ChiCTR2500098601 版本V1.0 版本创建时间2025/03/11 11:29:53 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：

 ChiCTR2500098601 

最近更新日期：

Date of Last Refreshed on：

 2025-03-11 11:29:28 

注册时间：

Date of Registration：

 2025-03-11 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

AK112联合mFOLFOX6化疗用于新辅助治疗局部进展期直肠腺癌的单臂、单中心、探索性临床研究

Public title：

Single-arm, single-center, exploratory clinical trial of AK112 combined with mFOLFOX6 chemotherapy for neoadjuvant treatment of locally advanced rectal adenocarcinoma

注册题目简写：

English Acronym：

研究课题的正式科学名称：

AK112联合mFOLFOX6化疗用于新辅助治疗局部进展期直肠腺癌的单臂、单中心、探索性临床研究

Scientific title：

Single-arm, single-center, exploratory clinical trial of AK112 combined with mFOLFOX6 chemotherapy for neoadjuvant treatment of locally advanced rectal adenocarcinoma

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：

毕登均 

研究负责人：

任亦星 

Applicant：

Bi Dengjun 

Study leader：

Ren yixing 

申请注册联系人电话：

Applicant telephone：

 +86 182 8418 3508

研究负责人电话：

Study leader's
telephone：

+86 139 9078 3731

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：

 bidengjun@163.com

研究负责人电子邮件：

Study leader's E-mail：

 cra009@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：

四川省南充市高坪区望鹤路四段天禾嘉泰4栋901

研究负责人通讯地址：

四川省南充市顺庆区中城街道茂源南路1号

Applicant address：

901, Building 4, Tianhe Jiatai, Section 4, Wanghe Road, Gaoping District, Nanchong City, Sichuan Province 23/5000 901, Building 4, Tianhe Jiatai, Section 4, Wanghe Road, Gaoping District, Nanchong City, Sichuan Province

Study leader's address：

No. 1, Maoyuan South Road, Zhongcheng Street, Shunqing District, Nanchong City, Sichuan Province

申请注册联系人邮政编码：

Applicant postcode：

 809066471@qq.com

研究负责人邮政编码：

Study leader's postcode：

申请人所在单位：

川北医学院

Applicant's institution：

North Sichuan Medical College

研究负责人所在单位：

川北医学院附属医院

Affiliation of the Leader：

Affiliated Hospital of North Sichuan Medical College

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：

 2024ER528-1

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：

川北医学院附属医院医学伦理委员会

Name of the ethic committee：

Medical Ethics Committee of Affiliated Hospital of North Sichuan Medical College

伦理委员会批准日期：

Date of approved by ethic committee：

 2024-09-20 00:00:00

伦理委员会联系人：

杨汉丰

Contact Name of the ethic committee：

Yang Hanfeng

伦理委员会联系地址：

四川省南充市顺庆区中城街道茂源南路1号

Contact Address of the ethic committee：

No. 1, Maoyuan South Road, Zhongcheng Street, Shunqing District, Nanchong City, Sichuan Province

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 817 226 2124

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：

川北医学院附属医院

Primary sponsor：

Affiliated Hospital of North Sichuan Medical College

研究实施负责（组长）单位地址：

四川省南充市顺庆区中城街道茂源南路1号

Primary sponsor's address：

No. 1, Maoyuan South Road, Zhongcheng Street, Shunqing District, Nanchong City, Sichuan Province

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

四川省

市(区县)：

南充市

Country：

China

Province：

Sichuan Province

City：

Nanchong City

单位(医院)：

川北医学院附属医院

具体地址：

四川省南充市顺庆区中城街道茂源南路1号

Institution
hospital：

Affiliated Hospital of North Sichuan Medical College

Address：

No. 1, Maoyuan South Road, Zhongcheng Street, Shunqing District, Nanchong City, Sichuan Province

经费或物资来源：

川北医学院

Source(s) of funding：

North Sichuan Medical College

研究疾病：

局部进展期直肠腺癌  

Target disease：

locally advanced rectal adenocarcinoma

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：

 探索性研究/预试验 

Study phase：

0

研究设计：

单臂 

Study design：

Single arm 

研究目的：

探索AK112联合mFOLFOX6化疗用于新辅助治疗局部进展期直肠腺癌的安全性和有效性。  

Objectives of Study：

To explore the safety and efficacy of AK112 combined with mFOLFOX6 chemotherapy for neoadjuvant treatment of locally advanced rectal adenocarcinoma.

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.签署知情同意书，自愿加入本研究； 2.组织学病理学确诊为直肠腺癌； 3.经CT和腹腔镜确定临床分期为cT4a/bN+M0（根据AJCC第8版分期）直肠腺癌； 4.既往未接受过抗肿瘤治疗； 5.计划在新辅助治疗完成后接受手术治疗； 6.年龄18-75岁，男女不限； 7.ECOG-PS评分0-1分； 8.预计生存期≥3个月； 9.育龄妇女必须在首次用药前7天内进行血清妊娠研究，且结果为阴性。育龄妇女受试者和伴侣为育龄妇女的男性受试者必须同意自签署知情同意书至末次给予研究药物后24周内避孕； 10.首剂研究药物前，实验室检查值满足以下条件： （1）血常规（筛查前 14 天内未输血、未使用造血刺激因子类药物纠正）：白细胞计数（white blood cell, WBC）≥3.0 × 10^9/L；绝对中性粒细胞计数（absolute neutrophil count, ANC）≥1.5 × 10^9/L；血小板（platelet, PLT）≥100 × 10^9/L；血红蛋白含量（hemoglobin, HGB）≥9.0 g/dL； （2）肝功能：受试者天门冬氨酸氨基转移酶（aspartate transferase, AST）≤2.5 x ULN；丙氨酸肝氨基转移酶（alanine aminotransferase, ALT）≤2.5 x ULN；血清总胆红素（total bilirubin, TBIL）≤1.5 x ULN (除外Gilbert 综合征总胆红素≤3.0 mg/dL) ； （3）肾功能：血清肌酐≤1.5 x ULN 或 肌酐清除率 (creatinine clearance rate, CrCl) ≥50 mL/minute (使用 Cockcroft/Gault 公式) ； （4）凝血功能：国际标准化比率（international normalized ratio, INR）≤1.5 x ULN，活化部分凝血活酶时间（activated partial thromboplastin time, APTT）≤1.5 x ULN（仅适用于目前没有接受抗凝治疗的患者，对于目前正在接受抗凝治疗的患者应接受稳定剂量的抗凝剂治疗）； （5）其他：脂肪酶≤1.5 x ULN（若脂肪酶>1.5 x ULN无临床或影像学证实胰腺炎的情况可以入组）；淀粉酶 ≤1.5 x ULN（若淀粉酶>1.5 x ULN 无临床或影像学证实胰腺炎的情况可以入组）；碱性磷酸酶（alkaline phosphatase, ALP）≤2.5ULN。

Inclusion criteria

1. Sign informed consent and join the study voluntarily; 2. Histological diagnosis of rectal adenocarcinoma; 3. CT and laparoscopy confirmed the clinical stage as cT4a/bN+M0 (according to AJCC 8th edition staging) colorectal adenocarcinoma; 4. Have not received anti-tumor therapy before; 5. Plan to undergo surgical treatment after the completion of neoadjuvant therapy; 6. Age 18-75 years old, male or female; 7. ECOG-PS score 0-1; 8. Expected survival ≥3 months; 9. Women of childbearing age must have a serum pregnancy study done within 7 days before the first medication, and the result is negative. Female subjects of reproductive age and male subjects whose partners are women of reproductive age must consent to contraception within 24 weeks from the date of signing the informed consent to the last administration of the study drug; 10. Before the first dose of the investigational drug, the laboratory test value meets the following conditions: (1) blood routine (no blood transfusion within 14 days before screening, no hematopoietic stimulating drug correction) : white blood cell count (WBC) >=3.0 × 10^9/L; absolute neutrophil count (ANC) >=1.5 × 10^9/L; platelet (PLT) >=100 × 10^9/L; hemoglobin content (hemoglobin, HGB) >=9.0 g/dL; (2) Liver function: aspartate transferase (AST) <=2.5 x ULN; alanine aminotransferase (ALT) <=2.5 x ULN; Serum total bilirubin (TBIL) <=1.5 x ULN (except Gilbert syndrome total bilirubin <=3.0 mg/dL); (3) Renal function: serum creatinine <=1.5 x ULN or creatinine clearance rate (CrCl) >=50 mL/minute (using Cockcroft/Gault formula); (4) Coagulation function: international normalized ratio (INR) <=1.5 x ULN, activated partial thromboplastin time (APTT) <=1.5 x ULN (only for patients who are not currently receiving anticoagulant therapy, patients who are currently receiving anticoagulant therapy should receive a steady dose of anticoagulant therapy); (5) Others: Lipase <=1.5 x ULN (Lipase >1.5 x ULN without clinical or imaging evidence of pancreatitis can be included in the group); Amylase <=1.5 x ULN (if amylase >1.5 x ULN has no clinical or imaging evidence of pancreatitis, it can be included in the group); alkaline phosphatase (ALP) <=2.5ULN.

排除标准：

1.首剂用药前≤5年并发其他恶性肿瘤； 2.活动性、已知或怀疑自身免疫性疾病包括但不仅限于重症肌无力、自身免疫性肝炎、系统性红斑狼疮类风湿性关节炎、炎性肠病等。 3.既往接受过任何T细胞共刺激或免疫检查点治疗，包括但不限于细胞毒性T淋巴细胞相关抗原-4（cytotoxic T lymphocyte-associated antigen-4，CTLA-4）抑制剂、PD-1抑制剂、PD-L1/2抑制剂或其他靶向T细胞的药物； 4.首剂研究药物前≤14天内使用皮质类固醇激素（＞10 mg/天强的松或等效剂量）或其他免疫抑制剂。没有活动性自身免疫疾病的情况下允许吸入或局部使用类固醇和肾上腺替代类固醇； 5.HBsAg阳性且HBV DNA拷贝数大于所在研究中心检验科正常值上限（1000拷贝数/ml或500IU/ml?），或HCV阳性（HCV RNA或HCV Ab检测提示急慢性感染）；已知HIV阳性病史或已知的获得性免疫缺陷综合征（Acquired Immune Deficiency Syndrome, AIDS）； 6.入组时存在重度感染，包括但不仅限于需住院治疗的感染并发症、菌血症、重症肺炎等； 7.在入组前28天内接受过大型手术，或计划在研究期间接受其他大型手术； 8.入组前28天内使用减毒活疫苗，或预计研究期间需要使用此种减毒活疫苗（入组前4周、治疗期间以及研究药物末次给药后5个月内患者不允许接种流感减毒活疫苗）； 9.有严重的心血管疾病，如纽约心脏病协会（New York Heart Association, NYHA）2级以上心力衰竭、不稳定型心绞痛、不稳定性心律失常、入组前3个月内发生的心肌梗死或脑血管意外； 10.既往接受过同种异体骨髓移植或实体器官移植的患者； 11.已知对研究药物或辅料过敏，已知对任何一种单抗发生严重过敏反应； 12.签署ICF前4周内曾接受其它任何试验药物治疗或参加过另一项干预性临床研究； 13.经研究者判断，受试者有其他可能导致本研究被迫中途终止的因素，如，不依从方案、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，会影响到受试者的安全，或资料及样品的收集。

Exclusion criteria：

1. Concurrent with other malignant tumors ≤5 years before the first dose; 2. Active, known or suspected autoimmune diseases include, but are not limited to, myasthenia gravis, autoimmune hepatitis, systemic lupus erythematosus rheumatoid arthritis, inflammatory bowel disease, etc. 3. Prior treatment with any T cell co-stimulation or immune checkpoint, including but not limited to cytotoxic T lymphocyte-associated antigen-4, CTLA-4) inhibitors, PD-1 inhibitors, PD-L1/2 inhibitors, or other drugs that target T cells; 4. Use of corticosteroids (> 10 mg/ day prednisone or equivalent dose) or other immunosuppressants within ≤14 days prior to the first dose of the study drug. Allowing inhaled or topical use of steroids and adrenal replacement steroids in the absence of active autoimmune disease; 5.HBsAg positive and HBV DNA copy number greater than the upper limit of normal value in the laboratory of the research center (1000 copy number /ml or 500IU/ml), or HCV positive (HCV RNA or HCV Ab test indicates acute or chronic infection); Known HIV positive history or known Acquired Immune Deficiency Syndrome (AIDS); 6. Severe infection at enrollment, including but not limited to infection complications requiring hospitalization, bacteremia, severe pneumonia, etc.; 7. Had undergone major surgery within 28 days prior to enrollment or planned to undergo other major surgery during the study period; 8. Use of live attenuated influenza vaccine within 28 days prior to enrollment, or anticipated use of such live attenuated influenza vaccine during the study period (patients are not allowed to receive live attenuated influenza vaccine 4 weeks prior to enrollment, during treatment, and within 5 months after the final administration of the study drug); 9. Severe cardiovascular disease, such as New York Heart Association (NYHA) grade 2 or higher heart failure, unstable angina, unstable arrhythmia, myocardial infarction or cerebrovascular accident within 3 months prior to enrollment; 10. Patients who have previously received allogeneic bone marrow transplantation or solid organ transplantation; 11. Known allergy to the investigational drug or excipient, known severe allergic reaction to any monoclonal antibody; 12. Received any other investigational drug treatment or participated in another interventional clinical study within 4 weeks prior to signing the ICF; 13. In the investigator's judgment, the subjects had other factors that might have led to the forced termination of the study, such as non-adherence to the protocol, other serious medical conditions (including mental illness) requiring combined treatment, serious laboratory abnormalities, family or social factors that would have affected the safety of the subjects, or the collection of data and samples.

研究实施时间：

Study execute time：

从 From 2025-03-01 00:00:00至 To 2025-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2025-04-01 00:00:00 至 To 2025-12-31 00:00:00

干预措施：

Interventions：

组别：

试验组

样本量：

 40

Group：

Test group

Sample size：

干预措施：

治疗方案：AK112联合mFOLFOX6。 AK112联合mFOLFOX6方案新辅助治疗局部晚期直肠癌患者 4个周期，新辅助治疗结束后2周（±7天）进行影像学评估（RECIST 1.1 评估标准），在试验进行期间对其随访并复查相关指标。新辅助治疗有效（完全缓解或部分缓解）患者根据中心实际情况安排时间接受根治手术，新辅助治疗无效（进展或稳定）的患者，直接行同步放化疗。新辅助治疗方案：AK112 20 mg/kg每周期 第一天静脉输注 给药，Q3W，联合mFOLFOX6化疗Q3W，4周期。 手术期： 新辅助4周期治疗结束后的第1-2周内进行手术。

干预措施代码：

Intervention：

Treatment regimen: AK112 combined with mFOLFOX6. Patients with locally advanced rectal cancer were treated with AK112 combined with mFOLFOX6 neoadjuvant therapy for 4 cycles. Imaging evaluation was performed 2 weeks (+/-7 days) after the end of neoadjuvant therapy (RECIST 1.1 evaluation criteria), and relevant indicators were followed up and reviewed during the trial. Patients with effective neoadjuvant therapy (complete remission or partial remission) were scheduled to receive radical surgery according to the actual situation of the center; patients with ineffective neoadjuvant therapy (progressive or stable) were directly treated with simultaneous chemoradiotherapy. Neoadjuvant treatment regimen: AK112 20 mg/kg intravenous infusion on the first day of each cycle, Q3W, combined with mFOLFOX6 chemotherapy Q3W, 4 cycles. Operation period: Surgery was performed within 1-2 weeks after the end of 4 cycles of neoadjuvant therapy.

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 四川省 

市(区县)：

 南充市 

Country：

China

Province：

Sichuan

City：

Nanchong

单位(医院)：

 川北医学院附属医院 

单位级别：

 三甲 

Institution
hospital：

Affiliated Hospital of North Sichuan Medical College

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

病理完全缓解率（pCR）

指标类型：

主要指标

Outcome：

Pathologic complete response rate (pCR)

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

主要病理缓解（MPR）

指标类型：

次要指标

Outcome：

Major pathological response (MPR)

Type：

Secondary 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（ORR）

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：

R0切除率

指标类型：

次要指标

Outcome：

R0 resection rate

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：

标本中文名：

大便

组织：

Sample Name：

stool

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：

直肠癌组织

组织：

Sample Name：

Rectal cancer tissue

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）：

Calculated Results after
the Study Completed(upload file)：

是否共享原始数据：

IPD sharing

否No

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）：

无

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

None

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 基线评估： 人口学资料：包括姓名缩写、性别、民族、婚姻状况、出生日期、身高、体重、首次访视日期。 病史询问：既往病史及治疗史、烟酒史、药物过敏史、既往疾病或伴随疾病/症状。 生命体征：体温、血压、呼吸频率、心率。 体格检查：一般状况、皮肤粘膜、淋巴结、头颈部、胸部、腹部、肌肉骨骼、神经反射、呼吸系统、心血管系统、泌尿生殖系统、精神状况等。 实验室检查： 血常规：白细胞计数（WBC）、绝对中性粒细胞计数（ANC）、血小板计数（PLT）、血红蛋白含量（HGB）。 尿常规：尿蛋白，若尿常规显示尿蛋白++或以上，需加查24小时尿蛋白定量。 大便常规：大便性状和大便潜血。 血生化：总胆红素（TBIL）、直接胆红素（DBIL）、间接胆红素（IBIL）、谷丙转氨酶（ALT）、谷草转氨酶（AST）、碱性磷酸酶（AKP）、谷氨酰转肽酶（GGT）、乳酸脱氢酶（LDH）、总蛋白（TP）、白蛋白（ALB）、尿素氮（BUN）、肌酐（Cr）、尿酸（UA）、钾（K）、钠（Na）、氯（Cl）、钙（Ca）、磷（P）。 凝血功能：凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、凝血酶时间（TT）、纤维蛋白原（Fbg）、国际标准化比率（INR）。 甲状腺功能：血清促甲状腺激素（TSH）、游离三碘甲腺原氨酸（FT3）、游离甲状腺素（FT4）。 垂体肾上腺轴检查：促肾上腺皮质激素、皮质醇、血清皮质醇。 病毒学检查：乙肝五项、HIV抗体、HCV抗体检测。 妊娠试验：育龄女性受试者在筛选期需进行血HCG检测排除妊娠，也接受尿妊娠检测。 心电图（ECG）：注意观察QT、QTc 及P-R时间，筛选期检测3次（至少间隔10分钟），3次QTcF的平均值将作为基线QTcF。 心脏彩超：筛选期内进行1次，研究期间若出现胸前区痛、心悸等症状，可酌情加查。 肿瘤影像学检查：筛选期及术前需接受影像学评估。可根据临床指征如有需要增加脑、肝、骨、颈部、盆腔、腹腔等检查。 病理学检查：筛选期（包括签署ICF之前已完成的合格肿瘤病理学检查）及术后各检测1次。筛选期病理学检查可用三个月内的检查结果。 治疗期间评估： 生命体征：每治疗周期末访视1次、术前、手术期内进行检查。 体格检查：每治疗周期末、术前、手术期内进行检查。 合并用药/治疗：记录研究期间的合并用药/治疗信息。 心电图（ECG）：每治疗周期末、术前、手术期内进行检查，试验期如果QTc间距较基线增加＞30msec，或任意1次规定的ECG测量出现QTc间距绝对值≥450msec，则需要增加2次ECG检查（至少间隔10分钟）。 心脏彩超：研究期间若出现胸前区痛、心悸等症状，可酌情加查。 实验室检查：每治疗周期前、术前进行检查。 肿瘤标记物检测：每治疗周期末、术前进行检查。 ECOG评分：每个治疗周期的第d1±1天给药前、手术切除前7天。 治疗结束后评估： 生命体征：如果患者在研究结束前7天内未进行检查，应进行检查。 体格检查：如果患者在研究结束前7天内未进行检查，应进行检查。 合并用药/治疗：实时记录。 心电图（ECG）：如果前1治疗周期内未进行，应进行检查。 心脏彩超：如果前1治疗周期内未进行，应进行检查。 肿瘤影像学检查：如果前1治疗周期内未监测，应进行检查。 实验室检查：如果前1治疗周期内未进行，应进行检查。 妊娠试验：如果前1治疗周期内未进行，应进行检查。 肿瘤标记物检测：如果前1治疗周期内未进行，应进行检查。 ECOG评分：如果前1治疗周期内未进行，应进行检查。 不良事件随访：实时记录。 数据管理 数据记录： 病例报告表（CRF）：所有数据均需记录在CRF中，包括基线评估、治疗期间评估和治疗结束后评估的数据。 电子数据管理系统：使用电子数据管理系统（EDC）进行数据录入和管理，确保数据的准确性和完整性。 数据审核： 数据审核：定期进行数据审核，确保数据的准确性和完整性。 数据锁定：在数据收集完成后，进行数据锁定，确保数据的不可更改性。 数据安全： 数据保密：所有数据均需保密，未经授权不得泄露。 数据备份：定期进行数据备份，防止数据丢失。 数据共享： 数据共享：根据研究方案和伦理委员会的批准，决定是否共享数据。如果需要共享，将通过安全的电子数据传输方式共享数据，并签订数据使用协议。

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

Data acquisition Baseline assessment: Demographic data: includes initials, gender, ethnicity, marital status, date of birth, height, weight, date of first visit. Medical history: Previous medical history and treatment history, tobacco and alcohol history, drug allergy history, previous diseases or concomitant diseases/symptoms. Vital signs: body temperature, blood pressure, respiratory rate, heart rate. Physical examination: general condition, skin mucosa, lymph nodes, head and neck, chest, abdomen, musculoskeletal, nervous reflex, respiratory system, cardiovascular system, genitourinary system, mental condition, etc. Laboratory tests: Blood routine: White blood cell count (WBC), absolute neutrophil count (ANC), platelet count (PLT), hemoglobin content (HGB). Urine routine: urine protein. If urine routine shows urine protein ++ or above, it is necessary to check the 24-hour urine protein quantity. Stool routine: stool characteristics and stool occult blood. Blood Biochemistry: Total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), alanine aminotransferase (ALT), glutamic oxalacetic aminotransferase (AST), alkaline phosphatase (AKP), glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), total protein (TP), albumin (ALB), urea nitrogen (BUN), creatinine (Creatinine) Cr), uric acid (UA), potassium (K), sodium (Na), chlorine (Cl), calcium (Ca), phosphorus (P). Coagulation function: prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fbg), International Standardized ratio (INR). Thyroid function: Serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4). Pituitary-adrenal axis examination: corticotropin, cortisol, serum cortisol. Virological examination: Hepatitis B five items, HIV antibody, HCV antibody detection. Pregnancy test: Female subjects of childbearing age are required to undergo blood HCG testing to rule out pregnancy and urine pregnancy testing during the screening period. Electrocardiogram (ECG) : Pay attention to the QT, QTc and P-R time, three tests (at least 10 minutes apart) during the screening period, the average of the three QTcF will be used as the baseline QTcF. Heart color ultrasound: once during the screening period, if there are symptoms such as pain in the chest area and heart palpitations during the study, it can be checked as appropriate. Tumor imaging: Imaging evaluation is required during screening and before surgery. Brain, liver, bone, neck, pelvis, abdominal cavity and other examinations can be added according to clinical indications if necessary. Pathology examination: Screening period (including qualified tumor pathology examination completed before signing the ICF) and postoperative examination. Screening period pathology is available within three months of examination results. Assessment during treatment: Vital signs: 1 visit at the end of each treatment cycle, before and during surgery. Physical examination: at the end of each treatment cycle, before and during surgery. Combination medication/treatment: Information on combination medication/treatment during the study period was recorded. Electrocardiogram (ECG) : Examination at the end of each treatment cycle, before and during surgery. If the QTc interval increases > 30msec from baseline during the trial period, or if the absolute value of the QTc interval is greater than 450msec on any one of the prescribed ECG measurements, two additional ECG examinations (at least 10 minutes apart) are required. Heart color ultrasound: During the study, if there are symptoms such as pain in the chest area and heart palpitations, it can be checked as appropriate. Laboratory tests: Before and before each treatment cycle. Detection of tumor markers: at the end of each treatment cycle and before surgery. ECOG score: d1±1 day before administration and 7 days before surgical resection for each treatment cycle. Evaluation after treatment: Vital signs: Patients should be examined if they have not been examined within 7 days before the end of the study. Physical examination: Patients should be examined if they have not been examined within 7 days before the end of the study. Combination medication/treatment: real-time recording. Electrocardiogram (ECG) : If it has not been performed within the previous treatment cycle, it should be examined. Cardiac ultrasound: If not performed within the previous treatment cycle, it should be examined. Imaging of the tumor: If not monitored during the first treatment cycle, it should be examined. Laboratory tests: If not performed within the previous treatment cycle, they should be performed. Pregnancy tests: If not performed within the previous treatment cycle, they should be examined. Detection of tumor markers: If not performed within the previous treatment cycle, they should be examined. ECOG score: If not performed within the previous treatment cycle, an examination should be performed. Adverse event follow-up: real-time recording. Data management Data recording: Case Report Form (CRF) : All data should be recorded in the CRF, including baseline assessment, evaluation during treatment, and evaluation after treatment. Electronic Data Management System: Use electronic data management System (EDC) for data entry and management to ensure the accuracy and integrity of data. Data review: Data audit: Conduct data audit regularly to ensure the accuracy and completeness of data. Data locking: After data collection is complete, data locking is performed to ensure that the data cannot be modified. Data Security: Data confidentiality: All data shall be kept confidential and shall not be disclosed without authorization. Data backup: Periodically back up data to prevent data loss. Data sharing: Data sharing: Decision on whether to share data based on research protocol and ethics committee approval. If sharing is required, the data will be shared through secure electronic data transmission and a data usage agreement will be signed.

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：

  2025-03-11 11:29:28