ChiCTR2500103203 版本V1.0 版本创建时间2025/05/27 08:30:01 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：

ChiCTR2500103203 

最近更新日期：

Date of Last Refreshed on：

2025-05-27 08:29:56 

注册时间：

Date of Registration：

2025-05-27 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

一项评估晶格放疗、姑息性放疗及以PD-1/PD-L1单克隆抗体为基础的治疗在恶性实体瘤患者中安全性、耐受性及初步疗效的探索性临床研究

Public title：

An exploratory clinical trail to evaluate the safety, tolerance and preliminary efficacy of lattice radiotherapy, palliative radiotherapy and PD-1/PD-L1 monoclonal antibody based systemic therapy in patients with malignant solid tumors

注册题目简写：

English Acronym：

研究课题的正式科学名称：

一项评估晶格放疗、姑息性放疗及以PD-1/PD-L1单克隆抗体为基础的治疗在恶性实体瘤患者中安全性、耐受性及初步疗效的探索性临床研究

Scientific title：

An exploratory clinical trail to evaluate the safety, tolerance and preliminary efficacy of lattice radiotherapy, palliative radiotherapy and PD-1/PD-L1 monoclonal antibody based systemic therapy in patients with malignant 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：

余以珊 

研究负责人：

王琳琳 

Applicant：

Yishan Yu 

Study leader：

Linlin Wang 

申请注册联系人电话：

Applicant telephone：

+86 150 6401 8311

研究负责人电话：

Study leader's telephone：

+86 137 9318 7739

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：

eashion_yu@126.com

研究负责人电子邮件：

Study leader's E-mail：

wanglinlinatjn@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：

山东省济南市槐荫区济兖路440号

研究负责人通讯地址：

山东省济南市槐荫区济兖路440号

Applicant address：

440 Jiyan Road, Huaiyin District, Ji'nan, Shandong

Study leader's address：

440 Jiyan Road, Huaiyin District, Ji'nan, Shandong

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：

山东第一医科大学附属省肿瘤医院

Applicant's institution：

Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences

研究负责人所在单位：

山东第一医科大学附属省肿瘤医院

Affiliation of the Leader：

Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences

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：

SDZLEC2025-206-1

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：

山东第一医科大学附属省肿瘤医院伦理委员会

Name of the ethic committee：

Ethics Committee of Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences

伦理委员会批准日期：

Date of approved by ethic committee：

2025-04-27 00:00:00

伦理委员会联系人：

李朝伟

Contact Name of the ethic committee：

Chaowei Li

伦理委员会联系地址：

山东省济南市槐荫区济兖路440号

Contact Address of the ethic committee：

440 Jiyan Road, Huaiyin District, Jinan, Shandong

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 531 6762 6929

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：

山东第一医科大学附属省肿瘤医院

Primary sponsor：

Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences

研究实施负责（组长）单位地址：

山东省济南市槐荫区济兖路440号

Primary sponsor's address：

440 Jiyan Road, Huaiyin District, Jinan, Shandong

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

山东省

市(区县)：

Country：

China

Province：

Shandong

City：

单位(医院)：

山东第一医科大学附属省肿瘤医院

具体地址：

山东省济南市槐荫区济兖路440号

Institution
hospital：

Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences

Address：

440 Jiyan Road, Huaiyin District, Jinan, Shandong

经费或物资来源：

无

Source(s) of funding：

None

Target disease：

Malignant solid tumors

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 其它 

Study phase：

N/A

研究设计：

单臂 

Study design：

Single arm 

研究目的：

主要目的：评价晶格放疗、姑息性放疗及以PD-1/PD-L1单克隆抗体为基础的治疗在恶性实体瘤患者中的安全性、耐受性及晶格放疗顶点照射剂量限制性毒性； 次要目的：评价晶格放疗、姑息性放疗及以PD-1/PD-L1单克隆抗体为基础的治疗在恶性实体瘤患者中的初步疗效； 探索性目的：探索潜在预测疗效和安全性的生物标志物，包括但不限于肿瘤组织标本或血液样本的基因突变情况、肿瘤突变负荷（Tumor Mutational Burden，TMB）水平、细胞因子水平和免疫细胞亚群等对疗效、预后和不良反应的提示作用。  

Objectives of Study：

Main objective: To evaluate the safety, tolerability and dose-limiting toxicity of lattice radiotherapy, palliative radiotherapy and PD-1/PD-L1 monoclonal antibody-based therapy in patients with malignant solid tumors; Secondary objectives: To evaluate the preliminary efficacy of lattice radiotherapy, palliative radiotherapy, and PD-1/PD-L1 monoclonal antibody-based therapies in patients with malignant solid tumors; Exploratory Objective: To explore the potential predictive effects of biomarkers for efficacy and safety, including but not limited to gene mutations, tumor mutational burden (TMB) levels, cytokine levels, and immune cell subsets in tumor tissue specimens or blood samples, on efficacy, prognosis, and adverse reactions.

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. 年龄在18岁以上（含18岁）； 2. 经组织学或细胞学确诊、经肿瘤科医生评估存在姑息性放疗指征的实体瘤（靶病灶直径＞40mm，且体积＞50cm^3，放疗部位为脑原发肿瘤和/或脑转移瘤的患者排除）。排除研究者认为经治疗后会出现穿孔、出血、其他不可接受的风险的情况。放疗技术为IMRT及以上放疗技术。 3. 预计生存期>=12周； 4. 东部肿瘤组织协作组（ECOG）体力状态评分为0或1； 5. 主要器官功能良好，最小预期生存不小于3个月； 6. 至少有1个既往未经照射的肿瘤病灶在基线时可以准确测量，基线期直径＞40 mm且体积＞50cm^3。选择的测量方法适合准确重复测量，可以是计算机断层扫描（CT）或磁共振扫描（MRI）。 7. 育龄女性从筛选到停止研究治疗后6个月需采取合适的避孕措施且不应该哺乳。开始给药前，妊娠试验为阴性，或者满足下列标准之一证明没有妊娠风险： a. 绝经后的定义为年龄大于50岁和停止所有外源性激素替代治疗后闭经至少12个月； b. 年龄小于50岁的女性，如果停止所有外源性激素治疗后闭经12个月或以上，且促黄体激素（LH）和卵泡刺激激素（FSH）水平在实验室绝经后参考值范围内，也可认为是绝经后； c. 曾经接受不可逆的绝育手术，包括子宫切除，双侧卵巢切除或双侧输卵管切除，但双侧输卵管结扎除外； 8. 从筛选到停止研究治疗后6个月男性患者应使用屏障避孕（即避孕套）； 9. 可提供肿瘤组织/血液样本进行基因组学分析； 10. 本人自愿参加并书面签署知情同意书。

Inclusion criteria

1. Be over 18 years old (including 18 years old); 2. Solid tumors confirmed by histology or cytology and assessed by oncologists to have indications for palliative radiotherapy (target lesions with a diameter of > 40mm and a volume of >50cm^3, and patients with primary brain tumors and/or brain metastases at the site of radiotherapy are excluded). Circumcludes conditions that, in the opinion of the investigator, will have perforation, bleeding, and other unacceptable risks after treatment. Radiotherapy techniques are IMRT and above. 3. Estimated survival >=12 weeks; 4. Eastern Tumor Tissue Collaboration Group (ECOG) performance status score of 0 or 1; 5. The function of major organs is good, and the minimum expected survival is not less than 3 months; 6. At least 1 previously unirradiated tumor lesion can be accurately measured at baseline, with a diameter of >40 mm and a volume of >50cm^3 at baseline. The measurement method chosen is suitable for accurate repeat measurements, which can be computed tomography (CT) or magnetic resonance scanning (MRI). 7. Females of childbearing potential should take appropriate contraceptive measures and should not breastfeed from screening to 6 months after stopping study treatment. Have a negative pregnancy test prior to initiation of dosing, or demonstrate no risk of pregnancy if one of the following criteria is met: a. Postmenopausal is defined as being older than 50 years of age and amenorrhea for at least 12 months after cessation of all exogenous hormone replacement therapy; b. Women younger than 50 years of age who are considered postmenopausal if they have been amenorrheic for 12 months or more after stopping all exogenous hormone therapy, and the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are within the laboratory reference values for postmenopausals; c. Have undergone irreversible sterilization surgery, including hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, with the exception of bilateral tubal ligation; 8. Male patients should use barrier contraception (i.e., condoms) from screening until 6 months after discontinuation of study treatment; 9. Tumor tissue/blood samples are available for genomic analysis; 10. I voluntarily participate and sign the informed consent form in writing.

排除标准：

1.有其他恶性肿瘤（除充分治疗的非黑色素瘤皮肤癌或恶性雀斑样痣、有效治疗的原位癌或其他有效治疗的实体瘤，治疗结束后＞5年时间无疾病迹象，并且根据治疗医生的意见，无既往恶性肿瘤复发的较大风险）且在研究首次治疗后2年内需要规范治疗或大手术的患者； 2.在开始研究治疗时，有大于NCI-CTCAE 1级的未能缓解的既往治疗遗留毒性，脱发和既往化疗引起的2级神经毒性者除外； 3.首次给药前7天内，不能控制的需要频繁引流或医疗干预的浆膜腔积液（如胸腔积液、腹腔积液、心包积液等）需要在干预后 2 周内进行额外干预（不包括对渗出液行脱落细胞学检测）； 4. 经研究者判断，有任何严重或控制不良的全身性疾病，如控制不良的高血压、活动性易出血体质或活动性感染。不需要排查慢性疾病； 5.符合以下任一一项心脏检查结果： a. 静息状态下的3次心电图（ECG）检查得出的平均校正QT间期（QTc）> 470 msec，应用Fridericia公式进行QT间期校正（QTcF）； b. 静息ECG提示存在各种有临床意义的节律，传导或ECG形态学异常（例如完全性左束支传导阻滞、3度房室传导阻滞、2度房室传导阻滞和PR间期> 250 msec）； c. 存在任何增加QTc延长或心律失常事件风险的因素，如心力衰竭、低钾血症、先天性长QT综合征、长QT综合征家族史或40岁以下直系亲属的不明原因猝死或延长QT间期的任何合并药物； d.功能评估：左室射血分数（LVEF）＜50%，最近6个月内有心肌梗塞、严重或不稳定心绞痛病史或冠脉搭桥手术史或心功能不全等级≥美国纽约心脏病协会（NYHA）2级； 6. 已知既往有间质性肺病、药物性间质性肺病、需要类固醇治疗的放射性肺炎病史；或基线时有急性发作或进行性的，且研究者认为不适合入组的肺部症状或判断可能出现间质性肺病而不适合入组的高风险因素； 7. 诊断为免疫缺陷或患有活动性自身免疫性疾病（除外a.可控的I型糖尿病 b.甲状腺功能减退[仅采用激素替代疗法便可控制] c. 可控的乳糜泻 d.无需全身治疗的皮肤病[如白癜风、银屑病、脱发] e.如无外部诱因则预期不会复发的任何其他疾病）） 8.既往接受PD-1/PD-L1过程中出现过大于2级的不良反应导致停药事件的发生。 9. 骨髓储备或器官功能不足，达到下列实验室限值： a. 绝对嗜中性粒细胞计数<1.5×10^9 / L； b. 血小板计数<100×10^9 / L； c. 血红蛋白<90 g/L（<9 g/dL）； d. 丙氨酸氨基转移酶> 2.5倍的正常上限（ULN） e. 天冬氨酸氨基转氨酶> 2.5×ULN f. 总胆红素> 1.5×ULN；或存在Gilbert综合征（未结合的高胆红素血症） g. 肌酐> 1.5×ULN并且肌酐清除率<50 mL/min（通过Cockcroft - Gault公式计算）；仅当肌酐> 1.5×ULN时才需要确认肌酐清除率； 9. 筛选期存在活动性乙型肝炎（乙肝表面抗原（HBsAg）或HBcAb检测阳性，且处于乙肝活动期者（HBV-DNA ≥ 104 cps/mL或 ≥ 2000 IU/mL ））；丙型肝炎（丙肝抗体（Anti-HCV）检测阳性，且HCV RNA的PCR检测结果为阳性的受试者）；感染人免疫缺陷病毒（Human Immunodeficiency Virus ，HIV）者； 10. 首次用药前14天内，存在未控制的糖尿病或尽管进行了标准药物治疗仍存在＞1级的低钾血症、低钠血症或校正钙实验室检查值异常； 11. 哺乳期或者研究首次治疗前7天内血或尿妊娠试验结果阳性的女性； 12. 经研究者判断可能对研究的程序和要求依从性不佳（包括但不限于：受试者并发严重或不受控制的医学病症，存在潜在安全性风险，干扰研究结果的解读，影响试验依从性等情况）； 13. 研究参与者同时参与另一项临床研究，除非为观察性（非干预性） 临床研究或处于干预性研究的随访期。

Exclusion criteria：

1. Patients with other malignant tumors (except for adequately treated non-melanoma skin cancer or lentigo maligna, effectively treated carcinoma in situ or other effectively treated solid tumors, with no signs of disease within 5 years >after the end of treatment, and according to the opinion of the treating doctor, there is no greater risk of recurrence of previous malignant tumors) and require standardized treatment or major surgery within 2 years after the first treatment of the study; 2. At the time of initiation of study treatment, there are residual toxicities from previous treatment that are greater than NCI-CTCAE grade 1 that have not been relieved, except for those with alopecia and grade 2 neurotoxicity caused by previous chemotherapy; 3. Within 7 days before the first dose, uncontrollable serous effusions requiring frequent drainage or medical intervention (such as pleural effusion, peritoneal effusion, pericardial effusion, etc.) require additional intervention within 2 weeks after the intervention (excluding exfoliative cytology testing of exudate); 4. As judged by the investigator, any serious or poorly controlled systemic disease, such as poorly controlled hypertension, active bleeding constitution, or active infection. There is no need to check for chronic diseases; 5. Match any of the following cardiac test results: a. The mean corrected QT interval (QTc) of 3 electrocardiograms (ECGs) at rest was > 470 msec, and the Fridericia formula was used to correct the QT interval (QTcF); b. Resting ECG suggests the presence of a variety of clinically significant rhythmic, conduction, or ECG morphological abnormalities (e.g., complete left bundle branch block, third-degree atrioventricular block, second-degree atrioventricular block, and PR interval >). 250 msec); c. Presence of any factor that increases the risk of QTc prolongation or arrhythmic events, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death in an immediate family member under 40 years of age, or any concomitant medication that prolongs the QT interval; d. Functional assessment: left ventricular ejection fraction (LVEF) <50%, history of myocardial infarction, severe or unstable angina pectoris or coronary artery bypass surgery or cardiac insufficiency grade ≥ New York Heart Association (NYHA) grade 2 in the last 6 months; 6. Known history of prior interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid treatment; or acute onset or progressive pulmonary symptoms at baseline that are considered by the investigator to be inappropriate for enrollment or are judged to be high-risk factors for the possibility of interstitial lung disease and are not suitable for enrollment; 7. Diagnosed with immunodeficiency or active autoimmune disease (except a. controllable type I diabetes mellitus b. hypothyroidism [controlled with hormone replacement therapy alone] c. controllable celiac disease d. skin diseases that do not require systemic treatment [e.g., vitiligo, psoriasis, alopecia] e. any other disease that is not expected to recur if there is no external trigger)) 8. Grade 2 adverse reactions in the process of receiving PD-1/PD-L1 in the past, resulting in the occurrence of drug discontinuation. 9. Insufficient bone marrow reserve or organ function to meet the following laboratory limits: Absolute neutrophil count <1.5×10^9/L; b. Platelet count < 100×10^9/L; c. Hemoglobin < 90 g/L (<9 g/dL); d. Alanine aminotransferase > 2.5 times the upper limit of normal (ULN) Aspartate aminotransferase > 2.5×ULN f. Total bilirubin > 1.5×ULN; or presence of Gilbert's syndrome (unconjugated hyperbilirubinemia) creatinine > 1.5×ULN and creatinine clearance < 50 mL/min (calculated by Cockcroft-Gault formula); Creatinine clearance should only be confirmed if creatinine > 1.5× ULN; 9. Presence of active hepatitis B during the screening period (those who test positive for hepatitis B surface antigen (HBsAg) or HBcAb and are in the active stage of hepatitis B (HBV-DNA ≥ 104 cps/mL or ≥ 2000 IU/mL)); Hepatitis C (subjects with a positive hepatitis C antibody (Anti-HCV) test and a positive PCR test result for HCV RNA); People infected with human immunodeficiency virus (HIV); 10. Within 14 days before the first dose, there is uncontrolled diabetes mellitus or grade >1 hypokalemia, hyponatremia or abnormal corrected calcium laboratory test values despite standard drug treatment; 11. Females who are lactating or have a positive blood or urine pregnancy test result within 7 days before the first treatment of the study; 12. Judged by the investigator, there may be poor compliance with the procedures and requirements of the study (including but not limited to: the subject has serious or uncontrolled medical conditions, there are potential safety risks, interferes with the interpretation of the study results, affects the compliance of the trial, etc.); 13. Study participants are participating in another clinical study at the same time, unless it is an observational (non-interventional) clinical study or is in the follow-up period of an interventional study.

研究实施时间：

Study execute time：

从 From 2025-06-01 00:00:00至 To 2027-06-30 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2025-06-01 00:00:00 至 To 2027-06-01 00:00:00  

干预措施：

Interventions：

组别：

试验组

样本量：

24

Group：

Experimental group

Sample size：

干预措施：

首次放疗：采用晶格放疗，顶点剂量8-16Gy,外周剂量3Gy;后续常规姑息放疗>=40Gy;以PD-1/PD-L1 单克隆抗体为基础的治疗方案：PD-1/PD-L1单克隆抗体常规剂量联合其他研究者选择的治疗方案

干预措施代码：

Intervention：

First radiotherapy: lattice radiotherapy, apex dose 8-16 Gy, peripheral dose 3 Gy; Follow-up conventional palliative radiotherapy >=40 Gy; PD-1/PD-L1 monoclonal antibody-based regimen: PD-1/PD-L1 monoclonal antibody conventional dose in combination with other investigator's choice regimen

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 山东 

市(区县)：

  

Country：

China 

Province：

Shandong 

City：

 

单位(医院)：

山东第一医科大学附属省肿瘤医院 

单位级别：

三甲 

Institution
hospital：

Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

安全性评价

指标类型：

主要指标

Outcome：

Safety evaluation

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

晶格放疗顶点照射剂量限制性毒性

指标类型：

主要指标

Outcome：

Dose limited toxicity of Vertices for Lattice radiotherapy

Type：

Primary 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

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：

缓解持续时间

指标类型：

次要指标

Outcome：

Duration of 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：

客观缓解率

指标类型：

次要指标

Outcome：

Objective remission 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：

生物标志物

指标类型：

附加指标

Outcome：

Biomarker

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：

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：

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)：

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：

病例记录表

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

Case Record Form

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：

  2025-05-27 08:29:56