今天是:2022-08-12 星期五

该研究未获得伦理委员会批准,请于批准后开始征募参试者,并与我们联系上传伦理批件。 派安普利单抗联合甲磺酸仑伐替尼用于晚期肝癌一线治疗的探索性研究
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注册号:

Registration number:

ChiCTR2200061888 

最近更新日期:

Date of Last Refreshed on:

2022-07-06 

注册时间:

Date of Registration:

2022-07-06 

注册号状态:

预注册  

Registration Status:

Prospective registration  

注册题目:

该研究未获得伦理委员会批准,请于批准后开始征募参试者,并与我们联系上传伦理批件。 派安普利单抗联合甲磺酸仑伐替尼用于晚期肝癌一线治疗的探索性研究 

Public title:

An exploratory study of pembrolizumab combined with lenvatinib mesylate for first-line treatment of advanced hepatocellular carcinoma 

注册题目简写:

派安普利单抗联合仑伐替尼一线治疗晚期肝癌的RWS 

English Acronym:

A RWS that Pienpilimumab combined with lenvatinib in first-line treatment advanced hepatocellular carcinoma 

研究课题的正式科学名称:

派安普利单抗联合甲磺酸仑伐替尼用于晚期肝癌一线治疗的探索性研究 

Scientific title:

An exploratory study of pembrolizumab combined with lenvatinib mesylate for first-line treatment of advanced hepatocellular carcinoma 

研究课题代号(代码):

Study subject ID:

TQXB-H-002 

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:

陈安 

研究负责人:

陈安 

Applicant:

An Chen 

Study leader:

An Chen 

申请注册联系人电话:

Applicant telephone:

187 9299 7900 

研究负责人电话:

Study leader's telephone:

187 9299 7900 

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:

chenfeng282128@163.com 

研究负责人电子邮件:

Study leader's E-mail:

chenfeng282128@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:

陕西省西安市灞桥区空军军医大学唐都医院 

研究负责人通讯地址:

陕西省西安市灞桥区空军军医大学唐都医院 

Applicant address:

Tangdu Hospital, Air Force Military Medical University, Baqiao District, Xi'an City, Shaanxi Province 

Study leader's address:

Tangdu Hospital, Air Force Military Medical University, Baqiao District, Xi'an City, Shaanxi Province 

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:

空军军医大学唐都医院 

Applicant's institution:

Tangdu Hospital, Air Force Military Medical University 

是否获伦理委员会批准:

否 

Approved by ethic committee:

NO 

伦理委员会批件文号:

Approved No. of ethic committee:

 

伦理委员会批件附件:

Approved file of Ethical Committee:

批准本研究的伦理委员会名称:

 

Name of the ethic committee:

 

伦理委员会批准日期:

Date of approved by ethic committee:

2013-08-26 

伦理委员会联系人:

 

Contact Name of the ethic committee:

 

伦理委员会联系地址:

 

Contact Address of the ethic committee:

 

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:

空军军医大学唐都医院 

Primary sponsor:

Tangdu Hospital, Air Force Military Medical University 

研究实施负责(组长)单位地址:

陕西省西安市灞桥区空军军医大学唐都医院 

Primary sponsor's address:

Tangdu Hospital, Air Force Military Medical University, Baqiao District, Xi'an City, Shaanxi Province 

试验主办单位(项目批准或申办者):

Secondary sponsor:

国家:

中国

省(直辖市):

陕西省

市(区县):

Country:

China

Province:

Shaanxi

City:

单位(医院):

空军军医大学唐都医院

具体地址:

陕西省西安市灞桥区空军军医大学唐都医院

Institution
hospital:

Tangdu Hospital, Air Force Military Medical University

Address:

Tangdu Hospital, Air Force Military Medical University, Baqiao District, Xi'an City, Shaanxi Province

经费或物资来源:

自筹 

Source(s) of funding:

self-funded 

研究疾病:

肝细胞癌 

Target disease:

hepatocellular carcinoma 

研究疾病代码:

 

Target disease code:

 

研究类型:

观察性研究 

Study type:

Observational study 

研究所处阶段:

上市后药物 

Study phase:

研究目的:

观察和评价派安普利单抗联合甲磺酸仑伐替尼用于晚期肝癌 一线治疗的临床有效性及药物安全性。 

Objectives of Study:

To observe and evaluate the clinical efficacy and drug safety of pembrolizumab combined with lenvatinib mesylate in the first-line treatment of advanced liver cancer 

药物成份或治疗方案详述:

 

Description for medicine or protocol of treatment in detail:

 

研究设计:

单臂 

Study design:

Single arm 

纳入标准:

1. 年龄≥18 岁; 2. ECOG 评分:0-2 分; 3. 组织学或细胞学确认的肝细胞癌(HCC)受试者; 4. BCLC 分期为 C 期或不适合根治性手术和/或局部治疗的 B 期;或经过手术和/或局部治疗后进展; 5. 局部治疗后进展的患者,局部治疗(包括但不限于手术、 放疗、肝动脉栓塞、 TACE、肝动脉灌注、射频消融、冷 冻消融或经皮乙醇注射)至少在基线影像学扫描前 4 周 已完成, 且局部治疗引起的毒性反应(脱发除外) 必须恢 复至美国国家癌症研究所-不良事件通用术语标准第 5.0 版(NCI-CTCAE v5.0)评级≤1 级; 6. Child-Pugh A 级; 7. 至少有一个由研究者根据 RECIST v1. 1 可测量的未治疗 病灶, 螺旋计算机断层(CT) 增强扫描病灶 ≥10 mm 或 对比增强磁共振成像(MRI) 扫描病灶≥10mm (恶性淋 巴结短径必须 ≥15 mm); 8. 预计生存期≥12 周; 9. 先前未接受过系统性 HCC 治疗(包括: 化疗, 索拉非尼、 瑞格非尼、仑伐替尼或其他小分子抗血管生成药物,抗 PD- 1/PD-L1 抗体、抗 PD-L2 抗体、抗 CD137 抗体、 抗 CTLA-4 抗体或其他作用于 T 细胞共刺激或检查点 通路的药物/抗体等),但不包括接受过辅助治疗; 10. 育龄期女性、伴侣为育龄期女性的男性受试者, 必须同意在签署知情同意书后、研究期间及研究药物最后一次给 药后至少 6 个月内采取有效避孕措施。具体避孕措施及 育龄女性定义见附件 5 避孕措施、育龄女性的定义和避 孕要求; 11,充分控制的血压, 指筛选期收缩压≤150 mmHg 且舒张压 ≤90 mmHg,且如果有抗高血压药物治疗, 研究药物首 次用药前一周内需未改变过处方; 12,肝肾功能需符合: a. TBIL≤1.5 ULN; b. ALT 和 AST≤5 ULN; c.血清肌酐≤1.5ULN (或肌酐清除率≥40 mL/min/1.73 m2 ); 13,血常规检查标准需符合(14 天内未输血及血制品,未使 用 G-CSF 及其他造血刺激因子纠正): a. HB≥9.0 g/dL; b. ANC≥1.5×109 /L; c. PTL≥100×109 /L; 14, 自愿参加临床研究; 完全了解、知情本研究并签署知情同 意书(Informed Consent Form,ICF);愿意遵循并有能力 完成所有研究程序; 15,研究者判断可参加本临床试验。 

Inclusion criteria

1. Age ≥18 years; 2. ECOG score: 0-2; 3. Histologically or cytologically confirmed hepatocellular carcinoma (HCC) subjects; 4. BCLC stage C or not suitable for radical surgery and Stage B of local therapy; or progression after surgery and/or local therapy; 5. Patients who progressed after local therapy, local therapy (including but not limited to surgery, radiotherapy, hepatic artery embolization, TACE, hepatic artery perfusion, radiofrequency Ablation, cryoablation, or percutaneous ethanol injection) completed at least 4 weeks prior to baseline imaging scan, and localized therapy-induced toxicity (other than alopecia) must be reverted to the National Cancer Institute-General Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0) grade ≤1; 6. Child-Pugh A; 7. At least one untreated lesion measurable by investigator according to RECIST v1.1, helical computed tomography (CT)-enhanced lesion ≥10 mm or contrast-enhanced magnetic resonance imaging (MRI) scan lesions ≥10 mm (malignant lymph nodes must be ≥15 mm in short diameter); 8. Expected survival ≥12 weeks; 9. No prior systemic HCC treatment (including: chemotherapy , sorafenib, regorafenib, lenvatinib or other small molecule anti-angiogenic drugs, anti-PD-1/PD-L1 antibody, anti-PD-L2 antibody, anti-CD137 antibody, anti-CTLA-4 antibody or Other drugs/antibodies acting on T-cell co-stimulation or checkpoint pathways, etc.), but not including adjuvant therapy; 10. Females of childbearing age and male subjects whose partners are females of childbearing age must agree to sign the informed consent form Use effective contraception during the study period and for at least 6 months after the last dose of study drug. For specific contraceptive measures and definitions of women of childbearing age, see Annex 5. Contraceptive measures, definitions of women of childbearing age, and contraceptive requirements; 11. Adequately controlled blood pressure refers to systolic blood pressure ≤150 mmHg and diastolic blood pressure ≤90 mmHg during the screening period, and if antihypertensive drugs are available 12. Liver and kidney function must meet: a. TBIL≤1.5 ULN; b. ALT and AST≤5 ULN; c. Serum creatinine≤1.5ULN (or creatinine clearance rate ≥40 mL/min/1.73 m2); 13. The blood routine examination standards must be met (no blood transfusion and blood products within 14 days, no correction with G-CSF and other hematopoietic stimulating factors): a. HB≥9.0 g/dL; b . ANC≥1.5×109/L; c. PTL≥100×109/L; 14. Voluntarily participate in clinical research; fully understand and understand this research and sign the Informed Consent Form (ICF); willing to follow and have the ability Complete all research procedures; 15. The investigator judges that they can participate in this clinical trial. 

排除标准:

1, 已知肝胆管细胞癌、肉瘤样 HCC、混合细胞癌及纤维板层细胞癌; 5 年内或同时患有除 HCC 之外的其它活动性 恶性肿瘤。已治愈的局限性肿瘤, 如皮肤基底细胞癌、皮 肤鳞癌、表浅膀胱癌、前列腺原位癌、宫颈原位癌、乳腺 原位癌等可以入组; 2, 已知对试验药物或其它任何辅料过敏; 或者对其他单克隆抗体发生过严重过敏反应。 3. 研究治疗开始前一周内接受过中药治疗(说明书有明确抗 肿瘤的适应症); 4. 入组前两周内服用免疫抑制药物; 5. 每日口服用量超过 10mg 强的松或等剂量激素; 6. 入组前两周需要抗菌药物治疗的严重感染; 7. 存在任何活动性自身免疫病或有自身免疫病病史且预期 复发(包括但不局限于: 自身免疫性肝炎、间质性肺炎、 葡萄膜炎、肠炎、肝炎、垂体炎、血管炎、肾炎、甲状腺 功能亢进、甲状腺功能降低[仅通过激素替代治疗可以控 制的受试者可纳入];受试者患有无需全身治疗的皮肤病 如白癜风、银屑病、脱发、 I 型糖尿病或在童年期哮喘已 完全缓解, 成人后无需任何干预的可纳入; 需要支气管扩 张剂进行医学干预的哮喘患者则不能纳入); 8. 研究药物首次用药之前 6 个月内, 曾出现重大血管疾病 (例如,需要手术修补或近期有外周动脉血栓形成的主 动脉瘤),或曾出现门静脉高压伴随消化道出血;或有 CTCAE 3 级及以上出血事件;或 3 个月内有 2 级出血事 件;或筛选时有出血的表现(包括咯血、异常阴道流血 等);研究药物首次用药之前 3 个月内有胃/食管静脉曲张 需要医学干预的受试者; 9. 研究药物首次用药之前 6 个月内出现脑血管意外、心肌梗 塞、不稳定心绞痛、控制不良的心律失常(包括 QTc 间 期> 480 ms ,QTc 间期以 Fridericia 公式计算); 10. 研究药物首次用药之前 6 个月内曾出现腹部或气管食管 瘘、胃肠道(GI)穿孔或腹内脓肿;肠梗阻和/或曾有胃 肠道梗阻临床体征或症状,包括与原有疾病有关或需要 常规肠外水化、肠外营养或管饲的不完全梗阻; 腹内炎性 过程,包括但不限于消化性溃疡、憩室炎或结肠炎; 11,肝性脑病病史;或既往曾出现高血压危象或高血压性脑 病; 12, 既往和目前有间质性肺炎、尘肺、放射性肺炎、药物相关肺炎、肺功能严重受损等可能会干扰可疑的药物相关肺 毒性的检测和处理的受试者; 13,受试者存在免疫缺陷性疾病或病史,或有器官移植史; 14,怀孕或哺乳期妇女; 15,存在其他严重身体或精神疾病或实验室检查异常, 可能增 加参与研究的风险, 或干扰研究结果, 以及研究者认为不适合参与本研究的患者; 

Exclusion criteria:

1. Known hepatocholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma and fibrolamellar cell carcinoma; other active malignancies other than HCC within 5 years or at the same time. Localized tumors that have been cured, such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, prostate carcinoma in situ, cervical carcinoma in situ, breast carcinoma in situ, etc. can be included in the group; Allergy to any excipient; or severe allergic reaction to other monoclonal antibodies. 3. Received traditional Chinese medicine treatment within one week before the start of study treatment (the instructions have clear indications for anti-tumor); 4. Take immunosuppressive drugs within two weeks before enrollment; 5. Daily oral dose of prednisone exceeds 10mg or equivalent dose Hormones; 6. Serious infections requiring antimicrobial therapy two weeks before enrollment; 7. Any active autoimmune disease or history of autoimmune disease and expected recurrence (including but not limited to: autoimmune hepatitis, interstitial Pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism [subjects controlled by hormone replacement therapy only]; subjects with Skin diseases such as vitiligo, psoriasis, alopecia, type I diabetes, or asthma that has been completely resolved in childhood without any intervention in adulthood can be included; patients with asthma who require medical intervention with bronchodilators are not included); 8. Research Major vascular disease (eg, aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis), or portal hypertension with gastrointestinal bleeding within 6 months prior to the first dose of the drug; or CTCAE grade 3 or higher Bleeding events; or grade 2 bleeding events within 3 months; or bleeding manifestations at screening (including hemoptysis, abnormal vaginal bleeding, etc.); gastric/esophageal varices within 3 months prior to the first dose of study drug requiring medical intervention Subjects; 9. Cerebrovascular accident, myocardial infarction, unstable angina pectoris, poorly controlled arrhythmia (including QTc interval > 480 ms, QTc interval calculated by Fridericia formula) within 6 months before the first administration of the study drug; 10. Abdominal or tracheoesophageal fistula, gastrointestinal (GI) perforation or intra-abdominal abscess within 6 months prior to the first dose of study drug; intestinal obstruction and/or clinical signs or symptoms of gastrointestinal obstruction, including Disease-related or incomplete obstruction requiring routine parenteral hydration, parenteral nutrition, or tube feeding; Intra-abdominal inflammatory processes, including but not limited to peptic ulcers, diverticulitis, or colitis; 11. History of hepatic encephalopathy; or Hypertensive crisis or hypertensive encephalopathy has occurred in the past; 12. Past and current interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, severely impaired lung function, etc. may interfere with the detection of suspected drug-related pulmonary toxicity and treated subjects; 13. Subjects with immunodeficiency diseases or medical history, or with a history of organ transplantation; 14. Pregnant or lactating women; 15. There are other serious physical or mental illnesses or laboratory abnormalities, possibly increase the risk of participating in the study, or interfere with the results of the study, and patients who the investigator considers unsuitable to participate in this study; 

研究实施时间:

Study execute time:

From2022-07-05To 2024-07-05 

征募观察对象时间:

Recruiting time:

From2022-07-05To 2024-07-05 

干预措施:

Interventions:

组别:

实验组

样本量:

43

Group:

test group

Sample size:

干预措施:

派安普利单抗联合仑伐替尼

干预措施代码:

Intervention:

Pembrolizumab in combination with lenvatinib

Intervention code:

研究实施地点:

Countries of recruitment and research settings:

国家:

中国 

省(直辖市):

陕西省 

市(区县):

 

Country:

China 

Province:

Shaanxi 

City:

 

单位(医院):

空军军医大学唐都医院 

单位级别:

三级甲等 

Institution
hospital:

Tangdu Hospital, Air Force Military Medical University  

Level of the institution:

tertiary first class 

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:

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:

疾病进展时间

指标类型:

次要指标 

Outcome:

TTP

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:

客观缓解持续时间

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:

12 个月生存率

指标类型:

次要指标 

Outcome:

12mOS

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:

组织:

Sample Name:

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 years
最大 Max age 75 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):

单臂试验无需随机

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

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

否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):

do not share

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:

CRF

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:

 2022-07-06
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