中国临床试验注册中心 - 世界卫生组织国际临床试验注册平台一级注册机构

注册号： Registration number：	ChiCTR2500111728
最近更新日期： Date of Last Refreshed on：	2025-11-05 10:31:10
注册时间： Date of Registration：	2025-11-05 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	PD-L1单抗联合新辅助放化疗治疗局部晚期直肠癌的开放标签随机对照多中心Ⅱ期临床研究
Public title：	Open-label Randomized Controlled Multicenter Phase II Clinical Study of PD-L1 Monoclonal Antibody Combined with Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer
注册题目简写：
English Acronym：
研究课题的正式科学名称：	PD-L1单抗联合新辅助放化疗治疗局部晚期直肠癌的开放标签随机对照多中心Ⅱ期临床研究
Scientific title：	Open-label Randomized Controlled Multicenter Phase II Clinical Study of PD-L1 Monoclonal Antibody Combined with Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer
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：	李宁	研究负责人：	李宁
Applicant：	Ning Li	Study leader：	Ning Li
申请注册联系人电话： Applicant telephone：	+86 135 2650 1903	研究负责人电话： Study leader's telephone：	+86 135 2650 1903
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：	lining97@126.com	研究负责人电子邮件： Study leader's E-mail：	lining97@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：	河南省郑州市东明路127号	研究负责人通讯地址：	河南省郑州市东明路127号
Applicant address：	No. 127 Dongming Road, Zhengzhou City, Henan Province	Study leader's address：	No. 127 Dongming Road, Zhengzhou City, Henan Province
申请注册联系人邮政编码： Applicant postcode：	450000	研究负责人邮政编码： Study leader's postcode：	450000
申请人所在单位：	郑州大学附属肿瘤医院
Applicant's institution：	Zhengzhou University Affiliated Cancer Hospital
研究负责人所在单位：	郑州大学附属肿瘤医院
Affiliation of the Leader：	Zhengzhou University Affiliated Cancer 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：	2025-480-002	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：	河南省肿瘤医院医学伦理委员会
Name of the ethic committee：	Medical Ethics Committee of Henan Cancer Hospital
伦理委员会批准日期： Date of approved by ethic committee：	2025-10-13 00:00:00
伦理委员会联系人：	丁晶
Contact Name of the ethic committee：	Jing Ding
伦理委员会联系地址：	No. 127 Dongming Road, Zhengzhou City, Henan Province
Contact Address of the ethic committee：	Zhengzhou University Affiliated Cancer Hospital
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 371 6558 8251	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：

郑州大学附属肿瘤医院

Primary sponsor：

Zhengzhou University Affiliated Cancer Hospital

研究实施负责（组长）单位地址：

河南省郑州市东明路127号

Primary sponsor's address：

No. 127 Dongming Road, Zhengzhou City, Henan 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)：	河南	市(区县)：
Country：	China	Province：	Henan	City：
单位(医院)：	郑州大学附属肿瘤医院	具体地址：	河南省郑州市东明路127号
Institution hospital：	Zhengzhou University Affiliated Cancer Hospital	Address：	No. 127 Dongming Road, Zhengzhou City, Henan Province

经费或物资来源：

无

Source(s) of funding：

None

研究疾病：

直肠癌

Target disease：

Rectal cancer

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：

随机平行对照

Study design：

Parallel

研究目的：

评价PD-L1单抗联合新辅助放化疗治疗局部晚期直肠癌的开放标签随机对照多中心Ⅱ期临床研究的有效性和安全性。

Objectives of Study：

Evaluate the efficacy and safety of an open label randomized controlled multicenter phase II clinical trial of PD-L1 monoclonal antibody combined with neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

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)	自愿签署本研究的知情同意书；
2)	18-75岁的男性或女性患者；
3)	经病理学（组织学或细胞学）检查证实是局部晚期直肠癌（包括粘液腺癌、印戒细胞癌等）；
4)	用促炎泛巨噬细胞亚群评分标准筛选出高评分的患者：
首先利用RNAseq技术检测患者肿瘤微环境促炎panTAMs相关基因("WARS1", "CXCL10", "CXCL9", "GBP1",  "GBP4", "GBP5", "IFIT3", "LAP3", "MX1", "PARP14", "PSMB9", "RSAD2", "SAMD9L", "STAT1", "TAP1")以及肿瘤微环境促肿瘤panTAMs相关基因("APOC1", "APOE", "CD63", "CTSB", "CTSD", "DBI", "FN1", "GSN", "LPL", "RGCC", "SDC2", "TREM2", "VIM" , "SPP1")的表达水平；随后对基因表达数据进行Z-score转化，采用RandomForestClassifier分析方法（scikit-learn 1.3.0 based on python）分别计算所述panTAMs评分（此部分计算方法目前正在申请发明专利，发明名称：免疫治疗疗效的预测装置、电子设备和存储介质，申请号：202310820632.1），得到该患者的panTAMs得分。
在大量样本结直肠癌数据集TCGA-COAD中应用上述方法计算每位患者的panTAMs得分，通过中位数（Median）确定cutoff值为2.79；
将患者的panTAMs得分与TCGA-COAD数据集的cutoff值2.79进行比较，判断患者在大量样本中的位置。如果该患者panTAMs得分大于cutoff值2.79，定义为高评分，则认为该患者潜在从免疫治疗中获益。如果该患者panTAMs得分cutoff值小于等于2.79，定义为低评分。
5)	根据RECIST1.1，至少有一个可测量病灶或可评估病灶；可测量病灶应未接受过放疗等局部治疗（肠周淋巴结影像学判断为转移，允许最短径≥10mm，也可选做靶病灶）；
6)	ECOG评分：0~1分；
7)	预期寿命≥3个月；且经过院内MDT认为需要行新辅助治疗（或中低位直肠癌T3-4/N+M0）；
8)	器官功能充分，在筛选时要求达到以下的实验室检查值：
（1）血常规检查标准需符合：
	血红蛋白含量（HB）≥90g/L； 
	绝对中性粒细胞计数（ANC） ≥1.5×109/L；
	血小板计数（PLT） ≥100×109/L（14天内未使用白介素11或者TPO）；
（2）生化检查需符合以下标准：
	血清总胆红素（TBIL） ≤1.5倍正常值上限(ULN) ；
	ALT和AST≤2.5ULN；
	Cr≤1.5ULN或肌酐清除率(CCr)≥60ml/min，（Cockcroft-Gault公式）；
	血清白蛋白≥ 25 g/L (2.5 g/dL)
（3）多普勒超声评估：左室射血分数 (LVEF) ≥正常值低限 (50%)。
（4）凝血功能充分，定义为国际标准化比值（INR）或凝血酶原时间（PT）≤1.5倍ULN；
9)	有生育能力的女性须在研究期间、以及在最后一次给药后和化疗后至少180天这段期间采取高效的避孕措施。建议在研究药物给药前至少3个月开始采取避孕措施；未绝育的男性必须在研究期间、以及在最后一次给药后和化疗后均要求至少180天内采取高效的避孕措施。建议在研究药物给药前至少3个月开始采取避孕措施。
10)	如行输血治疗，要求输血后连续复查血常规两次，血红蛋白均≥90g/L，并排除严重消化道出血。

Inclusion criteria

1) Voluntarily sign the informed consent form for this study;
2) Male or female patients aged 18-75 years old;
3) Confirmed by pathological (histological or cytological) examination as locally advanced rectal cancer (including mucinous adenocarcinoma, signet ring cell carcinoma, etc.);
4) Screen patients with high scores using the pro-inflammatory pan macrophage subpopulation scoring criteria;
5) According to RECIST 1.1, there must be at least one measurable or assessable lesion; Measurable lesions should not have received local treatment such as radiotherapy (periintestinal lymph node imaging indicates metastasis, with a minimum allowable diameter of >=  10mm, and can also be selected as target lesions);
6) ECOG score: 0-1 points;
7) Expected lifespan >=  3 months; And according to the MDT in the hospital, neoadjuvant therapy (or T3-4/N+M0 for middle and low rectal cancer) is considered necessary;
8) The organ function is sufficient, and the following laboratory test values are required during screening:
(1) The blood routine examination standards must comply with:
Hemoglobin content (HB) >=  90g/L;  
Absolute neutrophil count (ANC) >=  1.5 × 10^9/L;
Platelet count (PLT) >=  100 × 10^9/L (no use of interleukin-11 or TPO within 14 days);
(2) Biochemical tests must meet the following standards:
Serum total bilirubin (TBIL) <=  1.5 times the upper limit of normal (ULN);
ALT and AST <=  2.5 ULN;
Cr <=  1.5 ULN or creatinine clearance rate (CCr) >=  60ml/min (Cockcroft Gault formula);
Serum albumin >=  25 g/L (2.5 g/dL)
(3) Doppler ultrasound evaluation: Left ventricular ejection fraction (LVEF) >=  lower limit of normal (50%).
(4) Adequate coagulation function, defined as International Normalized Ratio (INR) or Prothrombin Time (PT) <=  1.5 times ULN;
9) Women with fertility must take effective contraceptive measures during the study period, as well as at least 180 days after the last dose and chemotherapy. It is recommended to start using contraceptive measures at least 3 months before administering the investigational drug; Unsterilized males must take effective contraceptive measures for at least 180 days during the study period, as well as after the last dose and chemotherapy. It is recommended to start using contraceptive measures at least 3 months before administering the investigational drug.
10) If blood transfusion treatment is performed, it is required to have two consecutive blood routine tests after transfusion, with hemoglobin levels >=  90g/L, and to rule out severe gastrointestinal bleeding.

排除标准：

1) 对任何试验药物及其辅料过敏，或有严重过敏史，或为试验药物的禁忌症； 2) 有自身免疫病病史或处于活动期； 3) 有症状/无症状的脑转移； 4) 临床考虑存在严重的消化道出血（粪便潜血阳性者由研究者综合病情判断是否为严重消化道出血）； 5) 既往存在自身免疫性甲状腺炎且需要干预者； 6) 既往接受过异体骨髓移植或器官移植； 7) 先天性肺纤维化、药物导致的肺炎、机化性肺炎，或CT证实的活动性肺炎； 8) HIV检测阳性或活动性丙型肝炎（丙肝参考HCV抗体或HCV RNA）、活动期肺结核； 9) 乙肝表面抗原阳性且乙肝病毒DNA数值超过2000IU/ml； 10) 研究开始前4周内曾注射减毒活疫苗，或预期将在试验中或试验结束后5个月之内注射减毒活疫苗； 11) 既往接受过PD-1/PD-L1抗体、CTLA-4抗体，或其他针对PD-1/PD-L1和/或VEGFR抑制剂的治疗； 12) 在试验开始前2周内全身应用大剂量糖皮质激素或免疫抑制剂。 13) 有激素使用禁忌； 14) 具有影响口服药物的多种因素（比如无法吞咽、慢性腹泻和肠梗阻等）； 15) 试验开始前14天之内需要使用静脉注射抗生素的感染； 16) 慢性肠炎； 17) 存在任何重度和/未能控制的疾病的患者； 18) 长期未治愈的伤口或骨折； 19) 无法接受经外周中心静脉置管（PICC）或中心静脉置管者； 20) 在首剂研究之前4周内接受过重大外科手术（开颅、开胸或开腹手术），或预期在研究治疗期间需要接受大手术，或试验开始前4周内非诊断性的手术； 21) 入选治疗前6个月内发生过胃肠道穿孔和/或瘘管的病史；或发生过严重的动/静脉血栓事件，如脑血管意外（研究者评估的稳定型脑梗塞除外）、严重的深静脉血栓及肺栓塞者（肺栓塞事件经专科评估后仅需要行口服抗凝剂治疗患者可考虑入组）； 22) 具有临床意义的胸腹水，包括体检可发现的任何胸腹水，既往经过治疗或目前仍需治疗的胸腹水。（仅影像学显示少量胸腹水但无症状者，研究者评估不需要治疗可入选）； 23) 患有需要类固醇激素治疗的间质性肺病； 24) 不受控制的代谢紊乱或其他器官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者； 25) 显著的营养不良的患者； 26) 具有精神类药物滥用史且无法戒除或有精神障碍者； 27) 有免疫缺陷病史，包括HIV检测阳性或患有其它获得性、先天性免疫缺陷疾病，或有器官移植史者； 28) 其他原发性恶性肿瘤病史，但以下除外：1）入组前完全缓解至少2年的恶性肿瘤且在研究期间无需其他治疗；2）经充分治疗且无疾病复发证据的非黑色素瘤皮肤癌或恶性雀斑样痣；3）经充分治疗且无疾病复发证据的原位癌； 29) 妊娠或哺乳的女性患者； 30) 根据研究者的判断，有严重的危害患者安全或影响患者完成研究的伴随疾病者； 31) 经研究者判断，该患者不适合入选本研究的其他情况。

Exclusion criteria：

1) Allergy to any investigational drug or its excipients, or a history of severe allergies, or contraindications to the investigational drug; 2) Has a history of autoimmune diseases or is in an active phase; 3) Symptomatic/Asymptomatic Brain Metastasis; 4) Serious gastrointestinal bleeding is considered clinically (for patients with positive fecal occult blood, the researcher will determine whether it is severe gastrointestinal bleeding based on their overall condition); 5) Individuals with pre-existing autoimmune thyroiditis who require intervention; 6) Previously received allogeneic bone marrow transplantation or organ transplantation; 7) Congenital pulmonary fibrosis, drug-induced pneumonia, organizing pneumonia, or CT confirmed active pneumonia; 8) HIV positive or active hepatitis C (HCV antibody or HCV RNA), active tuberculosis; 9) Hepatitis B surface antigen is positive and hepatitis B virus DNA value exceeds 2000IU/ml; 10) Within 4 weeks prior to the start of the study, the individual has received a live attenuated vaccine, or is expected to receive a live attenuated vaccine during the trial or within 5 months after the trial ends; 11) Previous treatment with PD-1/PD-L1 antibodies, CTLA-4 antibodies, or other inhibitors targeting PD-1/PD-L1 and/or VEGFR; 12) Apply high-dose corticosteroids or immunosuppressants systemically within 2 weeks before the start of the experiment. 13) Contraindications for hormone use; 14) There are multiple factors that can affect oral medication, such as inability to swallow, chronic diarrhea, and intestinal obstruction; 15) Infections that require intravenous antibiotics within 14 days prior to the start of the experiment; 16) Chronic enteritis; 17) Patients with any severe and/or uncontrolled illnesses; 18) Long term untreated wounds or fractures; 19) Unable to accept peripheral central venous catheterization (PICC) or central venous catheterization; 20) Having undergone major surgical procedures (craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to the first dose of the study, or expecting to undergo major surgery during the study treatment period, or non diagnostic surgery within 4 weeks prior to the start of the trial; 21) History of gastrointestinal perforation and/or fistula occurring within the 6 months prior to enrollment for treatment; Or those who have experienced serious arterial/venous thrombotic events, such as cerebrovascular accidents (excluding stable cerebral infarction evaluated by researchers), severe deep vein thrombosis, and pulmonary embolism (patients who only require oral anticoagulant therapy after specialized evaluation of pulmonary embolism events may be considered for inclusion); 22) Clinically significant pleural and peritoneal fluid, including any pleural or peritoneal fluid that can be detected during physical examination, pleural or peritoneal fluid that has been treated in the past or still requires treatment. (Patients with only a small amount of chest and ascites on imaging but no symptoms, assessed by the researcher as not requiring treatment, may be included); 23) Suffering from interstitial lung disease that requires steroid hormone therapy; 24) Uncontrolled metabolic disorders or secondary reactions to other organ or systemic diseases or cancers that may lead to higher medical risks and/or uncertain survival evaluations; 25) Patients with significant malnutrition; 26) Individuals with a history of abuse of psychotropic drugs who are unable to quit or have mental disorders; 27) Individuals with a history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; 28) History of other primary malignant tumors, except for the following: 1) malignant tumors that have been completely relieved for at least 2 years before enrollment and do not require any other treatment during the study period; 2) Non melanoma skin cancer or malignant freckle nevi that have been adequately treated and have no evidence of disease recurrence; 3) In situ cancer with sufficient treatment and no evidence of disease recurrence; 29) Pregnant or lactating female patients; 30) According to the researcher's judgment, there are accompanying diseases that pose a serious threat to patient safety or affect the completion of the study; 31) According to the researcher's judgment, the patient is not suitable for other situations in this study.

研究实施时间：

Study execute time：

从 From 2025-11-11 00:00:00至 To 2027-11-11 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2025-11-11 00:00:00 至 To 2027-11-11 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	53
Group：	trial group	Sample size：	53
干预措施：	新辅助治疗期间联合贝莫苏拜单抗	干预措施代码：
Intervention：	Combination therapy with pembrolizumab during neoadjuvant therapy	Intervention code：

组别：	对照组	样本量：	53
Group：	control group	Sample size：	53
干预措施：	常规的新辅助治疗	干预措施代码：
Intervention：	Conventional neoadjuvant therapy	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	河南	市(区县)：
Country：	China	Province：	Henan	City：
单位(医院)：	郑州大学附属肿瘤医院	单位级别：	三甲
Institution hospital：	Zhengzhou University Affiliated Cancer Hospital	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	病理完全缓解	指标类型：	主要指标
Outcome：	Pathologic complete response	Type：	Primary indicator
测量时间点：	手术后	测量方法：
Measure time point of outcome：	After surgery	Measure method：

指标中文名：	客观缓解率（有效率）	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：

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：	肿瘤组织切片	组织：
Sample Name：	Tumor tissue section	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）：

数字表随机法

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

random number table method

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：	开放
Blinding：	Open label
试验完成后的统计结果（上传文件）：	点击下载
Calculated Results after the Study Completed(upload file)：	download

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）：	NA
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	NA
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：	NA
数据与安全监察委员会： Data and Safety Monitoring Committee：	有/Yes
注册人： Name of Registration：	2025-11-05 10:31:06