ChiCTR2300068116 版本V1.1 版本创建时间2023/06/21 18:49:12 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：

 ChiCTR2300068116 

最近更新日期：

Date of Last Refreshed on：

 2023-02-07 17:59:47 

注册时间：

Date of Registration：

 2023-02-07 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

HAIC联合信迪利单抗和贝伐珠单抗治疗中晚期肝细胞癌的临床研究

Public title：

A clinical trial of HAIC plus sintilimab and bevacizumab as treatment for patients with advanced hepatocellular carcinoma

注册题目简写：

English Acronym：

研究课题的正式科学名称：

HAIC联合信迪利单抗和贝伐珠单抗治疗中晚期肝细胞癌的临床研究

Scientific title：

A clinical trial of HAIC plus sintilimab and bevacizumab as treatment for patients with advanced hepatocellular 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：

卢文峰 

研究负责人：

张海斌 

Applicant：

Wenfeng Lu 

Study leader：

Haibin Zhang 

申请注册联系人电话：

Applicant telephone：

 15921953910

研究负责人电话：

Study leader's
telephone：

+86 13917322068

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：

 463112126@qq.com

研究负责人电子邮件：

Study leader's E-mail：

 drzhanghb@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：

上海市杨浦区长海路225号

研究负责人通讯地址：

上海市杨浦区长海路225号

Applicant address：

225 Changhai Road, Yangpu District, Shanghai

Study leader's address：

225 Changhai Road, Yangpu District, Shanghai

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：

东方肝胆外科医院

Applicant's institution：

Eastern Hepatobiliary Surgery Hospital

研究负责人所在单位：

东方肝胆外科医院

Affiliation of the Leader：

Eastern Hepatobiliary Surgery 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：

 EHBHKY2022-H025-P001

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：

海军军医大学第三附属医院伦理委员会

Name of the ethic committee：

Ethics committee of Third Affiliated Hospital of Naval Medical University

伦理委员会批准日期：

Date of approved by ethic committee：

 2022-11-24 00:00:00

伦理委员会联系人：

邰小云

Contact Name of the ethic committee：

XiaoYun Tai

伦理委员会联系地址：

上海市杨浦区长海路225号

Contact Address of the ethic committee：

225 Changhai Road, Yangpu District, Shanghai

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 15221390719

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：

东方肝胆外科医院

Primary sponsor：

Eastern Hepatobiliary Surgery Hospital

研究实施负责（组长）单位地址：

上海市杨浦区长海路225号

Primary sponsor's address：

225 Changhai Road, Yangpu District, Shanghai

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

上海

市(区县)：

Country：

China

Province：

Shanghai

City：

单位(医院)：

东方肝胆医院

具体地址：

上海市杨浦区长海路225号

Institution
hospital：

Eastern Hepatobiliary Surgery Hospital

Address：

225 Changhai Road, Yangpu District, Shanghai

经费或物资来源：

自筹

Source(s) of funding：

self-financed

研究疾病：

肝细胞癌  

Target disease：

hepatocellular 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：

探索HIAC联合信迪利单抗和贝伐珠单抗一线治疗中晚期肝细胞癌的疗效及安全性  

Objectives of Study：

Evaluate the efficacy and safety of HIAC plus sintilimab and bevacizumab in first-line treatment of patients with advanced hepatocellular 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. 在任何试验相关流程实施之前，签署书面知情同意
2. 年龄18-70周岁
3. ECOG PS评分为0-1
4. 根据中国原发性肝癌诊疗规范（2022年版）诊断标准初次诊断为肝细胞癌
5. 巴塞罗那临床肝癌（Barcelona Clinic Liver Cancer, BCLC）分期为 B 、C期
6. 既往未接受过针对肝细胞癌的全身系统性抗肿瘤治疗
7. Child-Pugh评分A级
8. 预期生存时间>3个月；
9. 根据RECIST1.1标准至少有1个可测量病灶
10. 总三碘甲腺原氨酸（T3）或游离T3和游离甲状腺素（T4）在正常范围内。（可以接受通过甲状腺替代疗法控制）。无症状的T3，游离T3或游离T4异常的受试者可以入选
11. 充分控制血压
12. 具有充分的器官和骨髓功能，随机分组前7天内实验室检查值符合下列要求(获得实验室检查的前14天内不允许通过给予任何血液成分、细胞生长因子、白蛋白及其他纠正治疗的药物来满足条件)，具体如下：
1) 血常规：绝对中性粒细胞计数（absolute neutrophil count, ANC）≥1.5×109/L； 血小板计数（platelet, PLT）≥50×10 9/L； 血红蛋白含量（haemoglobin, HGB）≥9.0 g/dL；
2) 肝功能：血清总胆红素（total bilirubin, TBIL）≤3×正常上限（upper limit of normal value, ULN）；丙氨酸氨基转移酶（alanine aminotransferase, ALT）、天门冬氨酸氨基转移酶（aspartate transferase, AST）和碱性磷酸酶（alkaline phosphatase, ALP）≤5×ULN； 血清白蛋白≥28 g/L；
3) 肾功能：血清肌酐（creatinine, Cr）≤ 1.5×ULN 或肌酐清除率（clearance of creatinine, CCr）≥ 50mL/min（Cockcroft-Gault 公式）；尿常规结果显示尿蛋白<2+；对基线时尿常规检测显示尿蛋白≥2+的患者，应进行24小时尿液采集且24小时尿蛋白定量<1g；
4) 凝血功能：国际标准化比率（international normalized ratio， INR）和活化部分凝血活酶时间（activated partial thromboplastin time， APTT）≤ 1.5倍ULN
13. 对于育龄期女性受试者，应在接受首次研究药物给药（第1周期第1天）之前的3天内接受尿液或血清妊娠试验且结果为阴性。如果尿液妊娠试验结果无法确认为阴性，则要求进行血液妊娠试验。非育龄期女性定义为绝经后至少１年，或进行过手术绝育或子宫切除术；
14. 如存在受孕风险，所有受试者（不论男性或女性）均需在整个治疗期间直至治疗末次研究药物给药后120天（或末次化疗药物给药后180天）内采用年失败率低于1%的避孕措施。预期生存时间≥12 周

Inclusion criteria

1. Signed written informed consent prior to the implementation of any trial-related procedures
2. Aged 18-70
3. The ECOG PS score is 0-1
4. The patient was initially diagnosed with hepatocellular carcinoma according to the diagnostic criteria of China's Guidelines for the Diagnosis and Treatment of primary liver Cancer (2022 edition)
5. Barcelona Clinic Liver Cancer (BCLC) is stage B and C
6. No previous systemic antitumor therapy for hepatocellular carcinoma
7. Child-pugh Grade A
8. Expected survival time >3 months;
9. At least 1 measurable lesion according to RECIST1.1 criteria
10. Total triiodothyronine (T3) or free T3 and free thyroxine (T4) were within normal limits. (It can be controlled with thyroid replacement therapy). Subjects with asymptomatic T3, free T3, or abnormal free T4 were eligible
11. Get your blood pressure under control
12. With adequate organ and bone marrow function, laboratory test values within 7 days before randomization meet the following requirements (no blood components, cell growth factors, albumin and other corrective treatment drugs are allowed to be given within 14 days before obtaining laboratory tests), as follows:
1) Blood routine: Absolute neutrophil count (ANC) ≥1.5×109/L; Platelet count (PLT) ≥50×10 9/L; Hemoglobin (HGB) ≥9.0 g/dL;
2) Liver function: total bilirubin (TBIL) ≤3× upper limit of normal value (ULN); Alanine aminotransferase (ALT), aspartate transferase (AST) and alkaline phosphatase (ALP) ≤5×ULN; Serum albumin ≥28 g/L;
3) renal function: the serum creatinine (Cr) ≤ 1.5×ULN or the clearance of creatinine (CCr) ≥ 50mL/min (Cockcroft-gault formula); Urine routine results showed urinary protein <2+; For patients with urinary protein ≥2+ at baseline, 24-hour urine collection and 24-hour urinary protein quantification <1g should be performed.
4) Coagulation function: International Normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 times ULN
13. For female subjects of reproductive age, a negative urine or serum pregnancy test should be performed within 3 days prior to the first study drug administration (day 1 of cycle 1). If the urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is requested. Women who were not of childbearing age were defined as women who had been postmenopausal for at least 1 year or had undergone surgical sterilization or hysterectomy;
14. If there is a risk of conception, all subjects (male or female) will be required to use contraception with an annual failure rate of less than 1% for the entire treatment period until 120 days after the last study drug administration of treatment (or 180 days after the last chemotherapy drug administration). The expected survival time was ≥12 weeks

排除标准：

1. 既往经组织学/细胞学确诊的含纤维板层肝细胞癌、肉瘤样肝细胞癌、胆管癌等成分
2. 有肝性脑病病史，或有肝移植病史
3. 有临床症状需要引流的胸水、腹水、心包积液
4. 急性或者慢性活动性乙型肝炎或丙型肝炎感染者，乙型肝炎病毒（HBV） DNA＞2000IU/ml或104拷贝/ml；丙型肝炎病毒（HCV）RNA＞103拷贝/ml；乙肝表面抗原（HbsAg）与抗HCV抗体同时阳性
5. 有中枢神经系统转移
6. 既往6个月内出现过门静脉高压导致的食管或胃底静脉曲张出血事件。首次给药前3个月内已知的内镜检查存在重度（G3）静脉曲张。有门静脉高压证据（包括影像学检查发现脾大），经研究者评估出血风险高者
7. 既往3个月内发生任何危及生命的出血事件，包括需要输血治疗、手术或局部治疗、持续药物治疗
8. 既往6个月内动、静脉血栓栓塞事件，包括心肌梗死、不稳定型心绞痛、脑血管意外或一过性脑缺血发作、肺动脉栓塞、深静脉血栓或其它任何严重血栓栓塞的病史。植入式静脉输液港或导管源性血栓形成，或浅表静脉血栓形成，经过常规抗凝治疗后血栓稳定者除外。允许预防性使用小剂量低分子肝素（如依诺肝素40 mg/天）
9. 首次给药前2周内，连续10天使用阿司匹林（＞ 325 mg/天）或其他已知可以抑制血小板功能的药物如双嘧达莫或氯吡格雷等
10. 不可控制的高血压, 经最佳医学治疗后收缩压＞150mmHg或舒张压＞90 mmHg，高血压危象或高血压脑病病史
11. 症状性充血性心力衰竭（纽约心脏病协会分级II-IV级）。症状性或控制不佳的心律失常。先天性长QT综合征病史或筛查时校正的QTc＞500ms（使用Fridericia法计算）
12. 严重出血倾向或凝血功能障碍，或正在接受溶栓治疗
13. 既往6个月内有胃肠道穿孔和/或瘘管病史，肠梗阻病史（包括需要肠外营养的不完全肠梗阻），广泛肠切除（部分结肠切除或广泛小肠切除，并发慢性腹泻）、克罗恩氏病、溃疡性结肠炎或长期慢性腹泻
14. 首次给药前3周内接受过放射治疗。对于首次给药前3周前接受放射治疗的患者，必须满足下述所有条件方可入组：目前不存在任何放疗相关的毒性反应，不需要服用糖皮质激素，排除放射性肺炎、放射性肝炎、放射性肠炎等
15. 既往和目前有肺纤维化史、间质性肺炎、尘肺、药物相关肺炎、肺功能严重受损等肺部疾病
16. 活动性肺结核(TB)，正在接受抗结核治疗或者首次给药前1年内接受过抗结核治疗者
17. 人免疫缺陷病毒（HIV）感染者（HIV 1/2抗体阳性），已知的梅毒感染者
18. 处于活动期或临床控制不佳的严重感染。在首次给药前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
19. 首次给药前2年内发生过需要全身性治疗（例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。允许使用替代疗法（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）。已知的原发性免疫缺陷病史。仅存在自身免疫抗体阳性的患者需根据研究者判断确认是否存在自身免疫性疾病
20. 首次给药前4周之内使用过免疫抑制药物，不包括喷鼻、吸入性或其他途径的局部糖皮质激素或生理剂量的系统性糖皮质激素（即不超过10mg/天泼尼松或等效剂量的其他糖皮质激素）、允许因治疗哮喘、慢性阻塞性肺疾病等疾病的呼吸困难症状临时使用糖皮质激素
21. 首次给药前4周之内或计划在研究期间接受减毒活疫苗
22. 首次给药前4周之内接受过重大的外科手术（开颅、开胸或开腹手术）或者未愈合的伤口、溃疡或骨折。首次给药之前7天内接受过组织穿刺活检或其他小外科手术，以静脉输液为目的的静脉穿刺置管除外
23. 首次给药前4周之内接受过针对肝癌的局部治疗
24. 首次给药前2周内接受过具有免疫调节作用的药物（包括胸腺肽、干扰素、白介素，除外为控制胸水或腹水局部使用）
25. 不受控制/无法纠正的代谢紊乱或其它非恶性肿瘤器官疾病或全身性疾病或癌症继发反应，并可导致较高医学风险和/或生存期评价不确定性
26. 在首次给药前5年内诊断为其他恶性肿瘤，不包括经过根治的皮肤基底细胞癌、皮肤鳞状细胞癌和/或经过根治切除的原位癌。如果给药前5年以上诊断为其他恶性肿瘤或肝癌，需对复发转移病灶进行病理学或细胞学诊断
27. 既往接受过任何抗PD-1抗体、抗PD-L1/L2抗体、抗CTLA4抗体，或其他免疫治疗。既往接受过抗VEGF和/或VEGFR、RAF、MEK、PDGFR、FGFR等信号通路的靶向治疗 。
28. 已知对于任何信迪利单抗、贝伐珠单抗成分过敏；或既往对其他单克隆抗体或抗血管生成抑制剂产生过严重过敏反应
29. 首次给药前4周内接受过其他临床试验的治疗
30. 妊娠或哺乳的女性患者
31. 可能会导致以下结果的其它急性或慢性疾病、精神疾病或实验室检测值异常：增加研究参与或研究药物给药的相关风险，或者干扰研究结果的解读，而且根据研究者的判断将患者列为不符合参加本研究的资格

Exclusion criteria：

1. Previous histological/cytological diagnosis of fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma, etc
2. A history of hepatic encephalopathy or liver transplantation
3. Hydrothorax, ascites and pericardial effusion with clinical symptoms requiring drainage
4. Patients with acute or chronic active hepatitis B or C with hepatitis B virus (HBV) DNA > 2000IU/ml or 104 copies /ml; HCV RNA > 103 copies /ml; Hepatitis B surface antigen (HbsAg) and anti-HCV antibody were positive simultaneously
5. Central nervous system metastases
6. Bleeding events of oesophagal or gastric fundus varices caused by portal hypertension occurred in the previous 6 months. Severe (G3) varicose veins were known to be present on endoscopy 3 months before the first dose. Patients with evidence of portal hypertension (including splenomegaly on imaging) and a high risk of bleeding as assessed by the investigator
7. Any life-threatening bleeding event in the previous 3 months, including the need for blood transfusion therapy, surgical or local treatment, and continuous medication
8. A history of arteriovenous thromboembolic events within the previous 6 months, including myocardial infarction, unstable angina pectoris, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or any other major thromboembolism. Implantable venous port or catheter-derived thrombosis, or superficial venous thrombosis, except for thrombus stabilization after routine anticoagulant therapy. Prophylactic use of low-dose LMWH (e.g., enoxaparin 40 mg/ day) is permitted.
9. Aspirin (> 325 mg/ day) or other drugs known to inhibit platelet function, such as dipyridamole or clopidogrel, were administered for 10 consecutive days within 2 weeks before the first dose
10. Uncontrolled hypertension, systolic blood pressure > 150mmHg or diastolic blood pressure > 90 mmHg after optimal medical treatment, history of hypertensive crisis or hypertensive encephalopathy
11. Symptomatic congestive heart failure (New York Heart Association Class II-IV). Symptomatic or poorly controlled arrhythmias. History of congenital long QT syndrome or corrected QTc > 500ms at screening (calculated using Fridericia method)
12. Severe bleeding tendencies or coagulopathy, or undergoing thrombolytic therapy
13. A history of gastrointestinal perforation and/or fistula within the previous 6 months, a history of intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive bowel resection with chronic diarrhoea), Crohn's disease, ulcerative colitis, or prolonged chronic diarrhoea
14. Had received radiation therapy within 3 weeks before the first dose. Patients who received radiotherapy 3 weeks before the first dose had to meet all the following criteria to be included in the study: no current radiotherapy-related toxicity, no need for glucocorticoids, and exclusion of radiation pneumonitis, radiation hepatitis, and radiation enteritis
15. Previous or current history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, drug-related pneumonia, severe impairment of pulmonary function and other lung diseases
16. Persons with active tuberculosis (TB) who are receiving anti-TB therapy or who have received anti-TB therapy within 1 year prior to the first dose
17. People with human immunodeficiency virus (HIV 1/2 antibody positive), known to be infected with syphilis
18. Severe infections that are active or poorly controlled clinically. Severe infection within 4 weeks prior to the first dose, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
19. An active autoimmune disease requiring systemic treatment (e.g., use of disease-modifying agents, corticosteroids, or immunosuppressants) occurred in the 2 years prior to the first dose. Alternative therapies (e.g., thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) are permitted. Known history of primary immunodeficiency. Patients with only positive autoimmune antibodies should be confirmed for the autoimmune disease at the discretion of the investigator
20. Had used immunosuppressive drugs within 4 weeks before the first dose, Topical or physiological doses of systemic glucocorticoids (i.e., not exceeding 10mg/ day of prednisone or equivalent doses of other glucocorticoids) by nasal spray, inhalation, or other means are excluded, and temporary use of glucocorticoids is permitted for the treatment of dyspnea symptoms in asthma, chronic obstructive pulmonary disease, etc
21. Receive live attenuated vaccine within 4 weeks before the first dose or during the study
22. Major surgical procedures (craniotomy, thoracotomy, or laparotomy) or unhealed wounds, ulcers, or fractures had been performed within 4 weeks prior to the first dose. Tissue biopsy or other minor surgical procedures were performed within 7 days prior to the first dose, except for venipuncture catheterization for intravenous fluids
23. Received local treatment for liver cancer within 4 weeks before the first dose
24. Received immunomodulatory drugs (including thymosin, interferon, interleukin, except for topical use to control pleural effusion or ascites) within 2 weeks before the first dose.
25. Uncontrolled/uncorrectable metabolic disorders or other non-malignant organ diseases or systemic diseases or secondary reactions to cancer that may result in higher medical risks and/or uncertainty in survival evaluation
26. Other malignancies, excluding radical basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or radically resected carcinoma in situ, were diagnosed within 5 years before the first dose. If other malignancies or liver cancer were diagnosed more than 5 years before administration, pathological or cytological diagnosis of recurrent and metastatic lesions should be performed
27. Previous treatment with any anti-PD-1 antibody, anti-PD-L1 /L2 antibody, anti-CTLA4 antibody, or other immunotherapy. He has previously received targeted therapy against VEGF and/or VEGFR, RAF, MEK, PDGFR, FGFR and other signalling pathways.
28. Known allergy to any sintilimab or bevacizumab component; Or a previous severe allergic reaction to other monoclonal antibodies or antiangiogenic inhibitors
29. Treatment received in other clinical trials within 4 weeks prior to the first dose
30. Female patients who are pregnant or breastfeeding
31. Other acute or chronic diseases, psychiatric disorders, or abnormal laboratory test values that could increase the risk associated with study participation or study drug administration, interfere with the interpretation of study results, and classify patients as ineligible for study participation at the investigator's discretion

研究实施时间：

Study execute time：

从 From 2023-02-06 00:00:00至 To 2026-03-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2023-02-13 00:00:00 至 To 2024-03-31 00:00:00

干预措施：

Interventions：

组别：

未经治疗的中晚期肝细胞癌患者

样本量：

 46

Group：

untreated patients with advanced hepatocellular carcinoma

Sample size：

干预措施：

HAIC联合信迪利单抗和贝伐珠单抗

干预措施代码：

Intervention：

HIAC plus sintilimab and bevacizumab

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 上海 

市(区县)：

  

Country：

China

Province：

Shanghai

City：

单位(医院)：

 东方肝胆医院 

单位级别：

 三级甲等 

Institution
hospital：

Eastern Hepatobiliary Surgery Hospital

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

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

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

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

无事件生存期

指标类型：

次要指标

Outcome：

event-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：

手术转化率

指标类型：

次要指标

Outcome：

Surgical conversion rate

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

病理缓解率

指标类型：

次要指标

Outcome：

pathologic complete 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：

总生存期

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：

安全性

指标类型：

次要指标

Outcome：

safety

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

生物标志物分析

指标类型：

附加指标

Outcome：

biomarker analysis

Type：

Additional 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：

肿瘤组织

组织：

Sample Name：

tumor tissues

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：

外周血

组织：

Sample Name：

peripheral 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 70 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）：

不适用

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

NA

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：

NA

Blinding：

NA

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）：

在实验结束、论文完成并发表后，可以以电子文件的形式将原始数据在中国临床试验注册中心公开

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

After completion of this clinical trial and finish the paper publication, the data of the trial can be obtained on the web of Chinese CTR.

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：

原始数据记录及病例记录表采用excel及SPSS格式进行保存

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

All of the original data records and case records will be saved by Excel and SPSS.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2023-02-07 17:59:26