ChiCTR2300079125 版本V1.0 版本创建时间2023/12/26 10:36:00 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：

ChiCTR2300079125 

最近更新日期：

Date of Last Refreshed on：

2023-12-26 10:35:56 

注册时间：

Date of Registration：

2023-12-26 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

卡铂+依托泊苷联合阿得贝利单抗及胸部姑息放疗一线治疗广泛期小细胞肺癌的单臂、前瞻性Ⅱ期临床研究

Public title：

Single-arm, prospective Phase II clinical study of carboplatin plus etoposide combined with adebrelimab and thoracic palliative radiotherapy in the first-line treatment of extensive small cell lung

注册题目简写：

English Acronym：

研究课题的正式科学名称：

卡铂+依托泊苷联合阿得贝利单抗及胸部姑息放疗一线治疗广泛期小细胞肺癌的单臂、前瞻性Ⅱ期临床研究

Scientific title：

Single-arm, prospective Phase II clinical study of carboplatin plus etoposide combined with adebrelimab and thoracic palliative radiotherapy in the first-line treatment of extensive small cell lung

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：

徐礼 

研究负责人：

徐礼 

Applicant：

Li Xu 

Study leader：

Li Xu 

申请注册联系人电话：

Applicant telephone：

+86 731 8976 2815

研究负责人电话：

Study leader's telephone：

+86 731 8976 2815

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：

xuli@hnca.org.cn

研究负责人电子邮件：

Study leader's E-mail：

xuli@hnca.org.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：

中国湖南省长沙市岳麓区桐梓坡路283号

研究负责人通讯地址：

中国湖南省长沙市岳麓区桐梓坡路283号

Applicant address：

283 Tongzipo Road, Yuelu District, Changsha City, Hunan Province, China

Study leader's address：

283 Tongzipo Road, Yuelu District, Changsha City, Hunan Province, 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：

湖南省肿瘤医院

Applicant's institution：

Hunan Cancer Hospital

研究负责人所在单位：

湖南省肿瘤医院

Affiliation of the Leader：

Hunan Cancer Hospital

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：

2023年科研快审[66]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：

湖南省肿瘤医院伦理委员会

Name of the ethic committee：

Ethics Committee of Hunan Cancer Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

2023-06-15 00:00:00

伦理委员会联系人：

王冉冉

Contact Name of the ethic committee：

Ranran Wang

伦理委员会联系地址：

中国湖南省长沙市岳麓区桐梓坡路283号

Contact Address of the ethic committee：

283 Tongzipo Road, Yuelu District, Changsha City, Hunan Province, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 731 8976 2695

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：

湖南省肿瘤医院

Primary sponsor：

Hunan Cancer Hospital

研究实施负责（组长）单位地址：

中国湖南省长沙市岳麓区桐梓坡路283号

Primary sponsor's address：

283 Tongzipo Road, Yuelu District, Changsha City, Hunan Province, 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)：

湖南

市(区县)：

长沙

Country：

China

Province：

Hunan

City：

Changsha

单位(医院)：

湖南省肿瘤医院

具体地址：

中国湖南省长沙市岳麓区桐梓坡路283号

Institution
hospital：

Hunan Cancer Hospital

Address：

283 Tongzipo Road, Yuelu District, Changsha City, Hunan Province, China

经费或物资来源：

湖南省肿瘤医院科研攀登计划

Source(s) of funding：

Hunan Cancer Hospital scientific research climbing plan

Target disease：

Initial treatment of patients with extensive small cell lung cancer

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：

1、计划前瞻性入组近50例卡铂+依托泊苷联合阿得贝利单抗及胸部姑息放疗一线治疗广泛期小细胞肺癌的患者，初步探索该治疗模式的治疗效果、毒副反应等的相关性。 2、深入研究该治疗模式中，小细胞肺癌的不同分型SCLC-A/N/Y/P型、PD-L1的不同表达水平的疗效差异等，并探索具有临床意义的疗效预测标志物。  

Objectives of Study：

1. It is planned to prospectively enroll nearly 50 patients with carboplatin + etoposide combined with adebrelimab and thoracic palliative radiotherapy for first-line treatment of extensive small-cell lung cancer, and preliminarily explore the correlation of therapeutic effect and toxic side effects of this treatment mode. 2. In this treatment mode, the therapeutic effects of different types of small cell lung cancer SCLC-A/N/Y/P and different expression levels of PD-L1 were studied in depth, and the therapeutic effect prediction markers with clinical significance were explored.

药物成份或治疗方案详述：

阿得贝利单抗：20 mg/kg，在联合治疗或维持治疗期间，在每个为期3周的周期中于第1天，以静脉输注的形式给药，联合治疗期间首先输注。 化疗方案：依托泊苷：100 mg/m2，在联合治疗期间，在每个为期3周的周期中于第1-3天，以静脉输注的形式给药，最多4个周期； 卡铂：AUC为5，在联合治疗期间，在每个为期3周的周期中于第1天，以静脉输注的形式给药，最多4个周期； 胸部放疗：30Gy/10f/14d，3 Gy/次，每日一次；放疗靶区：根据化疗后CT勾画原发灶靶区，参考化疗前CT勾画淋巴结区域；仅针阿得贝利单抗联合化疗后疗效评价为PR或缩小SD的患者的患者。放疗期间及放疗后，保持阿得贝利单抗的单药维持治疗。 

Description for medicine or protocol of treatment in detail：

Adebrelimab: 20 mg/kg, administered as an intravenous infusion on day 1 of each 3-week cycle during combination therapy or maintenance therapy, with the infusion first during combination therapy. Chemotherapy regimen: etoposide: 100 mg/m2, administered as an intravenous infusion on day 1-3 of each 3-week cycle for up to 4 cycles during the combination therapy; Carboplatin: with an AUC of 5, administered as an intravenous infusion on day 1 of each 3-week cycle for a maximum of 4 cycles during combination therapy; Chest radiotherapy: 30Gy/10f/14d, 3 Gy/ times, once a day; Radiotherapy target area: Primary target area was delineated by CT after chemotherapy, and lymph node area was delineated by CT before chemotherapy. Only patients with adbelizumab combined with chemotherapy were evaluated for efficacy after PR or reduced SD. Monotherapy with adbelimab was maintained during and after radiotherapy. 

纳入标准：

1.年龄≥18周岁； 2.美国东部肿瘤协作组（ECOG）体能状态为0或1； 3.经组织学或细胞学证实的广泛期ES-SCLC患者； 4.至少存在一个根据RECIST v1.1标准评估的可测量病灶； 5.预期寿命超过3个月； 6.既往未接受过系统性抗肿瘤治疗； 7.足够的器官功能： 1)骨髓功能：中性粒细胞绝对计数≥1.5×10^9 /L，血小板计数≥90 ×10^9 /L，血红蛋白≥90g/L； 2)肝功能：定义为总胆红素水平≤1.5 倍正常上限（ULN）；不存在肝转移的患者，谷草转氨酶（AST）和谷丙转氨酶（ALT）水平≤3倍ULN；对于有记录到的肝脏转移的患者，AST 和 ALT 水平≤5 倍ULN； 3)肾功能：定义为血清肌酐≤1.5倍ULN；尿常规检查尿蛋白少于 2+，如患者在基线水平的尿蛋白≥2+时应收集24小时尿液并证明24小时尿蛋白定量检测≤1g； 4)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；若受试者正接受抗凝治疗，只要 PT 在抗凝药物拟定的使用范围内即可； 8.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 7 天内呈尿液或血清妊娠试验阴性。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；对于男性，须同意在试验期间和末次给予试验药物后8周内采用适当的方法避孕或已手术绝育； 9.能够依从研究和随访程序； 10.在任何试验相关流程实施之前，签署书面知情同意。

Inclusion criteria

1. Age ≥18 years old; 2. The physical status of the American Eastern Cancer Consortium (ECOG) was 0 or 1; 3. Patients with extensive stage ES-SCLC confirmed by histology or cytology; 4. The presence of at least one measurable lesion assessed according to the RECIST v1.1 criteria; 5. Life expectancy is more than 3 months; 6. Have not received systemic anti-tumor therapy before; 7. Adequate organ function: 1) Bone marrow function: absolute neutrophil count ≥1.5×10^9 /L, platelet count ≥90 ×10^9 /L, hemoglobin ≥90g/L; 2) Liver function: defined as total bilirubin level ≤1.5 times the upper limit of normal (ULN); In patients without liver metastasis, the levels of glutamic oxalic aminotransferase (AST) and glutamic pyruvic aminotransferase (ALT) were less than 3 times ULN; For patients with recorded liver metastasis, AST and ALT levels were ≤5 ULN; 3) Renal function: defined as serum creatinine ≤1.5 times ULN; Urine protein is less than 2+ for routine urine examination. If the patient has urine protein ≥2+ at baseline level, 24-hour urine should be collected and 24-hour urine protein quantitative detection ≤1g should be demonstrated. 4) Good coagulation function, defined as International standardized ratio (INR) or prothrombin time (PT) ≤1.5 times ULN; If the subject is receiving anticoagulant therapy, as long as PT is within the intended range of anticoagulant drug use; 8. For female subjects of reproductive age, urine or serum pregnancy tests should be negative within 7 days prior to receiving the first study drug administration (cycle 1, day 1). If the urine pregnancy test results cannot be confirmed as negative, a blood pregnancy test is required; For men, consent to use appropriate methods of contraception or surgical sterilization during the trial period and within 8 weeks after the last dose of the trial drug; 9. Able to comply with research and follow-up procedures; 10.Sign written informed consent before any trial related procedures are implemented.

排除标准：

1.对试验药物过敏； 2.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； 3.既往接受过任何T细胞共刺激或免疫检查点治疗，包括但不限于细胞毒性T 淋巴细胞相关抗原-4 （ cytotoxic Tlymphocyte-associated antigen-4，CTLA-4）抑制剂、PD-1抑制剂、PD-L1/2抑制剂或其他靶向T细胞的药物； 4.有症状的脑转移； 5.未接受治疗的或处于活动性进展状态的中枢神经系统（CNS）转移CNS病灶接受治疗且无症状的脑转移患者，如果符合以下所有标准，则有资格参加本研究： 1)符合RECISTv1.1定义的可测量病灶存在CNS之外； 2)患者无颅内出血或脊髓内出血病史； 3)患者在研究治疗开始前7天内未接受过立体定向放疗，在研究治疗开始前14天内未接受过全脑放射治疗，或在研究治疗开始前28天内未接受过神经外科切除术； 4)患者不需要持续接受皮质类固醇治疗中CNS疾病。允许接受稳定剂量的抗惊厥药物治疗； 5)转移仅限于小脑或幕上区域（即未转移至中脑、脑桥、延髓或脊髓）； 6.接受过实体脏器或血液系统移植； 7.有临床症状的第三间隙积液需要反复引流，如经抽水或其他治疗仍无法控制的心包积液、胸腔积液和腹腔积液； 8.控制不佳的肿瘤相关疼痛：? 1）需要镇痛药的患者在入选本研究时已有稳定的止痛治疗方案； 2）对有症状且可接受姑息性放疗的病灶（例如骨转移或导致神经压迫的转移灶），应在入组前完成治疗。患者应该从放疗的影响中恢复。未要求最短恢复期； 3）在入组前应该酌情考虑对现在无症状但随着进一步生长可能会导致功能缺损或顽固性疼痛的转移病灶进行局部治疗（例如目前与脊髓压迫无关的硬膜外转移）； 9.控制不佳的或有症状的高钙血症（离子钙>1.5mmol/L，钙>12mg/dL或校正后的钙 超过ULN）； 10.在随机分组前14天内曾罹患过需要使用皮质类固醇（泼尼松或等效药物的日剂量＞10 mg）或其他免疫抑制药物进行全身治疗的任何疾病； 11.活动性自身免疫性疾病或可能复发的自身免疫性疾病病史； 12.筛选期进行的胸部CT扫描存在特发性肺纤维化、器质性肺炎(如闭塞性细支气管炎)，或非感染性肺炎病史的证据； 13.随机分组前4周内出现过严重感染，包括但不限于因感染并发症、菌血症或严重肺炎住院治疗； 14.随机分组前14天内需要接受全身性（口服或静脉注射）抗生素治疗的严重慢性或活动性感染（包括肺结核感染等）； 15.已知有人类免疫缺陷病毒（HIV）感染史（即 HIV 1/2 抗体阳性）；未经治疗的活动性乙型肝炎； 注：符合下列标准的乙肝受试者也符合入选条件：首次给药前 HBV 病毒载量必须<2000 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。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；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）； 16.首剂用药前≤5年并发其他恶性肿瘤，充分治疗的宫颈原位癌、基底细胞或鳞状上皮细胞皮肤癌、根治术后的局部前列腺癌、根治术后的导管原位癌除外（允许非转移性前列腺癌或乳腺癌的激素治疗）； 17.随机前28天内使用减毒活疫苗，或预计研究期间需要使用此种减毒活疫苗（随机前4周、治疗期间以及阿得贝利单抗末次给药后5个月内患者不允许接种流感减毒活疫苗）； 18.哺乳期妇女，育龄期妇女且不愿意避孕； 19.达到以下任何心血管疾病标准： 1)开始研究治疗前 3个月内发生包括纽约心脏病学会心脏疾病（II 级或更高）； 2)开始研究治疗前6个月内发生心肌炎、心肌梗死或脑血管事件在内的重大心血管疾病、不稳定性心律失常或不稳定性心绞痛； 3)随机之前≤6个月内曾出现症状性肺栓塞； 4)已知有冠状动脉疾病或左心室射血分数（LVEF）<40%的患者； 20.其他任何理由，研究者认为不合适参加试验的医院初诊（或复诊）的门诊（或住院）患者。

Exclusion criteria：

1. Allergic to the experimental drug; 2. Is currently participating in an interventional clinical study, or has received other investigational drugs or used investigational devices within 4 weeks prior to initial dosing; 3. Prior treatment with any T cell co-stimulation or immune checkpoint, including but not limited to cytotoxic Tlymphocyte-associated antigen-4, CTLA-4) inhibitors, PD-1 inhibitors, PD-L1/2 inhibitors, or other drugs that target T cells; 4. Symptomatic brain metastases; 5. Patients with untreated or active progressive central nervous system (CNS) metastases who are treated for CNS lesions and are asymptomatic are eligible to participate in this study if they meet all of the following criteria: 1) Measurable lesions that meet the definition of RECISTv1.1 exist outside the CNS; 2) The patient had no history of intracranial or spinal hemorrhage; 3) The patient had not received stereotactic radiation therapy within 7 days before the start of study therapy, whole-brain radiation therapy within 14 days before the start of study therapy, or neurosurgical resection within 28 days before the start of study therapy; 4) Patients do not require ongoing corticosteroid treatment for CNS disease. Acceptance of stable doses of anticonvulsant drugs; 5) Metastasis is limited to the cerebellar or supratentorial areas (i.e. not to the midbrain, pons, medulla oblongata, or spinal cord); 6. Received solid organ or blood system transplantation; 7. Third space effusion with clinical symptoms requires repeated drainage, such as pericardial effusion, pleural effusion and abdominal effusion that cannot be controlled by pumping or other treatment; 8. Poorly controlled tumor-related pain: ? 1) Patients in need of analgesics had a stable analgesic treatment regimen at the time of enrollment in this study; 2) For lesions that are symptomatic and acceptable for palliative radiotherapy (such as bone metastases or metastases that cause nerve compression), treatment should be completed before enrollment. Patients should recover from the effects of radiation therapy. No minimum recovery period is required; 3) Local treatment of metastases that are currently asymptomatic but may lead to functional impairment or intractable pain with further growth (e.g., epidural metastases not currently associated with spinal cord compression) should be considered before enrollment, as appropriate; 9. Poorly controlled or symptomatic hypercalcemia (ionic calcium >1.5mmol/L, calcium >12mg/dL or corrected calcium) More than ULN); 10. Had any medical condition requiring systemic treatment with corticosteroids (prednisone or equivalent at a daily dose of > 10 mg) or other immunosuppressive agents during the 14 days prior to randomization; 11. A history of active autoimmune disease or autoimmune disease that may recur; 12. Evidence of a history of idiopathic pulmonary fibrosis, organic pneumonia (e.g., bronchiolitis obliterans), or noninfectious pneumonia on chest CT scans performed during the screening period; 13. A history of serious infections in the 4 weeks prior to randomization, including but not limited to hospitalization for infectious complications, bacteremia, or severe pneumonia; 14. Severe chronic or active infections (including tuberculosis infections, etc.) requiring systemic (oral or intravenous) antibiotic treatment within 14 days prior to randomization; 15. Known history of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2 antibody positive); Untreated active hepatitis B; Note: Hepatitis B subjects who met the following criteria were also eligible for inclusion: HBV viral load prior to initial dosing must be <2000 copies /ml (200 IU/ml), and subjects should receive anti-HBV therapy to avoid viral reactivation throughout study chemotherapy therapy. Subjects with anti-HBC (+), HBsAg (-), anti-HBS (-) and HBV viral load (-) do not need to receive prophylactic anti-HBV therapy, but need to closely monitor viral reactivation. Active HCV-infected subjects (HCV antibody positive and HCV-RNA levels above the lower limit of detection); 16. Other malignancies developed less than 5 years before the first dose, except for fully treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery, and ductal carcinoma in situ after radical surgery (hormone therapy for non-metastatic prostate cancer or breast cancer is allowed); 17. Use of live attenuated vaccine within 28 days prior to randomization, or anticipated use of such live attenuated vaccine during the study period (patients are not allowed to receive live attenuated influenza vaccine 4 weeks prior to randomization, during treatment, and 5 months after the final administration of adbelizumab); 18. Lactating women, women of childbearing age and do not want to use contraception; 19. Meet any of the following cardiovascular disease criteria: 1) Occurrence of heart disease (grade II or higher) within 3 months prior to the start of study treatment includes the New York College of Cardiology; 2) Major cardiovascular disease, unstable arrhythmia, or unstable angina, including myocarditis, myocardial infarction, or cerebrovascular events, occurring within 6 months before the start of study treatment; 3) Symptomatic pulmonary embolism occurred within 6 months prior to randomization; 4) Patients with known coronary artery disease or left ventricular ejection fraction (LVEF) <40%; 20. Outpatient (or inpatient) patients who were newly admitted (or returned) to the hospital for any other reason that the investigator considered inappropriate to participate in the trial.

研究实施时间：

Study execute time：

从 From 2024-01-01 00:00:00至 To 2024-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2024-01-01 00:00:00 至 To 2024-12-31 00:00:00  

干预措施：

Interventions：

组别：

试验组

样本量：

50

Group：

Experimental group

Sample size：

干预措施：

阿得贝利单抗+卡铂+依托泊苷+放疗

干预措施代码：

Intervention：

Adebrelimab+carboplatin+etoposide+radiotherapy

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 湖南 

市(区县)：

 长沙 

Country：

China 

Province：

Hunan 

City：

Changsha 

单位(医院)：

湖南省肿瘤医院 

单位级别：

三甲 

Institution
hospital：

Hunan 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：

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：

mPFS

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：

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：

缓解持续时间

指标类型：

次要指标

Outcome：

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：

疾病控制率

指标类型：

次要指标

Outcome：

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：

SCLC-A/N/P/I 四种转录因子亚型、PD-L1 的表达与疗效的关系

指标类型：

次要指标

Outcome：

The relationship between the expression of four transcription factor subtypes of SCLC-A/N/P/I, PD-L1, and therapeutic efficacy

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：

无

组织：

Sample Name：

NO

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 100 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）：

Calculated Results after
the Study Completed(upload file)：

是否共享原始数据：

IPD sharing

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）：

无

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

No

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：

无

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

No

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：

  2023-12-26 10:35:56