.85.
Unit of body weight: kg; blood Cr unit: mg/mL;
(3) the international standardized ratio (INR) <= 2.3 or the prothrombin time (PT) exceeding the range of normal control <= 6 seconds;
(4) urinary protein < 2 + (if urinary protein >= 2, 24-hour (h) urinary protein quantification can be performed, and 24-hour urinary protein quantification < 1.0g can be entered into the group).
12. If the patient has active hepatitis B virus (HBV) infection: HBV- deoxyribonucleic acid (DNA) must be less than 500 IU/mL (if the research center has only copy/mL testing units, it must be < 2500copy/ml). And receive at least 14 days of anti-HBV therapy (according to local standards, such as entecavir) before the start of the study and are willing to receive antiviral therapy throughout the study period. Patients with hepatitis C virus (HCV) ribonucleic acid (RNA) positive must receive antiviral therapy according to the local standard treatment guidelines and the liver function is within CTCAE grade 1.
13. Fertile women: must agree to abstinence (to avoid heterosexual intercourse) or to use reliable and effective methods of contraception within at least 120 days from the signing of an informed consent form until at least 120 days after the last administration of the drug. And the serum HCG test must be negative within 7 days before the start of the study treatment, and must be non-lactation. If the female patient has menstruation and has not yet reached the postmenopausal state (continuous amenorrhea >= 12 months, no other causes are found except menopause), And has not undergone sterilization surgery (such as hysterectomy, bilateral tubal ligation or bilateral ovariectomy), the patient is considered to be fertile.
14. For male patients whose partner is a woman of childbearing age, they must agree to abstinence from signing an informed consent form until at least 120 days after the last administration of the drug, or to use reliable and effective methods of contraception. Male patients must also agree not to donate sperm during the same period of time. Male subjects with pregnant partners are required to use condoms without the need for other methods of contraception.

排除标准：

1. 已知肝胆管细胞癌、肉瘤样 HCC、混合细胞癌及纤维板层细胞癌； 5 年内或同时患有除 HCC 之外的其它活动性恶性肿瘤。已治愈的局限性肿瘤，如皮肤基底细胞癌、皮肤鳞癌、表浅膀胱癌、前列腺原位癌、宫颈原位癌、乳腺原位癌等可以入组；
2. 准备进行或者既往接受过器官或同种异基因骨髓移植的患者；
3. 有临床症状的中度、重度腹水即需要治疗性的穿刺、引流者或 Child-Pugh评分>2（仅影像学显示少量腹水但不伴有临床症状者除外）；不受控制或中等量及以上的胸腔积液、心包积液；
4. 研究治疗开始前 6 个月内有消化道出血病史或具有明确的胃肠道出血倾向，如：有出血危险的或重度食管胃底静脉曲张、有局部活动性消化道溃疡病灶、持续大便潜血阳性不可入组（基线期若大便潜血阳性，可复查，复查后若仍为阳性，需要进行胃十二指肠镜检(EGD)，若 EGD 提示出血风险的食管胃底静脉曲张则不能入组）；
5. 研究治疗开始前 6 个月内出现过腹部瘘管、胃肠道穿孔或腹腔脓肿；
6. 已知存在的遗传性或获得性出血（如凝血功能障碍）或血栓倾向，如血友病病人；目前正在或近期（研究治疗开始前 10 天内）曾出于治疗目的使用全剂量口服或注射抗凝药物或溶栓药物（允许预防性使用小剂量阿司匹林、低分子肝素）；
7. 目前正在使用或近期曾使用（研究治疗开始前 10 天内）阿司匹林（ > 325mg/天(最大抗血小板剂量）或双嘧达莫、噻氯匹定、氯吡格雷和西洛他唑治疗；
8. 研究治疗开始前 6 个月内发生过血栓形成或栓塞事件，例如脑血管意外（包括短暂性脑缺血发作、脑出血、脑梗塞）、肺栓塞等；
9. 有未能良好控制的心脏临床症状或疾病，如：（1）按照纽约心脏病协会（ NYHA）标准， II 级以上心脏功能不全或心脏彩超检查： LVEF（左室射血分数） <50%（2）不稳定型心绞痛（3）研究治疗开始前 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（5）QTc > 450ms（男性）； QTc > 470ms （女性）（ QTc 间期以 Fridericia 公式计算；若 QTc 异常，可间隔 2 分钟连续检测三次，取其平均值）；
10. 患有高血压，且经降压药物治疗无法获得良好控制（收缩压≥140 mmHg或者舒张压≥90 mmHg）（基于≥2 次测量获得的 BP 读数的平均值），允许通过使用降压治疗实现上述参数；既往曾出现高血压危象或高血压性脑病；
11. 在研究治疗开始前 6 个月内出现重大血管疾病（例如，需要手术修补或近期有外周动脉血栓形成的主动脉瘤）；
12. 严重、未愈合或裂开的伤口以及活动期溃疡或未经治疗的骨折；
13. 在研究治疗开始前 4 周内接受过大手术治疗（诊断除外）或预期需在研究期间进行大手术治疗；
14. 不能吞咽药片、吸收不良综合症或任何影响胃肠吸收的状况；
15. 在开始研究治疗之前 6 个月内曾患肠梗阻和/或曾有胃肠道梗阻临床体征或症状，包括与原有疾病有关或需要常规肠外水化、肠外营养或管饲的不完全梗阻：在初始诊断时如果有不完全梗阻/梗阻综合征/肠梗阻体征/症状的患者接受了明确（外科）治疗以消退症状时，患者或许可入组研究；
16. 有证据表明存在无法通过穿刺或近期外科手术解释说明的腹内积气；
17. 既往或目前存在中枢神经系统转移；
18. 涉及主要气道或血管的转移性疾病（比如由于肿瘤侵犯导致完全闭塞的门静脉主干或腔静脉需要排除入组，门静脉主干是指脾静脉和肠系膜上静脉的汇合处以及肝门静脉分为左右支的分支处）或位于中心的大体积纵隔肿瘤块（距隆嵴<30 mm）；
19. 有肝性脑病病史者；
20. 目前伴有间质性肺炎或间质性肺病，或既往有需激素治疗的间质性肺炎或间质性肺病病史者， 或其他可能干扰免疫相关肺毒性判断和处理的肺纤维化、机化性肺炎（例如，闭塞性细支气管炎）、尘肺、药物相关肺炎、特发性肺炎或在筛选期胸部计算机断层扫描（ CT）图上可见活动性肺炎证据或肺功能严重受损的受试者，允许放射野曾有辐射性肺炎；活动性结核；
21. 存在活动性自身免疫病或有自身免疫病病史且可能复发（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[仅通过激素替代治疗可以控制的受试者可纳入]）；受试者患有无需系统治疗的皮肤病如白癜风、银屑病、脱发，接受胰岛素治疗的经控制的 I 型糖尿病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；需要支气管扩张剂进行医学干预的哮喘患者则不能纳入；
22. 在开始研究治疗之前 14 天内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>10mg/天泼尼松或其他等效激素）；
23. 在开始研究治疗之前 14 天内使用强 CYP3A4/ CYP2C19 诱导剂包括利福平（及其类似物）和贯叶连翘或强 CYP3A4/ CYP2C19 抑制剂；
24. 已知对任何单克隆抗体、抗血管生成靶向药物有严重过敏史；
25. 在开始研究治疗之前 4 周内有重度感染，包括但不限于因感染、菌血症或重度肺炎并发症而住院治疗；在开始研究治疗之前 2 周内口服或静脉给予治疗性抗生素（接受预防性抗生素（例如，预防尿路感染或慢性阻塞性肺病加重的患者有资格参与研究）；
26. 患者先天或后天免疫功能缺陷（如 HIV 感染者）；
27. 合并乙肝及丙肝共同感染；
28. 既往曾接受过其他抗 PD-1 抗体治疗或其他针对 PD-1/PD-L1 的免疫治疗，或既往接受过阿帕替尼治疗；
29. 允许为控制症状进行的针对非靶病灶的姑息性放疗，必须在研究治疗开始使用前至少 2 周完成，放疗引起的不良事件未恢复至≤CTCAE 1 级；
30. 在开始研究治疗之前 28 天内接受过减毒活疫苗治疗，或预期于 SHR-1210治疗期间或 SHR-1210 末次给药后 60 天内需要接种此类疫苗；
31. 在开始研究治疗之前 28 天内接受过其他试验用药物治疗；
32. 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. Hepatic cholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma and fibrous lamellar cell carcinoma are known, and active malignant tumors other than HCC are found within 5 years or at the same time. Cured localized tumors, such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, prostate carcinoma in situ, cervical carcinoma in situ, breast carcinoma in situ, etc.
2. Patients who are ready to undergo or have previously received organ or allogeneic bone marrow transplantation;
3. The patients with moderate or severe ascites with clinical symptoms needed therapeutic puncture, drainage or Child-Pugh score > 2 (except for those who showed a small amount of ascites but no clinical symptoms). Uncontrolled or moderate or above pleural effusion, pericardial effusion;
4. Within 6 months before the start of the study, there was a history of gastrointestinal bleeding or a clear tendency to gastrointestinal bleeding. For example, if there is a risk of bleeding or severe esophageal and gastric varices, lesions with locally active gastrointestinal ulcers, and persistent positive fecal occult blood is not allowed in the group (if fecal occult blood is positive in the baseline period, it can be reexamined, and if it is still positive after reexamination, If gastroduodenoscopy was needed, (EGD), could not be enrolled if EGD suggested esophageal and gastric varices at risk of bleeding).
5. Abdominal fistula, gastrointestinal perforation or abdominal abscess occurred in 6 months before the beginning of the study.
6. Known hereditary or acquired bleeding (such as coagulation dysfunction) or thrombotic tendencies, such as hemophilia; Full-dose oral or injection of anticoagulant or thrombolytic drugs for therapeutic purposes (prophylactic use of low-dose aspirin, low molecular weight heparin) is currently under way or in the near future (within 10 days before the start of the study);
7. Aspirin (> 325mg/ days (maximum antiplatelet dose) or dipyridamole, ticlopidine, clopidogrel and cilostazol were currently being used or recently used (within 10 days before the start of the study) or treated with dipyridamole, ticlopidine, clopidogrel and cilostazol.
8. Thrombosis or embolism occurred within 6 months before the beginning of the study, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), pulmonary embolism and so on.
9. Having clinical symptoms or diseases of the heart that are not well controlled, such as:
(1) in accordance with (NYHA) standards of the New York Heart Association, Left ventricular ejection fraction: LVEF < 50%;
(2) unstable angina pectoris;
(3) Myocardial infarction occurred within 1 year before the beginning of treatment;
(4) clinically significant supraventricular or ventricular arrhythmias need treatment or intervention;
(5) QTc > 450ms (male); QTc > 470ms (female) (QTc interval was calculated by Fridericia formula; if QTc was abnormal, it could be detected three times at an interval of 2 minutes, and its average value could be taken).
10. Patients with hypertension, and after antihypertensive drug treatment can not be well controlled (systolic blood pressure >= 140 mmHg or diastolic blood pressure >= 90 mmHg) (based on the average of BP readings measured >= 2 times), allowing the use of antihypertensive therapy to achieve these parameters; Hypertension crisis or hypertensive encephalopathy occurred in the past.
11. Major vascular diseases occurred within 6 months of the start of the study (for example, aortic aneurysms requiring surgical repair or recent peripheral arterial thrombosis);
12. Severe, unhealed or ruptured wounds and active ulcers or untreated fractures;
13. Major surgery (except diagnosis) was performed within 4 weeks before the start of the study, or major surgery was expected to be performed during the study period.
14. Do not swallow tablets, malabsorption syndrome or any condition that affects gastrointestinal absorption;
15. He had suffered from intestinal obstruction and / or had clinical signs or symptoms of gastrointestinal obstruction within 6 months prior to the commencement of the study. Including those associated with or requiring routine extraintestinal hydration, Incomplete obstruction of parenteral nutrition or tube feeding: if, at the initial diagnosis, a patient with incomplete obstruction / obstruction syndrome / intestinal obstruction signs / symptoms has received definite (surgical) treatment to subside the symptoms, Patients may be able to join the group study;
16. There is evidence of intraabdominal gas that cannot be explained by puncture or recent surgery.
17. There is central nervous system metastasis in the past or at present.
18. Metastatic diseases involving major airways or blood vessels (such as portal vein trunk or vena cava that are completely occluded due to tumor invasion) need to be excluded from the group. The portal vein trunk refers to the confluence of the splenic vein and the superior mesenteric vein and the branch of the hepatic portal vein divided into the left and right branches) or a large mediastinal tumor mass located in the center (less than 30 mm); from the eminent ridge).
19. Patients with a history of hepatic encephalopathy;
20. Current patients with interstitial pneumonia or interstitial lung disease, or with a previous history of interstitial pneumonia or interstitial lung disease requiring hormone treatment, or other pulmonary fibrosis or organized pneumonia that may interfere with the judgment and treatment of immune-associated pulmonary toxicity (e.g., Bronchiolitis obliterans), pneumoconiosis, drug-associated pneumonia, idiopathic pneumonia or subjects with evidence of active pneumonia or severe impairment of pulmonary function on (CT) images of chest computed tomography during screening, Allow radiation fields to have radiation pneumonia; Active tuberculosis.
21. There is an active autoimmune disease or a history of autoimmune disease and may relapse (including, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, Hypothyroidism [only subjects that can be controlled by hormone replacement therapy can be included]; The subjects suffered from skin diseases such as vitiligo, psoriasis and alopecia without systematic treatment, controlled type I diabetes treated with insulin or complete remission of asthma in childhood, which could be included without any intervention in adulthood. Asthma patients who need bronchodilator for medical intervention can not be included.
22. Immunosuppressant or systemic hormone therapy was used within 14 days before the start of the study to achieve immunosuppressive purposes (dose > 10mg/ tianprednisone or other equivalent hormone).
23. Strong CYP3A4/ CYP2C19 inducers including rifampicin (and its analogues) and Hypericum perforatum or strong CYP3A4/ CYP2C19 inhibitors were used within 14 days before the start of the study.
24. It is known that there is a history of severe allergy to any monoclonal antibody or anti-angiogenic targeted drug.
25. There were severe infections within 4 weeks prior to the commencement of the study, including, but not limited to, hospitalization due to complications of infection, bacteremia or severe pneumonia. Oral or intravenous administration of therapeutic antibiotics within 2 weeks prior to the commencement of the study (receiving prophylactic antibiotics (e.g., patients who prevent urinary tract infection or exacerbation of chronic obstructive pulmonary disease are eligible to participate in the study);
26. Patients with congenital or acquired immune function deficiency (such as HIV infection);
27. Co-infection of hepatitis B and hepatitis C;
28. In the past, he has received other anti-PD-1 antibody therapy or other immunotherapy for PD-1/PD-L1, or has received apatinib treatment in the past.
29. Palliative radiotherapy for non-target lesions for symptom control must be completed at least 2 weeks before the start of the study, and the adverse events caused by radiotherapy did not recover to <= CTCAE grade 1.
30. Live attenuated vaccine was received within 28 days prior to the commencement of the study, or is expected to be vaccinated during SHR-1210 treatment or within 60 days after the last administration of SHR-1210;
31. He was treated with other experimental drugs within 28 days before the start of the study.
32. According to the researchers, patients have other factors that may affect the results of the study or lead to the forced termination of the study, such as alcohol abuse, drug abuse, and other serious illnesses (including mental illness) that require combined treatment. There are serious laboratory abnormalities, accompanied by family or social and other factors, will affect the safety of patients.

研究实施时间：

Study execute time：

从 From 2020-01-01 00:00:00至 To 2023-01-01 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2020-01-01 00:00:00 至 To 2023-01-01 00:00:00  

干预措施：

Interventions：

组别：

SBRT 组

样本量：

40

Group：

SBRT group

Sample size：

干预措施：

卡瑞利珠、 甲磺酸阿帕替尼联合 放射治疗

干预措施代码：

Intervention：

Camrelizumab, Apatinib methanesulfonate combined with radiotherapy

Intervention code：

组别：

Non-SBRT 组

样本量：

20

Group：

Non-SBRT group

Sample size：

干预措施：

卡瑞利珠联合甲磺酸阿帕替尼

干预措施代码：

Intervention：

Camrelizumab combined with apatinib mesylate

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 湖北 

市(区县)：

 武汉 

Country：

China 

Province：

Hubei 

City：

Wuhan 

单位(医院)：

华中科技大学同济医学院附属协和医院 

单位级别：

三级甲等 

Institution
hospital：

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Level of the institution：

Tertiary A Hospital

测量指标：

Outcomes：

指标中文名：

总生存期

指标类型：

主要指标

Outcome：

Over all survival (OS)

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：

无进展生存期

指标类型：

次要指标

Outcome：

Progression-free survival (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：

疾病进展时间

指标类型：

次要指标

Outcome：

Time to progression

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

缓解持续时间

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：

毒副作用

指标类型：

次要指标

Outcome：

Toxic and side effects

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：

血液

组织：

Sample Name：

Blood

Tissue：

人体标本去向

 使用后保存  

说明

Fate of sample：

Preservation after use  

Note：

标本中文名：

石蜡标本

组织：

Sample Name：

Paraffin specimen

Tissue：

人体标本去向

 使用后保存  

说明

Fate of sample：

Preservation 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）：

未说明

Randomization Procedure (please state who generates the random number sequence and by what method)：

Not stated

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：

open label

Blinding：

open label

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）：

试验完成后电子邮件获取

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

After the completion of the experiment, anyone can get through email

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：

数据采集和录入采用人工输入，excel表格

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：

Data acquisition and input using artificial input, excel 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：

  2019-10-31 22:45:23