ChiCTR2600122732 版本V1.0 版本创建时间2026/04/16 18:21:36 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：

ChiCTR2600122732 

最近更新日期：

Date of Last Refreshed on：

2026-04-16 18:21:27 

注册时间：

Date of Registration：

2026-04-16 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

PD-1/PD-L1免疫治疗联合温和冷暴露在实体瘤患者中的安全性、可行性与初步抗肿瘤活性研究

Public title：

Safety, Feasibility, and Preliminary Antitumor Activity of PD-1/PD-L1 Immunotherapy Combined with Controlled Cold Exposure in Patients with Solid Tumors

注册题目简写：

冷暴露联合ICI研究

English Acronym：

COLD-ICI

研究课题的正式科学名称：

PD-1/PD-L1免疫治疗联合温和冷暴露在实体瘤患者中的安全性、可行性与初步抗肿瘤活性研究

Scientific title：

Safety, Feasibility, and Preliminary Antitumor Activity of PD-1/PD-L1 Immunotherapy Combined with Controlled Cold Exposure in Patients with Solid Tumors

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：

李燊 

研究负责人：

马学磊 

Applicant：

Shen Li 

Study leader：

Xuelei Ma 

申请注册联系人电话：

Applicant telephone：

+86 199 8081 0727

研究负责人电话：

Study leader's telephone：

+86 134 0841 0416

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：

daniel_lishen@163.com

研究负责人电子邮件：

Study leader's E-mail：

drmaxuelei@gmail.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：

成都市外南国学巷37号

研究负责人通讯地址：

成都市外南国学巷37号

Applicant address：

No.37 Guoxue Alley, XiaoTianZhu - Wuhou District, Chengdu

Study leader's address：

No.37 Guoxue Alley, XiaoTianZhu - Wuhou District, Chengdu

申请注册联系人邮政编码：

Applicant postcode：

610041

研究负责人邮政编码：

Study leader's postcode：

610041

申请人所在单位：

四川大学华西医院

Applicant's institution：

West China Hospital, Sichuan University

研究负责人所在单位：

四川大学华西医院

Affiliation of the Leader：

West China Hospital, Sichuan University

是否获伦理委员会批准：

是/Yes

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

2025年审(2270)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：

四川大学华西医院生物医学伦理审查委员会

Name of the ethic committee：

Biomedical Ethics Review Committee of West China Hospital, Sichuan University

伦理委员会批准日期：

Date of approved by ethic committee：

2025-12-16 00:00:00

伦理委员会联系人：

邓绍林

Contact Name of the ethic committee：

Shaolin Deng

伦理委员会联系地址：

四川省成都市武侯区国学巷37号八角亭2105

Contact Address of the ethic committee：

Room 2105, Bajiaoting, No. 37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 28 8542 2654

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：

四川大学华西医院

Primary sponsor：

West China Hospital, Sichuan University

研究实施负责（组长）单位地址：

成都市外南国学巷37号

Primary sponsor's address：

No.37 Guoxue Alley, XiaoTianZhu - Wuhou District, Chengdu

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)：

Country：

China

Province：

Sichuan

City：

单位(医院)：

四川大学华西医院

具体地址：

成都市外南国学巷37号

Institution
hospital：

West China Hospital, Sichuan University

Address：

No.37 Guoxue Alley, XiaoTianZhu - Wuhou District, Chengdu

经费或物资来源：

无

Source(s) of funding：

None

Target disease：

Solid Tumor

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 I期临床试验 

Study phase：

1

研究设计：

单臂 

Study design：

Single arm 

研究目的：

1. 评估在标准PD-1/PD-L1抑制剂单药或含PD-1/PD-L1抑制剂的标准综合治疗基础上联合温和冷暴露干预的安全性、耐受性和可行性。 2. 探索联合治疗的初步抗肿瘤活性，包括不同治疗场景下的近期影像学缓解、手术相关转归及生存结局。 3. 探索冷暴露联合PD-1/PD-L1治疗对棕色脂肪组织激活、外周免疫谱、循环细胞因子、代谢组学、肠道菌群、患者报告结局及肿瘤组织免疫/代谢标志物的影响。  

Objectives of Study：

1. To evaluate the safety, tolerability, and feasibility of mild cold exposure combined with standard PD-1/PD-L1 inhibitor monotherapy or standard combination regimens containing PD-1/PD-L1 inhibitors in patients with solid tumors. 2. To explore the preliminary antitumor activity of this combined strategy, including short-term radiologic response, surgical outcomes where applicable, and survival outcomes across different treatment settings. 3. To investigate the effects of cold exposure combined with PD-1/PD-L1 therapy on brown adipose tissue activation, peripheral immune profiles, circulating cytokines, metabolomic profiles, gut microbiota, patient-reported outcomes, and changes in immune- and metabolism-related tumor tissue biomarkers when paired tissue samples are available.

药物成份或治疗方案详述：

本研究为单中心、前瞻性、单臂、开放标签I期探索性临床研究。所有受试者均在标准PD-1/PD-L1抑制剂单药或含PD-1/PD-L1抑制剂的标准综合治疗方案基础上接受可控冷暴露干预。正式干预前设置2天冷适应阶段：第-2天约20℃暴露8小时，第-1天约18℃暴露10小时。首次联合干预自第1天PD-1/PD-L1治疗同期启动，受试者于18℃恒温环境中每日08:00–20:00暴露12小时，连续7天，其余时间恢复常温环境。干预期间受试者穿轻便衣物，根据耐受情况允许使用薄毯，但不得使用主动加热设备。若后续PD-1/PD-L1治疗周期中耐受良好，可重复实施冷暴露干预。研究不改变患者既定标准抗肿瘤治疗路径。 

Description for medicine or protocol of treatment in detail：

This is a single-center, prospective, single-arm, open-label phase I exploratory clinical study. All participants will receive controlled cold exposure in addition to standard PD-1/PD-L1 inhibitor monotherapy or standard combination regimens containing PD-1/PD-L1 inhibitors. Before formal intervention, a 2-day cold adaptation phase will be implemented: approximately 20°C for 8 hours on Day -2 and approximately 18°C for 10 hours on Day -1. The first combined intervention will start on Day 1 concurrently with PD-1/PD-L1 treatment. Participants will stay in an 18°C temperature-controlled ward from 08:00 to 20:00 daily for 7 consecutive days, with return to normal ambient temperature for the remaining time. During cold exposure, participants will wear light clothing; thin blankets are allowed if needed for tolerance, but active heating devices are prohibited. If tolerated, cold exposure may be repeated in subsequent PD-1/PD-L1 treatment cycles. The study will not alter the standard antitumor treatment plan determined by the treating physician. 

纳入标准：

1. 年龄18～75岁，男女不限；预期生存期>=3个月。 2. 经病理组织学或细胞学确诊的实体恶性肿瘤患者（包括各系统实体瘤，如肺癌、乳腺癌、消化道肿瘤、泌尿生殖系统肿瘤等），肿瘤病灶可测量或可评估（需存在RECIST 1.1标准定义的可测量病灶）。 3. 病人可以是初治患者，亦可曾接受过包括PD-1/PD-L1抑制剂在内的放疗、化疗、靶向或免疫治疗，但需在试验疗法开始时不存在严重未恢复的治疗相关毒性。若既往接受过免疫检查点抑制剂治疗，需距本次入组至少4周且已从相关不良反应中恢复至<=1级。 4. 接受生理剂量全身性类固醇治疗的患者可以参加研究，但前提是类固醇剂量不超过可接受的阈值。 5. 东部肿瘤协作组（ECOG）体能状态评分0–1分（个别病例若ECOG=2，研究者判断仍可耐受试验干预者也可考虑），日常生活能够自理。 6. 重要器官功能基本正常：例如血常规检查显示中性粒细胞计数>=1.5×10^9/L，血小板>=100×10^9/L，血红蛋白>=90 g/L；生化检查显示总胆红素<=1.5倍正常上限，AST/ALT<=2.5倍正常上限（如有肝转移可放宽至5倍），血清肌酐<=1.5倍正常上限或肌酐清除率>=50 mL/min；甲状腺功能、空腹血糖等指标无未控制的明显异常（允许2型糖尿病但需血糖控制良好）。 7. 心肺功能良好：无症状性心肌缺血或严重心律失常；静息时血氧饱和度>92%；无严重慢性呼吸疾病急性加重。心功能分级NYHA I~II级。 8. 无寒冷暴露禁忌证：如未患有重度雷诺现象、寒冷性荨麻疹、寒冷球蛋白血症等对低温高度敏感性疾病；无严重心血管疾病（如近期心肌梗死、未控制的高血压或心绞痛）可能因冷暴露诱发恶化。 9. 女性受试者非妊娠或哺乳期，并在试验期间及末次给药后至少3个月内同意采取有效避孕措施；男性受试者在试验期间及末次给药3个月内也应采取避孕措施。育龄期女性入组前妊娠检测为阴性。 10. 受试者能够理解试验过程，并自愿签署书面知情同意书，愿意遵循方案完成各项检测和随访。

Inclusion criteria

1. Participants are aged 18–75 years, of either sex, with an expected survival of at least 3 months. 2. Patients must have histologically or cytologically confirmed solid malignant tumors (including, but not limited to, lung cancer, breast cancer, gastrointestinal tumors, and genitourinary tumors), with at least one measurable or evaluable lesion according to RECIST version 1.1. 3. Patients may be treatment-na?ve or previously treated with radiotherapy, chemotherapy, targeted therapy, or immunotherapy (including PD-1/PD-L1 inhibitors), provided that no severe unresolved treatment-related toxicities are present at the initiation of the study treatment; for those previously treated with immune checkpoint inhibitors, a washout period of at least 4 weeks is required prior to enrollment, and any related adverse events must have resolved to Grade ≤1. 4. Patients receiving systemic corticosteroids at physiologic doses are eligible, provided the dose does not exceed a predefined acceptable threshold. 5. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1; selected patients with ECOG 2 may be considered at the investigator’s discretion if deemed able to tolerate the study intervention, and all participants must be capable of self-care in daily life. 6. Adequate organ function is required, including hematologic parameters (absolute neutrophil count ≥1.5 × 10?/L, platelet count ≥100 × 10?/L, hemoglobin ≥90 g/L), hepatic function (total bilirubin ≤1.5 × upper limit of normal [ULN], AST/ALT ≤2.5 × ULN or ≤5 × ULN in the presence of liver metastases), renal function (serum creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/min), and no uncontrolled abnormalities in thyroid function or fasting blood glucose (patients with type 2 diabetes are allowed if well controlled). 7. Participants must have adequate cardiopulmonary function, including no symptomatic myocardial ischemia or severe arrhythmia, resting oxygen saturation >92%, no acute exacerbation of severe chronic respiratory disease, and cardiac function classified as New York Heart Association (NYHA) class I–II. 8. Participants must have no contraindications to cold exposure, including absence of severe Raynaud’s phenomenon, cold urticaria, cryoglobulinemia, or other cold-sensitive disorders, and no severe cardiovascular diseases (e.g., recent myocardial infarction, uncontrolled hypertension, or angina) that could be exacerbated by cold exposure. 9. Female participants must not be pregnant or breastfeeding and must agree to use effective contraception during the study and for at least 3 months after the last dose; male participants must also agree to use effective contraception during the study and for at least 3 months after the last dose; women of childbearing potential must have a negative pregnancy test prior to enrollment. 10. Participants must be able to understand the study procedures, voluntarily provide written informed consent, and be willing to comply with all protocol-specified assessments and follow-up.

排除标准：

1. 当前或近期（开始研究治疗前 4 周内）正在接受另一种研究药物的治疗或参与另一项研究。 2. 存在任何无法控制的活动性感染（如重度细菌、病毒或真菌感染），包括活动性肺结核；或HIV感染者。慢性乙型肝炎或丙型肝炎携带者若病毒得到控制（HBV DNA<一定拷贝数）且肝功能符合纳入要求者可入组，否则排除。 3. 已知对研究过程中可能使用的任何药物过敏的受试者。 4. 有自身免疫性疾病活动（如系统性红斑狼疮、类风湿性关节炎等）或病史，需长期使用免疫抑制剂治疗的。既往有免疫相关不良反应史（irAE）导致PD-1治疗中断的患者慎重考虑，任何先前治疗导致的未解决毒性>=CTCAE v.5.0 3级免疫毒性事件则不纳入。 5. 既往接受过PD-1/PD-L1抑制剂治疗时发生严重不良反应（如肝炎、肺炎、结肠炎、重症内分泌紊乱等>=3级）且未完全恢复或认为再暴露有高复发风险者。 6. 存在明显的心血管疾病：包括但不限于不稳定型心绞痛、严重心律失常需治疗、充血性心力衰竭（NYHA III~IV级）或左室射血分数<50%；近期（6个月内）发生过心肌梗死、中风或需介入的血栓事件。冷暴露可能诱发心血管事件，这类患者风险较高予以排除。 7. 存在中枢神经系统转移且伴有症状未受控者（如癫痫发作、颅高压等）。已接受治疗的脑转移若病情稳定且无需皮质激素可考虑纳入。 8. 严重的精神障碍或认知功能损害，无法配合完成研究流程；或合并药物滥用/酗酒等，可影响依从性的情况。 9. 任何其他研究者认为不适合参加本试验的情况。例如：未控制的糖尿病（空腹血糖持续>13.9 mmol/L）可能因冷暴露诱发波动；重度的慢性阻塞性肺疾病或哮喘在冷空气中易急性发作；或患者一般状态衰弱，无法耐受潜在风险。

Exclusion criteria：

1. Participants who are currently receiving, or have received within 4 weeks prior to the initiation of study treatment, another investigational drug or are participating in another clinical study. 2. Presence of any uncontrolled active infection, including severe bacterial, viral, or fungal infections, such as active tuberculosis, or known HIV infection; patients with chronic hepatitis B or hepatitis C infection may be eligible if viral load is adequately controlled (e.g., HBV DNA below a predefined threshold) and liver function meets the inclusion criteria; otherwise, they will be excluded. 3. Known hypersensitivity or allergy to any medications that may be used during the study. 4. Active autoimmune disease (e.g., systemic lupus erythematosus, rheumatoid arthritis) or a history of autoimmune disease requiring long-term immunosuppressive therapy; patients with a history of immune-related adverse events (irAEs) leading to discontinuation of PD-1 therapy should be carefully evaluated; any unresolved toxicity from prior treatment of Grade >=3 immune-related adverse events according to CTCAE version 5.0 will lead to exclusion. 5. History of severe adverse events (e.g., hepatitis, pneumonitis, colitis, or severe endocrine disorders of Grade >=3) during prior PD-1/PD-L1 inhibitor therapy that have not fully resolved or are considered to have a high risk of recurrence upon re-exposure. 6. Significant cardiovascular disease, including but not limited to unstable angina, clinically significant arrhythmias requiring treatment, congestive heart failure (New York Heart Association [NYHA] class III–IV), or left ventricular ejection fraction <50%; history of myocardial infarction, stroke, or thromboembolic events requiring intervention within the past 6 months; given that cold exposure may precipitate cardiovascular events, such patients are considered at high risk and will be excluded. 7. Presence of symptomatic and uncontrolled central nervous system metastases (e.g., seizures, increased intracranial pressure); patients with previously treated brain metastases may be eligible if the condition is stable and does not require corticosteroid therapy. 8. Severe psychiatric disorders or cognitive impairment that may preclude compliance with study procedures, or conditions such as substance abuse or alcoholism that may affect adherence. 9. Any other condition that, in the investigator's judgment, would make the participant unsuitable for the study; for example, uncontrolled diabetes (e.g., persistent fasting blood glucose >13.9 mmol/L) that may be exacerbated by cold exposure, severe chronic obstructive pulmonary disease or asthma prone to acute exacerbations in cold environments, or generally poor physical condition rendering the patient unable to tolerate potential risks.

研究实施时间：

Study execute time：

从 From 2026-04-15 00:00:00至 To 2029-06-30 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2026-04-20 00:00:00 至 To 2027-03-31 00:00:00  

干预措施：

Interventions：

组别：

温和冷暴露联合PD-1/PD-L1标准治疗组

样本量：

24

Group：

Mild Cold Exposure Plus Standard PD-1/PD-L1 Therapy Arm

Sample size：

干预措施：

标准PD-1/PD-L1抑制剂单药或含PD-1/PD-L1抑制剂的标准综合治疗；18℃可控温和冷暴露干预

干预措施代码：

Intervention：

Standard PD-1/PD-L1 inhibitor monotherapy or standard combination regimens containing PD-1/PD-L1 inhibitors; Controlled mild cold exposure at 18°C

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)：

 成都市 

Country：

China 

Province：

Sichuan 

City：

Chengdu 

单位(医院)：

四川大学华西医院 

单位级别：

三甲 

Institution
hospital：

West China Hospital, Sichuan University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

安全性与可行性

指标类型：

主要指标

Outcome：

Safety and Feasibility

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：

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：

总生存期

指标类型：

次要指标

Outcome：

Overall Survival, OS

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

棕色脂肪组织激活状态

指标类型：

次要指标

Outcome：

Brown Adipose Tissue Activation

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

外周免疫谱及循环细胞因子变化

指标类型：

次要指标

Outcome：

Peripheral Immune Profile and Circulating Cytokine Changes

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

代谢组学变化

指标类型：

次要指标

Outcome：

Metabolomic Changes

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

肠道菌群变化

指标类型：

次要指标

Outcome：

Gut Microbiota Changes

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

患者报告结局

指标类型：

次要指标

Outcome：

Patient-Reported Outcomes

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

肿瘤组织免疫和代谢相关标志物变化

指标类型：

次要指标

Outcome：

Changes in Immune- and Metabolism-Related Tumor Tissue Biomarkers

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：

病理缓解率

指标类型：

次要指标

Outcome：

Pathological 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：

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：

外周血

Sample Name：

Blood

Tissue：

Peripheral blood

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：

粪便

组织：

消化道排泄样本

Sample Name：

Stool

Tissue：

Stool sample

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

组织：

肿瘤组织

Sample Name：

Tumor tissue

Tissue：

Tumor 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:

不公开/Private

盲法：

无

Blinding：

None

是否共享原始数据：

IPD sharing

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：

本研究采用病例报告表（CRF）和电子数据采集系统（EDC）进行数据采集与管理。所有受试者信息以唯一研究编号识别，研究数据由经授权研究人员录入、核查和维护。关键变量实行双人核对，原始资料保存于研究中心。数据库锁定前完成数据清理、质疑表回复和逻辑核查。所有研究资料严格保密，仅限授权人员访问。生物样本、影像和实验室数据与临床数据进行对应管理，并按照伦理要求和医院规范进行保存、备份和归档。

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

Study data will be collected and managed ??????? case report forms (CRFs) and an electronic data capture (EDC) system. Each participant will be identified by a unique study ID. Authorized study staff will enter, verify, and maintain the study data. Key variables will undergo dual verification, and source documents will be retained at the study center. Data cleaning, query resolution, and logic checks will be completed before database lock. All study data will be kept confidential and accessible only to authorized personnel. Biological samples, imaging data, and laboratory data will be linked to clinical data through standardized management procedures and stored, backed up, and archived in accordance with ethics requirements and institutional regulations.

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：

  2026-04-16 18:21:27