ChiCTR2000033591 版本V2.1 版本创建时间2021/01/25 16:29:33 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：

 ChiCTR2000033591 

最近更新日期：

Date of Last Refreshed on：

 2021-01-25 16:29:18 

注册时间：

Date of Registration：

 2020-06-06 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

信迪利单抗局部注射晚期实体瘤的疗效和安全性的探索性研究

Public title：

An exploratory study on the efficacy and safety of sintilimab in local injection of advanced solid tumor

注册题目简写：

English Acronym：

研究课题的正式科学名称：

信迪利单抗局部注射晚期实体瘤的疗效和安全性的探索性研究

Scientific title：

An exploratory study on the efficacy and safety of sintilimab in local injection of advanced solid tumor

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：

高峰 

研究负责人：

高峰 

Applicant：

Gao Feng 

Study leader：

Gao Feng 

申请注册联系人电话：

Applicant telephone：

 +86 13936552301

研究负责人电话：

Study leader's
telephone：

+86 13936552301

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：

 luoluoyanyan100@163.com

研究负责人电子邮件：

Study leader's E-mail：

 luoluoyanyan100@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：

黑龙江省哈尔滨市南岗区哈双路235号

研究负责人通讯地址：

黑龙江省哈尔滨市南岗区哈双路235号

Applicant address：

235 Hashuang Road, Nangang District, Harbin, Heilongjiang, China

Study leader's address：

235 Hashuang Road, Nangang District,Harbin, Heilongjiang, China

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：

黑龙江省农垦总局总医院

Applicant's institution：

Heilongjiang General Hospital of General Bureau of Agricultural Reclamation

研究负责人所在单位：

黑龙江省农垦总局总医院

Affiliation of the Leader：

Heilongjiang General Hospital of General Bureau of Agricultural Reclamation

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：

 NKZYY-2020-023

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：

黑龙江省农垦总局总医院伦理委员会

Name of the ethic committee：

Ethics Committee of the General Hospital of zhe General Administration of Land Reclamation of Heilongjiang

伦理委员会批准日期：

Date of approved by ethic committee：

 2020-06-22 00:00:00

伦理委员会联系人：

王利达

Contact Name of the ethic committee：

Wang Linda

伦理委员会联系地址：

黑龙江省哈尔滨市南岗区哈双路235号

Contact Address of the ethic committee：

235 Hashuang Road, Nangang District, Harbin, Heilongjiang, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 18686863660

伦理委员会联系人邮箱：

Contact email of the ethic committee：

 427334@qq.com

研究实施负责（组长）单位：

黑龙江省农垦总局总医院

Primary sponsor：

Heilongjiang General Hospital of General Bureau of Agricultural Reclamation

研究实施负责（组长）单位地址：

黑龙江省哈尔滨市南岗区哈双路235号

Primary sponsor's address：

235 Hashuang Road, Nangang District, Harbin, Heilongjiang, China

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

黑龙江

市(区县)：

哈尔滨

Country：

China

Province：

Heilongjiang

City：

Harbin

单位(医院)：

黑龙江省农垦总局总医院

具体地址：

南岗区哈双路235号

Institution
hospital：

Heilongjiang General Hospital of General Bureau of Agricultural Reclamation

Address：

235 Hashuang Road, Nangang District

经费或物资来源：

申办方

Source(s) of funding：

Sponsor

研究疾病：

实体瘤  

Target disease：

solid tumor

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：

主要目的：评估信迪利单抗局部注射治疗晚期实体瘤的疗效； 次要目的：评估信迪利单抗局部注射治疗晚期实体瘤的安全性。  

Objectives of Study：

main purpose: Evaluate the efficacy of local injection of sintilimumab in the treatment of advanced solid tumors. Secondary purpose: Evaluate the safety of local injection of sintilimumab in the treatment of advanced solid tumors.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

合格入选本研究的受试者必须符合以下所有标准：
1. 在实施任何试验相关流程之前，签署书面知情同意；
2. 年龄≥18周岁；
3. 组织学或细胞学证实的实体瘤；经研究者判断局部注药治疗可行。
4. 根据实体肿瘤疗效评价标准（RECIST 1.1版），至少有一处影像学可测量病灶。
5. 允许无症状或经局部治疗后症状稳定的脑转移受试者入组，只要受试者满足以下条件：
1) 中枢神经系统之外有可测量病灶
2) 无中枢神经系统症状或至少2周内症状无加重
6. ECOG评分0-2分；
7. 预期生存时间>3个月；
8. 足够器官功能，受试者需满足如下实验室指标：
1) 近14天未输血的情况下，血小板≥80×10^9/L；
2) 总胆红素≤1.5倍正常值上限（ULN）
3) 天门冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）在≤2.5倍ULN（有肝转移的受试者允许ALT 或AST ≤5×ULN）；
4) 血肌酐≤1.5倍ULN并且肌酐清除率（采用Cockcroft-Gault 公式计算）≥60 ml/min；
5) 凝血功能良好，定义为国际标准化比值（INR）或凝血酶原时间（PT）≤1.5倍ULN；
6) 甲状腺功能正常，定义为促甲状腺激素（TSH）在正常范围内。如基线TSH超出正常范围，如果总T3（或FT3）及FT4在正常范围内的受试者亦可入组；
7) 心肌酶谱在正常范围内（如研究者综合判断为不具有临床意义的单纯实验室异常也允许入组）；
9. 对于育龄期女性受试者，应在接受首次研究药物给药（第1周期第1天）之前的3天内接受尿液或血清妊娠试验且结果为阴性。如果尿液妊娠试验结果无法确认为阴性，则要求进行血液妊娠试验。非育龄期女性定义为绝经后至少１年，或进行过手术绝育或子宫切除术；
10. 如存在受孕风险，所有受试者（不论男性或女性）均需在整个治疗期间直至治疗末次研究药物给药后120天（或末次研究药物给药后180天）内采用年失败率低于1%的避孕措施。

Inclusion criteria

Eligible subjects for this study must meet all of the following criteria:
1. Patients who sign the written informed consent before implementing any test related process;
2. Patients aged >= 18 years;
3. Patients with solid tumors confirmed by histology or cytology; the local injection therapy is feasible according to the judgment of researchers.
4. According to the evaluation standard of solid tumor efficacy (RECIST version 1.1), there is at least one imaging measurable focus.
5. Subjects with asymptomatic or stable symptoms after local treatment are allowed to enter the group as long as they meet the following conditions:
(1) Measurable lesions outside the central nervous system
(2) No central nervous system symptoms or no aggravation within at least 2 weeks
6. ECoG score 0-2;
7. Expected survival time > 3 months;
8. Sufficient organ function, subjects need to meet the following laboratory indicators:
(1) Without blood transfusion in the past 14 days, platelet >= 80 * 10^9 / L;
(2) Total bilirubin <= 1.5 times upper limit of normal value (ULN)
(3) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were <= 2.5 times ULN (ALT or AST <= 5 * ULN were allowed for subjects with liver metastasis);
(4) Blood creatinine <= 1.5 times ULN and creatinine clearance (calculated by Cockcroft Gault formula) >= 60 ml / min;
(5) The coagulation function was good, defined as INR or PT <= 1.5 times ULN;
(6) Normal thyroid function, defined as TSH in the normal range. If the baseline TSH is out of the normal range, subjects with total T3 (or FT3) and FT4 in the normal range can also be enrolled;
(7) The myocardial zymogram was in the normal range (for example, the single laboratory abnormality without clinical significance judged by the researchers was also allowed to enter the group);
9. For female subjects of childbearing age, the urine or serum pregnancy test shall be conducted within 3 days before the first study drug administration (the first day of the first cycle) and the result shall be negative. If the result of urine pregnancy test cannot be confirmed as negative, blood pregnancy test is required. Women of non childbearing age are defined as postmenopausal women at least 1 year, who have undergone surgical sterilization or hysterectomy;
10. If there is a risk of conception, all subjects (male or female) should adopt contraceptive measures with an annual failure rate of less than 1% during the whole treatment period and up to 120 days (or 180 days) after the last study drug administration.

排除标准：

符合以下标准的受试者不能入选本研究：
1. 首次给药前2年内发生过需要全身性治疗（例如使用缓解疾病药物、糖皮质激素或免疫抑制剂）的活动性自身性免疫疾病。替代疗法（例如甲状腺素、胰岛素或者用于肾上腺或垂体机能不全的生理性糖皮质激素等）不视为全身性治疗；
2. 既往接受过下列疗法：抗PD-1、抗PD-L1或抗PD-L2药物或者针对另一种刺激或协同抑制T细胞受体（例如，CTLA-4、OX-40、CD137）的药物；
3. 研究首次给药前7天内正在接受全身性糖皮质激素治疗（不包括喷鼻、吸入性或其他途径的局部糖皮质激素）或任何其他形式的免疫抑制疗法；注：允许使用生理剂量的糖皮质激素（≤10 mg/天的泼尼松或等效药物）；
4. 当前正在参与干预性临床研究治疗，或在首次给药前4周内接受过其他研究药物或使用过研究器械治疗；
5. 已知异体器官移植（角膜移植除外）或异体造血干细胞移植；
6. 已知对本研究药物信迪利单抗活性成分或辅料过敏者;
7. 在开始治疗前，尚未从任何干预措施引起的毒性和/或并发症中充分恢复（即，≤1级或达到基线，不包括乏力或脱发）；
8. 已知人类免疫缺陷病毒（HIV）感染史（即HIV 1/2抗体阳性）；
9. 未经治疗的活动性乙肝（定义为HBsAg阳性同时检测到HBV-DNA拷贝数大于所在研究中心检验科正常值上限）；注：符合下列标准的乙肝受试者亦可入组：
1) 首次给药前HBV病毒载量<1000拷贝/ml（200 IU/ml），受试者应在整个研究化疗药物治疗期间接受抗HBV治疗避免病毒再激活
2) 对于抗HBc（+）、HBsAg（-）、抗HBs（-）和HBV病毒载量（-）的受试者，不需要接受预防性抗HBV治疗，但是需要密切监测病毒再激活
10. 活动性的HCV感染受试者（HCV抗体阳性且HCV-RNA水平高于检测下限）；
11. 首次给药之前（第1周期，第1天）30天内接种过活疫苗；注：允许首次给药前30天内接受针对季节性流感的注射用灭活病毒疫苗；但是不允许接受鼻内用药的减毒活流感疫苗。
12. 妊娠或哺乳期妇女；
13. 已知活动性的酒精或药物滥用或依赖性的患者
14. 存在任何严重或不能控制的全身性疾病，例如：
1) 静息心电图在节律、传导或形态上出现有重大且症状严重难以控制的异常，如完全性左束支传导阻滞，Ⅱ度以上心脏传导阻滞，室性心律失常或心房颤动；
2) 不稳定型心绞痛，充血性心力衰竭，纽约心脏病协会（NYHA）分级≥ 2 级的慢性心衰；
3) 入组前6个月内出现心肌梗死；
4) 血压控制不理想（收缩压＞140 mmHg，舒张压＞90 mmHg）；
5) 首次给药前1年内存在需要糖皮质激素治疗的非感染性肺炎病史，或当前存在临床活动性间质性肺病；
6) 活动性肺结核；
7) 存在需要全身性治疗的活动性或未能控制的感染；
8) 存在临床活动性憩室炎、腹腔脓肿、胃肠道梗阻；
9) 肝脏疾病如肝硬化、失代偿性肝病、急性或慢性活动性肝炎；
10) 糖尿病控制不佳（空腹血糖（FBG）＞10mmol/L）；
11) 尿常规提示尿蛋白≥++，且证实24小时尿蛋白定量＞1.0 g者；
12) 存在精神障碍且无法配合治疗的受试者；
15. 有可能干扰试验结果、妨碍受试者全程参与研究的病史或疾病证据、治疗或实验室检查值异常，或研究者认为其他不适合入组的情况研究者认为存在其他潜在风险不适合参加本研究。

Exclusion criteria：

Subjects who met the following criteria were excluded from the study:
1. Active autoimmune diseases of patients requiring systemic treatment (such as the use of disease alleviation drugs, glucocorticoids or immunosuppressants) occurred within 2 years before the first administration. Substitution therapy (such as thyroxine, insulin or physiological glucocorticoid for adrenal or pituitary insufficiency) is not considered as systemic therapy;
2. Previously received the following therapies: anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs or drugs for another stimulation or synergistic inhibition of T cell receptor (for example, CTLA-4, OX-40, CD137);
3. Study the patients who are receiving systemic glucocorticoid treatment (excluding local glucocorticoids in nasal spray, inhalation or other ways) or any other form of immunosuppressive therapy within 7 days before the first administration; note: allow to use physiological dose of glucocorticoids (< 10 mg / day of prednisone or equivalent);
4. Patients who are currently participating in the intervention clinical research treatment, or who have received other research drugs or used research instruments within 4 weeks before the first administration;
5. Patients with known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation;
6. Patients who are known to be allergic to the active ingredients or excipients of the investigational drug cindilimab;
7. Patients who have not fully recovered from toxicity and / or complications caused by any intervention before the start of treatment (i.e., <= level 1 or baseline, excluding fatigue or alopecia);
8. Patients with known HIV infection history (i.e. HIV 1 / 2 antibody positive);
9. Untreated active hepatitis B patients (defined as HBsAg positive and HBV-DNA copy number greater than the upper limit of the normal value of the laboratory in the research center); note: hepatitis B patients meeting the following criteria can also be included in the group:
(1) Before the first administration, the HBV viral load was less than 1000 copies / ml (200 IU / ml). The subjects should receive anti HBV treatment to avoid virus reactivation during the whole chemotherapy treatment period of the study
(2) For subjects with anti HBC +, HBsAg (-), anti HBS (-), and HBV viral load (-), prophylactic anti HBV treatment is not required, but virus reactivation needs to be closely monitored
10. Active HCV infected subjects (HCV antibody positive and HCV-RNA level higher than the detection limit);
11. Patients who have been vaccinated with live vaccine within 30 days before the first administration (cycle 1, day 1); note: it is allowed to receive inactivated virus vaccine for injection against seasonal influenza within 30 days before the first administration; but it is not allowed to receive live attenuated influenza vaccine for intranasal administration.
12. Pregnant or lactating women;
13. Patients with known active alcohol or drug abuse or dependence;
14. Patients with any serious or uncontrollable systemic disease, such as:
(1) The resting ECG showed significant abnormalities in rhythm, conduction or morphology, such as complete left bundle branch block, heart conduction block above degree Ⅱ, ventricular arrhythmia or atrial fibrillation;
(2) Unstable angina, congestive heart failure, chronic heart failure with NYHA grade >= 2;
(3) Myocardial infarction occurred within 6 months before admission;
(4) Blood pressure control was not ideal (systolic pressure > 140 mmHg, diastolic pressure > 90 mmHg);
(5) There was a history of noninfectious pneumonia requiring glucocorticoid treatment within one year before the first administration, or there was currently clinical active interstitial lung disease;
(6) Active tuberculosis;
(7) There are active or uncontrollable infections requiring systemic treatment;
(8) There were clinical active diverticulitis, abdominal abscess and gastrointestinal obstruction;
(9) Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis;
(10) Poor diabetes control (FBG > 10mmol / L);
(11) Routine urine test showed that urine protein was >= + +, and 24-hour urine protein was more than 1.0g;
(12) Subjects with mental disorders who could not cooperate with the treatment;
15. Patients with history or disease evidence that may interfere with the test results, prevent the subjects from participating in the whole study, patients with abnormal treatment or laboratory test values, or other situations that the researchers think are not suitable for inclusion, the researchers think that there are other potential risks that are not suitable for the study.

研究实施时间：

Study execute time：

从 From 2020-06-01 00:00:00至 To 2021-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2020-06-01 00:00:00 至 To 2022-05-31 00:00:00

干预措施：

Interventions：

组别：

试验组

样本量：

 30

Group：

experimental group

Sample size：

干预措施：

信迪利单抗局部注射

干预措施代码：

Intervention：

sintilimab local injection

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 黑龙江 

市(区县)：

 哈尔滨 

Country：

China

Province：

Heilongjiang

City：

Harbin

单位(医院)：

 黑龙江省农垦总局总医院 

单位级别：

 三级甲等 

Institution
hospital：

Heilongjiang General Hospital of General Bureau of Agricultural Reclamation

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

根据RECIST V1.1评估受试者的客观缓解率（ORR；局部注射病灶作为靶病灶评估）

指标类型：

主要指标

Outcome：

assessment of the objective response rate (ORR; local injection of the lesion as a target lesion) in the subjects according to RECIST v1.1

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

根据RECIST V1.1评估受试者的疾病进展时间（TTP；局部注射病灶作为靶病灶）；

指标类型：

次要指标

Outcome：

time to disease progression (TTP) was assessed according to RECIST v1.1

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

根据RECIST V1.1评估受试者的疾病控制率（DCR；局部注射病灶作为靶病灶）

指标类型：

次要指标

Outcome：

assessment of disease control rate (DCR; local injection as target) in subjects according to RECIST v1.1

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

评估信迪利单抗联合含铂双药化疗的安全性和耐受性：包括不良事件（AE）和严重不良事件（SAE）的发生率，AE/SAE导致治疗终止的发生率

指标类型：

次要指标

Outcome：

evaluation of the safety and tolerability of cindilimab combined with platinum containing dual drug chemotherapy: including the incidence of adverse events (AE) and serious adverse events (SAE), and the incidence of termination of treatment caused by AE / SAE

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

其他病灶远隔效应

指标类型：

附加指标

Outcome：

distant effect of other lesions

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：

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：

征募研究对象情况：

Recruiting status：

正在进行

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）：

本研究为单臂研究，不进行随机。

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

This study is a one-arm study and is not randomized.

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：

N/A

Blinding：

N/A

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

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）：

试验完成后6个月共享数据，网络平台共享，ResMan (www.medresman.org.cn)

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

6 months after the trial is completed, data sharing, network platform sharing, ResMan (www.medresman.org.cn)

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：

数据的采集使用CRF

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

Data collection using CRF

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2020-06-06 14:13:35