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：	ChiCTR2600126364
最近更新日期： Date of Last Refreshed on：	2026-06-08 14:58:16
注册时间： Date of Registration：	2026-06-08 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	维生素K2联合信迪利单抗及铂类化疗新辅助治疗可切除ⅡA–ⅢA期NSCLC的开放标签Ⅱ期临床研究
Public title：	An Open-Label Phase Ⅱ Clinical Study of Vitamin K2 Combined with Sintilimab and Platinum-Based Chemotherapy as Neoadjuvant Therapy for Resectable Stage ⅡA–ⅢA NSCLC
注册题目简写：
English Acronym：
研究课题的正式科学名称：	维生素K2联合信迪利单抗及铂类化疗新辅助治疗可切除ⅡA–ⅢA期NSCLC的开放标签Ⅱ期临床研究
Scientific title：	An Open-Label Phase Ⅱ Clinical Study of Vitamin K2 Combined with Sintilimab and Platinum-Based Chemotherapy as Neoadjuvant Therapy for Resectable Stage ⅡA–ⅢA NSCLC
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：	吴勤刚	研究负责人：	范军强
Applicant：	Qingang Wu	Study leader：	Junqiang Fan
申请注册联系人电话： Applicant telephone：	+86 151 6005 6825	研究负责人电话： Study leader's telephone：	+86 571 8971 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：	Qingangwu@126.com	研究负责人电子邮件： Study leader's E-mail：	zrxwk@zju.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：	浙江省杭州市上城区解放路88号	研究负责人通讯地址：	浙江省杭州市上城区解放路88号
Applicant address：	No. 88 Jiefang Road, Shangcheng District, Hangzhou City, Zhejiang Province	Study leader's address：	No. 88 Jiefang Road, Shangcheng District, Hangzhou City, Zhejiang Province
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：	浙江大学医学院附属第二医院
Applicant's institution：	The Second Affiliated Hospital Zhejiang University School of Medicine
研究负责人所在单位：	浙江大学医学院附属第二医院
Affiliation of the Leader：	The Second Affiliated Hospital Zhejiang University School of Medicine

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：	(2026)伦审研第(0872)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：	浙江大学医学院附属第二医院人体研究伦理委员会
Name of the ethic committee：	Human Research Ethics Committee of the Second Affiliated Hospital, Zhejiang University College of Medicine
伦理委员会批准日期： Date of approved by ethic committee：	2026-05-28 00:00:00
伦理委员会联系人：	吴志英
Contact Name of the ethic committee：	Zhiying Wu
伦理委员会联系地址：	浙江省杭州市解放路88号
Contact Address of the ethic committee：	No. 88 Jiefang Road, Shangcheng District, Hangzhou City, Zhejiang Province
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 571 8778 3759	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：

浙江大学医学院附属第二医院

Primary sponsor：

The Second Affiliated Hospital, Zhejiang University College of Medicine

研究实施负责（组长）单位地址：

浙江省杭州市解放路88号

Primary sponsor's address：

No. 88 Jiefang Road, Shangcheng District, Hangzhou City, Zhejiang 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)：	浙江省	市(区县)：
Country：	China	Province：	Zhejiang	City：
单位(医院)：	浙江大学医学院附属第二医院	具体地址：	浙江省杭州市解放路88号
Institution hospital：	The Second Affiliated Hospital, Zhejiang University College of Medicine	Address：	No. 88 Jiefang Road, Shangcheng District, Hangzhou City, Zhejiang Province

经费或物资来源：

自筹

Source(s) of funding：

Self-finance

研究疾病：

肺癌

Target disease：

Lung 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：

单臂

Study design：

Single arm

研究目的：

本研究旨在探索维生素K2联合信迪利单抗及铂类化疗新辅助治疗可切除ⅡA–ⅢA期非小细胞肺癌患者的可行性、安全性及有效性，并探讨其潜在的协同作用机制。

Objectives of Study：

This study aims to evaluate the feasibility, safety, and efficacy of neoadjuvant therapy combining vitamin K2 with sintilimab and platinum-based chemotherapy in patients with resectable stage IIA–IIIA non-small cell lung cancer, and to elucidate the underlying synergistic mechanisms.

药物成份或治疗方案详述：

Description for medicine or protocol of treatment in detail：

纳入标准：

Inclusion criteria

1. Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), with clinical stage IIA-IIIA according to the 8th edition of the AJCC TNM staging system, and assessed by the investigator as potentially amenable to curative surgical resection; additionally, patients with stage IIIB disease deemed potentially resectable following multidisciplinary team (MDT) evaluation.
2. At least one measurable lesion as per RECIST version 1.1.
3. Age >= 18 years; either sex.
4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
5. No prior systemic antineoplastic therapy for NSCLC.
6. Adequate organ function, defined as follows:
   (1) Hepatic function: Total bilirubin (TBIL) <= 1.5 x upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 5 x ULN.
   (2) Renal function: Urine protein < 2+ or 24-hour urine protein < 1 g, and creatinine clearance (Ccr) >= 60 mL/min calculated using the Cockcroft-Gault formula:
       Female: Ccr = (140 - age) x weight (kg) x 0.85 / [72 x serum creatinine (mg/dL)];
       Male: Ccr = (140 - age) x weight (kg) x 1.00 / [72 x serum creatinine (mg/dL)];
       Note: For patients aged >= 65 years or those with normal serum creatinine but with Ccr < 60 mL/min as calculated by the Cockcroft-Gault formula, a standard 24-hour urine collection method may be used to calculate creatinine clearance; the same calculation method must be used for the same patient during the screening period and throughout the study treatment period.
   (3) Coagulation function: International Normalized Ratio (INR) <= 1.5 or prothrombin time (PT) <= 1.5 x ULN; for patients receiving anticoagulant therapy, coagulation parameters are acceptable provided they are within the intended therapeutic range of the anticoagulant agent.
7. Life expectancy >= 12 weeks.Female patients of childbearing potential, and male patients whose partners are of childbearing potential, must use effective contraception throughout the treatment period and for 180 days after the last administration of study drug.
8. Signed written informed consent and ability to comply with protocol-specified visits and related procedures.

排除标准：

1. 研究入组前 3 周内曾参加过其他涉及试验性药物的临床研究者。 2. 既往有同种异体器官移植史者。 3. 既往有间质性肺疾病、特发性肺纤维化或肺炎史（包括药物相关性肺炎），或在筛选期胸部 CT 检查中存在活动性肺炎证据者。 4. 存在活动性或既往明确诊断的自身免疫性疾病或炎症性疾病者，包括但不限于：炎症性肠病（如溃疡性结肠炎、克罗恩病）、系统性红斑狼疮、结节病、肉芽肿性多血管炎、Graves 病、类风湿关节炎、垂体炎、葡萄膜炎等。入组前 3 个月内存在活动性憩室炎者亦予以排除。以下情况除外： (1) 仅有白癜风或脱发的患者； (2) 经激素替代治疗控制稳定的甲状腺功能减退疾病（如桥本甲状腺炎）； (3) 无需系统性治疗的慢性皮肤疾病；近 5 年内无活动性疾病表现，且经研究者评估后认为可入组的患者； (4) 仅通过饮食控制即可稳定的乳糜泻患者。 5. 存在活动性原发性免疫缺陷病史者。 6. 既往或当前存在活动性中枢神经系统转移（包括癌性脑膜炎）者。 7. 存在未得到有效控制的癫痫发作者。 8. 存在无法控制的严重合并症者，包括但不限于：症状性充血性心力衰竭、控制不佳的糖尿病或高血压、不稳定型心绞痛、未得到有效控制的心律失常、活动性间质性肺疾病、严重慢性胃肠道疾病；或存在可能影响研究依从性或知情同意能力的精神疾病或社会因素者。 9. 存在活动性感染者，包括但不限于：结核病（基于临床评估，包括病史采集、体格检查、影像学检查，并结合当地常规开展的结核病相关检测）、乙型肝炎（已知乙型肝炎表面抗原（HBsAg）阳性）、丙型肝炎，或人类免疫缺陷病毒感染（HIV-1/2 抗体阳性）。以下情况可入组： (1) 既往感染或已恢复的乙型肝炎患者，即乙型肝炎核心抗体（anti-HBc）阳性且 HBsAg 阴性； (2) 丙型肝炎抗体阳性的患者，仅当 HCV RNA 聚合酶链式反应（PCR）检测为阴性时方可入组。 10. 既往其他恶性肿瘤治疗后仍存在未恢复的不良反应（美国国立癌症研究所常见不良事件评价标准（CTCAE）>= 2 级）者，脱发、白癜风以及入组标准中已明确允许的实验室指标异常除外。对于 >= 2 级外周神经病变的患者，须经研究者评估，并在讨论后决定个案是否可入组。对于不可逆且预计不会因试验用药而进一步加重的不良反应者（如听力损失、外周神经病变等），经研究者评估后亦可考虑入组。 11. 既往接受任何免疫治疗药物期间发生过 >= 3 级免疫相关不良事件（immune-related adverse event, irAE）者，或目前仍存在未恢复至 <= 1 级的免疫相关不良事件者。 12. 已知对任何研究用药物或其任何辅料存在过敏反应或超敏反应史者。 13. 经研究者判断，不太可能遵循研究方案规定的研究流程、限制条件或相关要求的受试者，不得参与本研究。 14. 既往存在其他原发恶性肿瘤病史者，除外以下情况： (1) 既往恶性肿瘤已接受根治性治疗，且在首次给予研究用药物前 >= 3 年无已知活动性疾病证据，且复发风险较低者； (2) 已充分治疗且目前无疾病证据的非黑色素瘤皮肤癌或恶性雀斑样痣（lentigo maligna）； (3) 已充分治疗且目前无疾病证据的原位癌，包括但不限于宫颈原位癌、膀胱原位癌、已治疗的局限性前列腺癌及导管原位癌（DCIS）； (4) 惰性血液系统恶性肿瘤。 15. 在首次给予免疫检查点抑制剂前 14 天内，当前或既往使用过免疫抑制类药物者，以下情况除外： (1) 鼻用、吸入用或外用糖皮质激素； (2) 局部糖皮质激素注射（如关节腔内注射）； (3) 生理剂量的全身糖皮质激素治疗，剂量不超过泼尼松 <= 10 mg/日或等效剂量的其他糖皮质激素； (4) 作为超敏反应预处理所使用的糖皮质激素（如 CT 检查前预处理）。 16. 当前正在使用维生素 K 拮抗剂类抗凝药（如华法林）者。 17. 入组前 2 周内持续使用高剂量维生素 K 制剂/保健品且无法停用者。

Exclusion criteria：

1. Participation in any other clinical study involving investigational agents within 3 weeks prior to study enrollment. 2. History of allogeneic organ transplantation. 3. History of interstitial lung disease, idiopathic pulmonary fibrosis, or pneumonitis (including drug-related pneumonitis), or evidence of active pneumonia on chest CT at screening. 4. Active or previously diagnosed autoimmune or inflammatory disease, including but not limited to: inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease), systemic lupus erythematosus, sarcoidosis, granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc. Active diverticulitis within 3 months prior to enrollment is also excluded. The following exceptions apply: (1) Patients with vitiligo or alopecia only; (2) Hypothyroidism (e.g., Hashimoto's thyroiditis) controlled with stable hormone replacement therapy; (3) Chronic skin conditions not requiring systemic therapy; patients with no active disease manifestations within the past 5 years and deemed eligible for enrollment by the investigator; (4) Celiac disease controlled by diet alone. 5. History of active primary immunodeficiency. 6. Active or prior active central nervous system metastases (including carcinomatous meningitis). 7. Uncontrolled seizure disorder. 8. Uncontrolled severe comorbidities, including but not limited to: symptomatic congestive heart failure, uncontrolled diabetes or hypertension, unstable angina, inadequately controlled arrhythmia, active interstitial lung disease, severe chronic gastrointestinal disease; or presence of psychiatric illness or social factors that may affect study compliance or capacity to provide informed consent. 9. Active infection, including but not limited to: tuberculosis (based on clinical assessment, including medical history, physical examination, imaging studies, and locally routine tuberculosis-related testing), hepatitis B (known positive hepatitis B surface antigen [HBsAg]), hepatitis C, or human immunodeficiency virus (HIV-1/2 antibody positive). The following are eligible for enrollment: (1) Patients with prior or resolved hepatitis B infection, i.e., positive hepatitis B core antibody (anti-HBc) and negative HBsAg; (2) Patients with positive hepatitis C antibody are eligible for enrollment only if HCV RNA polymerase chain reaction (PCR) testing is negative. 10. Persistent unresolved adverse reactions (>= Grade 2 per National Cancer Institute Common Terminology Criteria for Adverse Events [CTCAE]) from prior treatment for other malignancies, except for alopecia, vitiligo, and laboratory abnormalities explicitly permitted by the inclusion criteria. Patients with >= Grade 2 peripheral neuropathy may be enrolled following investigator assessment and case-by-case discussion. Patients with irreversible adverse reactions not expected to worsen with study treatment (e.g., hearing loss, peripheral neuropathy) may also be considered for enrollment following investigator assessment. 11. History of >= Grade 3 immune-related adverse event (irAE) during prior treatment with any immunotherapeutic agent, or current presence of unresolved immune-related adverse events not recovered to <= Grade 1. 12. Known history of allergic reaction or hypersensitivity to any study drug or any of its excipients. 13. Subjects deemed by the investigator unlikely to adhere to study procedures, restrictions, or requirements specified in the study protocol. 14. History of other primary malignancies, except for the following: (1) Prior malignancy that has received curative treatment and with no known evidence of active disease for >= 3 years prior to first administration of study drug, and with low risk of recurrence; (2) Adequately treated non-melanoma skin cancer or lentigo maligna with no current evidence of disease; (3) Adequately treated in situ carcinoma with no current evidence of disease, including but not limited to cervical carcinoma in situ, bladder carcinoma in situ, treated localized prostate cancer, and ductal carcinoma in situ (DCIS); (4) Indolent hematologic malignancies. 15. Current or prior use of immunosuppressive agents within 14 days prior to first administration of immune checkpoint inhibitor, except for the following: (1) Nasal, inhaled, or topical corticosteroids; (2) Local corticosteroid injections (e.g., intra-articular injection); (3) Systemic corticosteroids at physiological doses not exceeding prednisone <= 10 mg/day or equivalent; (4) Corticosteroids used as premedication for hypersensitivity reactions (e.g., pre-treatment prior to CT examination). 16. Current use of vitamin K antagonist anticoagulants (e.g., warfarin). 17. Continuous use of high-dose vitamin K preparations/supplements within 2 weeks prior to enrollment that cannot be discontinued.

研究实施时间：

Study execute time：

从 From 2026-06-10 00:00:00至 To 2028-06-16 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2026-06-11 00:00:00 至 To 2028-06-16 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	19
Group：	Experimental Group	Sample size：	19
干预措施：	免疫治疗：信迪利单抗：200 mg，静脉输注，d1；每21天为1个周期，共3个周期。化疗：非鳞状细胞癌患者：卡铂：AUC = 5，静脉给药，d1；培美曲塞：500 mg/m2，静脉给药，d1；每21天为1个周期，共3个周期。鳞状细胞癌患者：卡铂：AUC = 5，静脉给药，d1；吉西他滨：1000 mg/m2，静脉给药，d1、d8、d15；每 21 天为 1 个周期，共3个周期。维生素K2：在新辅助免疫联合化疗期间，同步加用维生素 K2治疗。维生素 K2 采用口服给药，剂量为 45 mg/日（MK-4），自新辅助治疗第 1 周期开始，持续至新辅助治疗完成。	干预措施代码：
Intervention：	Immunotherapy: Sintilimab 200 mg, intravenous infusion, Day 1; every 21 days as one cycle, for a total of 3 cycles. Chemotherapy: Non-squamous cell carcinoma: Carboplatin AUC 5, intravenous administration, Day 1; Pemetrexed 500 mg/m2, intravenous administration, Day 1; every 21 days as one cycle, for a total of 3 cycles. Squamous cell carcinoma: Carboplatin AUC 5, intravenous administration, Day 1; Gemcitabine 1000 mg/m2, intravenous administration, Days 1, 8, and 15; every 21 days as one cycle, for a total of 3 cycles. Vitamin K2: Concurrent vitamin K2 therapy will be administered during neoadjuvant immunochemotherapy. Vitamin K2 will be given orally at a dose of 45 mg/day (MK-4), commencing from Cycle 1 of neoadjuvant therapy and continuing until completion of neoadjuvant treatment.	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	浙江	市(区县)：
Country：	china	Province：	Zhejiang	City：
单位(医院)：	浙江大学医学院附属第二医院	单位级别：	三甲
Institution hospital：	The Second Affiliated Hospital, Zhejiang University College of Medicine	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	主要病理缓解	指标类型：	主要指标
Outcome：	major pathological response,MPR	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	病理完全缓解率	指标类型：	次要指标
Outcome：	pathological complete response,pCR	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	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：	事件无进展生存期	指标类型：	次要指标
Outcome：	event-free survival,EFS	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：	肿瘤组织	组织：
Sample Name：	tumor 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		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)：

N/A

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）：	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）：	研究结束后一年内；ResMan, http://www.medresman.org.cn/login.aspx
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	Within one year after the completion of the study; ResMan, http://www.medresman.org.cn/login.aspx
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：	研究期间采集的数据将会记录在受试者个人专属的病例报告表中。每位受试者在病例报告表中被授予唯一的受试者编号用于识别。数据录入人员在病例报告表中系统中进行的任何数据修改都会通过系统的“稽查痕迹”功能自动记录。EDC外部网络访问：https://redcap.z2web1.com:10080/。试验结束6个月内上传试验数据。
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	The data collected during the research will be recorded in the individual case report forms of the subjects. Each subject is assigned a unique subject number in the case report form for identification. Any data modifications made by the data entry personnel in the case report form within the system will be automatically recorded through the "audit trail" function of the system. External network access for EDC: https://redcap.z2web1.com:10080/. The trial data will be uploaded within 6 months after the end of the trial.
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：	2026-06-08 14:58:05