ChiCTR2100049390 版本V2.0 版本创建时间2022/03/15 17:34:32 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：

ChiCTR2100049390 

最近更新日期：

Date of Last Refreshed on：

2022-03-15 17:24:11 

注册时间：

Date of Registration：

2021-08-01 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

信迪利单抗联合安罗替尼和白蛋白紫杉醇治疗二线及以上广泛期小细胞肺癌的前瞻性、单臂、单中心、II期探索性研究

Public title：

A prospective, single-arm, single-center, phase II exploratory study of Sintilimab combined with anlotinib and albumin paclitaxel in the treatment of second-line and above extensive-stage small cell lung cancer

注册题目简写：

English Acronym：

研究课题的正式科学名称：

信迪利单抗联合安罗替尼和白蛋白紫杉醇治疗二线及以上广泛期小细胞肺癌的前瞻性、单臂、单中心、II期探索性研究

Scientific title：

A prospective, single-arm, single-center, phase II exploratory study of Sintilimab combined with anlotinib and albumin paclitaxel in the treatment of second-line and above extensive-stage small cell lung 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：

韩晓 

研究负责人：

王哲海 

Applicant：

Han Xiao 

Study leader：

Wang Zhehai 

申请注册联系人电话：

Applicant telephone：

+86 13583183578

研究负责人电话：

Study leader's telephone：

+86 13505414672

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：

hxzbb1983@163.com

研究负责人电子邮件：

Study leader's E-mail：

wzhai8778@sina.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公路440号

研究负责人通讯地址：

山东省济南市槐荫区济兖公路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：

山东省肿瘤防治研究院

Applicant's institution：

Shandong Cancer Research Institute

研究负责人所在单位：

山东省肿瘤防治研究院

Affiliation of the Leader：

Shandong Cancer Research Institute

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：

SDZLEC2021-055-02

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肿瘤医院伦理委员会

Name of the ethic committee：

Ethics Committee of Shandong First Medical University Affiliated Tumor Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

2021-06-15 00:00:00

伦理委员会联系人：

李朝伟

Contact Name of the ethic committee：

Li Chaowei

伦理委员会联系地址：

山东省济南市槐荫区济兖公路440号

Contact Address of the ethic committee：

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

伦理委员会联系人电话：

Contact phone of the ethic committee：

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：

山东省肿瘤医院

Primary sponsor：

Shandong Cancer Hospital

研究实施负责（组长）单位地址：

山东省济南市槐荫区济兖公路440号

Primary sponsor's address：

440 Jiyan Road, Huaiyin District, Ji'nan, 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

市(区县)：

济南

Country：

China

Province：

Shandong

City：

Ji'nan

单位(医院)：

山东省肿瘤医院

具体地址：

槐荫区济兖公路440号

Institution
hospital：

Shandong Cancer Hospital

Address：

440 Jiyan Road, Huaiyin District

经费或物资来源：

免费研究药物

Source(s) of funding：

Free research drugs

Target disease：

small cell lung cancer, SCLC

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：

评估信迪利单抗联合安罗替尼和白蛋白紫杉醇治疗二线及以上广泛期小细胞肺癌的有效性和安全性。  

Objectives of Study：

To evaluate the effectiveness and safety of sintilimab combined with anlotinib and albumin paclitaxel in the treatment of second-line and above extensive-stage small cell lung 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.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周岁且<=75周岁；
3.组织学或细胞学证实的广泛期小细胞肺癌（SCLC）；
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。位于既往放疗照射野内的病灶如证实发生进展可视为可测量病灶；
5.既往至少接受过一线及以上针对SCLC的系统性治疗；
6.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；
(3)无需糖皮质激素治疗，或入组前7天内停用糖皮质激素治疗，或入组前7天内糖皮质激素用量稳定且减至10mg/天泼尼松（或等效剂量）以下；
7.允许受试者接受姑息性放射治疗（包括针对症状性脑转移的颅脑放疗），但放疗需在首次研究药物给药前至少1周结束，并且放疗相关的毒性恢复至小于或等于1度（CTCAE 5.0，脱发除外）；
8.ECOG评分0-1分；
9.预期生存时间>3个月；
10.足够器官功能，受试者需满足如下实验室指标：
(1)近14天未使用粒细胞集落刺激因子的情况下，中性粒细胞绝对值（ANC）>=1.5x10^9/L；
(2)近14天未输血的情况下，血小板>=100x10^9/L；
(3)近14天内无输血或使用促红细胞生成素的情况下，血红蛋白>9g/dL；
(4)总胆红素<=1.5倍正常值上限（ULN）；
(5)天门冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）在<=2.5xULN（有肝转移的受试者允许ALT 或AST<=5xULN）；
(6)血肌酐<=1.5xULN并且肌酐清除率（采用Cockcroft-Gault 公式计算）>=60 ml/min；
(7)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）<=1.5xULN；
(8)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；
(9)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）；
11.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；
12.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

1.Sign written informed consent before implementing any trial-related procedures;
2.Aged 18 to 75 years;
3.Extensive-stage small cell lung cancer (SCLC) confirmed by histology or cytology;
4.According to the evaluation criteria for the efficacy of solid tumors (RECIST version 1.1), there is at least one imaging measurable lesion. The lesions located in the radiation field of the previous radiotherapy can be regarded as measurable lesions if the progress is confirmed;
5.Have received at least first-line or above systemic treatment for SCLC in the past;
6.Subjects with brain metastases asymptomatic or with stable symptoms after local treatment are allowed to be included in the group, as long as the subjects meet the following conditions:
(1)There are measurable lesions outside the central nervous system;
(2)No symptoms of central nervous system or no worsening of symptoms within at least 2 weeks;
(3)No need for glucocorticoid treatment, or stop glucocorticoid treatment within 7 days before enrollment, or the dosage of glucocorticoid is stable and reduced to less than 10mg/day prednisone (or equivalent dose) within 7 days before enrollment;
7.Subjects are allowed to receive palliative radiotherapy (including craniocerebral radiotherapy for symptomatic brain metastases), but the radiotherapy needs to be completed at least 1 week before the first study drug administration, and the radiotherapy-related toxicity is restored to less than or equal to 1 Degree (CTCAE 5.0, except for hair loss);
8.ECOG score 0-1 points;
9.Expected survival time> 3 months;
10.Sufficient organ function, subjects need to meet the following laboratory indicators:
(1)The absolute value of neutrophils (ANC) >= 1.5x10^9/L when no granulocyte colony stimulating factor is used in the past 14 days;
(2)In the case of no blood transfusion in the past 14 days, platelets >=100x10^9/L;
(3)In the past 14 days without blood transfusion or erythropoietin, hemoglobin>9g/dL;
(4)Total bilirubin <=1.5 times the upper limit of normal (ULN);
(5)Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) within <=2.5xULN (subjects with liver metastases are allowed to have ALT or AST <=5xULN);
(6)Serum creatinine <=1.5xULN and creatinine clearance rate (calculated by Cockcroft-Gault formula) >=60 ml/min;
(7)Good coagulation function, defined as International Normalized Ratio (INR) or Prothrombin Time (PT) <= 1.5xULN;
(8)Normal thyroid function is defined as thyroid stimulating hormone (TSH) within the normal range. If the baseline TSH is outside the normal range, subjects whose total T3 (or FT3) and FT4 are within the normal range can also be included in the group;
(9)Myocardial enzyme spectrum is within the normal range (for example, simple laboratory abnormalities that are judged by the investigator to be of no clinical significance are also allowed to be included in the group);
11.For female subjects of childbearing age, a urine or serum pregnancy test and the result should be negative within 3 days before receiving the first study drug administration (day 1 of cycle 1). If the urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is required. Women of non-bearing age are defined as at least 1 year after menopause, or have undergone surgical sterilization or hysterectomy;
12.If there is a risk of conception, all subjects (whether male or female) need to adopt a low annual failure rate during the entire treatment period until 120 days after the last study drug administration (or 180 days after the last study drug administration) Less than 1% of contraceptive measures.

排除标准：

1.既往接受过任何针对SCLC的抗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）的药物等；
2.首次给药前5年内诊断为SCLC之外的其他恶性疾病（不包括经过根治的皮肤基底细胞癌、皮肤鳞状上皮癌、和/或经过根治性切除的原位癌）；
3.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；
4.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；
5.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）；
6.存在临床上不可控制的胸腔积液/腹腔积液（不需要引流积液或停止引流3天积液无明显增加的受试者可以入组）；
7.已知异体器官移植（角膜移植除外）或异体造血干细胞移植；
8.已知对本研究药物信迪利单抗、安罗替尼、白蛋白紫杉醇等活性成分或辅料过敏者;
9.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）；
10.已知人类免疫缺陷病毒（HIV）感染史（即HIV 1/2抗体阳性）；
11.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；
12.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）；
13.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。
14.妊娠或哺乳期妇女；
15.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；
16.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：

1.Have previously received any anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs for SCLC or for another stimulus or synergistic inhibition of T cell receptors (for example, CTLA-4, OX-40, CD137) Drugs, etc.;
2.Diagnosis of other malignant diseases other than SCLC within 5 years before the first administration (excluding radically cured skin basal cell carcinoma, skin squamous cell carcinoma, and/or radically excised carcinoma in situ);
3.Are currently participating in interventional clinical research treatment, or have received other research drugs or used research devices within 4 weeks before the first administration;
4.An active autoimmune disease that requires systemic treatment (such as the use of disease-relieving drugs, glucocorticoids, or immunosuppressive agents) occurred within 2 years before the first administration. Alternative therapies (such as thyroxine, insulin, or physiological glucocorticoids for adrenal or pituitary insufficiency, etc.) are not considered systemic treatments;
5.Are receiving systemic glucocorticoid therapy (excluding nasal spray, inhaled or other local glucocorticoids) or any other form of immunosuppressive therapy within 7 days before the first administration of the study;
Note: The use of physiological doses of glucocorticoids (<=10 mg/day prednisone or equivalent drugs) is allowed;
6.There is clinically uncontrollable pleural effusion/abdominal effusion (subjects who do not need to drain the effusion or stop drainage for 3 days without a significant increase in effusion can be included in the group);
7.Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation;
8.Patients are known to be allergic to active ingredients or excipients such as Sintilimab, Anlotinib, Albumin Paclitaxel, etc.;
9.Before starting treatment, have not fully recovered from toxicity and/or complications caused by any intervention (i.e., <= Grade 1 or reached baseline, excluding fatigue or hair loss);
10.Known history of human immunodeficiency virus (HIV) infection (ie HIV 1/2 antibody positive);
11.Untreated active hepatitis B (defined as HBsAg positive and the number of HBV-DNA copies detected at the same time is greater than the upper limit of the normal value of the laboratory department of the research center);
Note: Hepatitis B subjects who meet the following criteria can also be included in the group:
(1)Before the first administration, the HBV viral load is less than 1000 copies/ml (200 IU/ml), and the subject should receive anti-HBV treatment during the entire study chemotherapy drug treatment to avoid viral reactivation;
(2)For subjects with anti-HBc (+), HBsAg (-), anti-HBs (-) and HBV viral load (-), there is no need to receive preventive anti-HBV treatment, but close monitoring of virus reactivation is required;
12.Active HCV infected subjects (HCV antibody-positive and HCV-RNA level is higher than the lower limit of detection);
13.Live vaccines have been vaccinated within 30 days before the first administration (cycle 1, day 1);
Note: It is allowed to receive inactivated virus vaccine for seasonal influenza injection within 30 days before the first administration; However, it is not allowed to receive live attenuated influenza vaccine for intranasal administration.
14.Pregnant or lactating women;
15.There are any serious or uncontrollable systemic diseases, such as:
(1)The resting electrocardiogram has major abnormalities in rhythm, conduction or morphology that are severe and difficult to control, such as complete left bundle branch block, heart block above degree II, ventricular arrhythmia or atrial fibrillation;
(2)Unstable angina pectoris, congestive heart failure, chronic heart failure of New York Heart Association (NYHA) grade >= 2;
(3)Myocardial infarction occurred within 6 months before enrollment;
(4)Unsatisfactory blood pressure control (systolic blood pressure>140 mmHg, diastolic blood pressure>90 mmHg);
(5)A history of non-infectious pneumonia requiring glucocorticoid treatment within 1 year before the first administration, or current clinically active interstitial lung disease;
(6)Active tuberculosis;
(7)There is an active or uncontrolled infection that requires systemic treatment;
(8)There is clinically active diverticulitis, abdominal abscess, gastrointestinal obstruction;
(9)Liver diseases such as liver cirrhosis, decompensated liver disease, acute or chronic active hepatitis;
(10)Poor control of diabetes (fasting blood glucose (FBG)> 10mmol/L);
(11)Urine routines suggest that urine protein is >=++, and the 24-hour urine protein quantification is confirmed to be greater than 1.0 g;
(12)Subjects who have mental disorders and cannot cooperate with treatment;
16.Any medical history or disease evidence that may interfere with the study results, prevent the subjects from participating fully in the study, abnormal values of treatment or laboratory tests, or other conditions that the investigator considers inappropriate for the study because of other potential risks that the investigator considers inappropriate for the study.

研究实施时间：

Study execute time：

从 From 2021-06-15 00:00:00至 To 2023-06-14 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2021-08-01 00:00:00 至 To 2022-06-14 00:00:00  

干预措施：

Interventions：

组别：

试验组

样本量：

30

Group：

Test group

Sample size：

干预措施：

信迪利单抗+安罗替尼+白蛋白紫杉醇

干预措施代码：

Intervention：

Sintilimab + Anlotinib + Albumin Paclitaxel

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)：

山东省肿瘤医院 

单位级别：

三级甲等 

Institution
hospital：

Shandong Cancer Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

客观缓解率

指标类型：

主要指标

Outcome：

objective remission rate, ORR

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, 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：

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：

缓解持续时间

指标类型：

次要指标

Outcome：

Duration of remission, DOR

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：

安全性

指标类型：

次要指标

Outcome：

safety

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

 其它  

说明

Fate of sample：

0thers  

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）：

不适用。

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

Not applicable.

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：

Blinding：

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）：

不共享

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

Not shared

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：

病例报告表

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

CRF

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2021-08-01 23:46:04