中国临床试验注册中心 - 世界卫生组织国际临床试验注册平台一级注册机构

注册号： Registration number：	ChiCTR2600116503
最近更新日期： Date of Last Refreshed on：	2026-01-12 10:09:45
注册时间： Date of Registration：	2026-01-12 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	阿美替尼联合酒石酸长春瑞滨软胶囊治疗三代EGFR-TKI经治进展晚期NSCLC老年患者的开放、单臂、探索性Ⅱ期临床研究
Public title：	An Open-Label, Single-Arm, Exploratory Phase Ⅱ Clinical Study of Almonertinib Combined with Vinorelbine Tartrate Soft Capsules in the Treatment of Elderly Patients with Advanced NSCLC Progressed after Third-Generation EGFR-TKI Therapy
注册题目简写：
English Acronym：
研究课题的正式科学名称：	阿美替尼联合酒石酸长春瑞滨软胶囊治疗三代EGFR-TKI经治进展晚期NSCLC老年患者的开放、单臂、探索性Ⅱ期临床研究
Scientific title：	An Open-Label, Single-Arm, Exploratory Phase Ⅱ Clinical Study of Almonertinib Combined with Vinorelbine Tartrate Soft Capsules in the Treatment of Elderly Patients with Advanced NSCLC Progressed after Third-Generation EGFR-TKI Therapy
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：	王姗姗	研究负责人：	刘东颖
Applicant：	Shanshan Wang	Study leader：	Dongying Liu
申请注册联系人电话： Applicant telephone：	+86 188 1056 6533	研究负责人电话： Study leader's telephone：	+86 153 3200 6050
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：	cfdyn8969@126.com	研究负责人电子邮件： Study leader's E-mail：	ldytjnk@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：	中国天津市河西区体院北环湖西路	研究负责人通讯地址：	中国天津市河西区体院北环湖西路
Applicant address：	Huanhu West Road, Tiyuanbei Area, Hexi District, Tianjin	Study leader's address：	Huanhu West Road, Tiyuanbei Area, Hexi District, Tianjin
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：	天津市肿瘤医院
Applicant's institution：	Tianjin Medical University Cancer Institute and Hospital
研究负责人所在单位：	天津市肿瘤医院
Affiliation of the Leader：	Tianjin Medical University Cancer Institute and Hospital

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：	E20251310	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：	天津市肿瘤医院医学伦理委员会
Name of the ethic committee：	Medical Ethics Committee of Tianjin Medical University Cancer Institute and Hospital
伦理委员会批准日期： Date of approved by ethic committee：	2025-12-03 00:00:00
伦理委员会联系人：	刘美君
Contact Name of the ethic committee：	Meijun Liu
伦理委员会联系地址：	中国天津市河西区体院北环湖西路
Contact Address of the ethic committee：	Huanhu West Road, Tiyuanbei Area, Hexi District, Tianjin, China
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 23 340 123 6417	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：

天津市肿瘤医院

Primary sponsor：

Tianjin Medical University Cancer Institute and Hospital

研究实施负责（组长）单位地址：

中国天津市河西区体院北环湖西路

Primary sponsor's address：

Huanhu West Road, Tiyuanbei Area, Hexi District, Tianjin, 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)：	天津	市(区县)：
Country：	China	Province：	Tianjin	City：
单位(医院)：	天津市肿瘤医院	具体地址：	中国天津市河西区体院北环湖西路
Institution hospital：	Tianjin Medical University Cancer Institute and Hospital	Address：	Huanhu West Road, Tiyuanbei Area, Hexi District, Tianjin, China

经费或物资来源：

北京惠康仁爱基金会

Source(s) of funding：

Beijing Huikang Ren'ai Foundation

研究疾病：

非小细胞肺癌

Target disease：

Non-small cell lung cancer

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：

II期临床试验

Study phase：

2

研究设计：

单臂

Study design：

Single arm

研究目的：

主要研究目的：探索阿美替尼联合酒石酸长春瑞滨软胶囊治疗三代EGFR-TKI经治进展晚期非小细胞肺癌（NSCLC）老年患者的中位无进展生存期（Progression-Free-Survival，PFS）次要研究目的： 1.探索阿美替尼联合酒石酸长春瑞滨软胶囊治疗三代EGFR-TKI经治进展晚期NSCLC老年患者的中位总生存期（OS）；客观缓解率（ORR）、疾病控制率（DCR）、缓解持续时间（DoR） 2.探索阿美替尼联合酒石酸长春瑞滨软胶囊治疗三代EGFR-TKI经治进展晚期NSCLC老年患者的安全性分析和健康相关生活质量评价（QOL/FACT-L）探索性目的： 1.阿美替尼联合酒石酸长春瑞滨软胶囊治疗三代EGFR-TKI经治进展晚期NSCLC老年患者的细分人群亚组分析（脑转移/突变类型/共突变等）与疗效相关性 2.阿美替尼联合酒石酸长春瑞滨软胶囊治疗三代EGFR-TKI经治进展晚期NSCLC老年患者的药物经济性分析

Objectives of Study：

Primary Objective To explore the median progression-free survival (PFS) of almonertinib combined with vinorelbine tartrate soft capsules in the treatment of elderly patients with advanced non-small cell lung cancer (NSCLC) who progressed after third-generation EGFR-TKI therapy. Secondary Objectives 1.To explore the median overall survival (OS), objective response rate (ORR), disease control rate (DCR) and duration of response (DoR) of almonertinib combined with vinorelbine tartrate soft capsules in the treatment of elderly patients with advanced NSCLC who progressed after third-generation EGFR-TKI therapy. 2.To evaluate the safety profile and health-related quality of life (QOL/FACT-L) of almonertinib combined with vinorelbine tartrate soft capsules in the treatment of elderly patients with advanced NSCLC who progressed after third-generation EGFR-TKI therapy. Exploratory Objectives 1.To investigate the correlation between subgroup analysis (brain metastasis/mutation type/co-mutation, etc.) and therapeutic efficacy of almonertinib combined with vinorelbine tartrate soft capsules in elderly patients with advanced NSCLC who progressed after third-generation EGFR-TKI therapy. 2.To conduct a pharmacoeconomic analysis of almonertinib combined with vinorelbine tartrate soft capsules in the treatment of elderly patients with advanced NSCLC who progressed after third-generation EGFR-TKI therapy.

药物成份或治疗方案详述：

Description for medicine or protocol of treatment in detail：

纳入标准：

Inclusion criteria

1.Histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR-sensitive mutations (19del and L858R) confirmed by tissue or blood-based genetic testing.
2.Documented disease progression (local or systemic progression) following prior treatment with a third-generation EGFR-TKI, and all toxic reactions induced by prior treatments have resolved to <= Grade 1 according to the CTCAE v4.0 criteria (alopecia is excluded).
3.Elderly male or female subjects aged >= 65 years who have signed the informed consent form.
4.Subjects with asymptomatic brain metastases or brain metastases under stable control.
5.ECOG performance status score of 0–3 and an expected survival of more than 3 months.
6.Subjects must undergo tissue or blood sample genetic testing to confirm mutation type after enrollment; alternatively, subjects who are unable to undergo sample testing due to objective reasons may be enrolled for treatment after clinical evaluation and judgment by the investigators.
7.Normal function of major organs, defined as meeting the following laboratory criteria:
(1) Hematological criteria (no blood transfusion, blood products, G-CSF or other hematopoietic stimulants administered within 14 days prior to testing):
a. Hemoglobin >= 90 g/L;
b. Absolute neutrophil count (ANC) >= 1.5×10^9/L;
c. Platelet count >= 100×10^9/L.
(2) Biochemical criteria:
a. Total bilirubin < 1.5 × upper limit of normal (ULN);
b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 × ULN; for patients with liver metastases, AST and ALT < 5 × ULN;
c. Serum creatinine (Cr) <= 1.5 × ULN **or** calculated creatinine clearance rate (Ccr) > 25 mL/min (using the Cockcroft-Gault formula).
8.Women of childbearing potential must use adequate contraceptive measures from screening until 3 months after discontinuation of study treatment and must not breastfeed. A negative pregnancy test result is required prior to the first dose of study treatment, or subjects must meet one of the following criteria to confirm no pregnancy risk:
a. Postmenopausal status, defined as aged > 50 years with amenorrhea for at least 12 consecutive months without exogenous hormone replacement therapy;
b. For women aged < 50 years, postmenopausal status can also be confirmed if they have had amenorrhea for at least 12 consecutive months without exogenous hormone replacement therapy and their luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels are within the postmenopausal reference range of the testing laboratory;
c. History of irreversible sterilization surgery, including hysterectomy, bilateral oophorectomy or bilateral salpingectomy (bilateral tubal ligation is excluded).
9.Male subjects must use barrier contraception (i.e., condoms) from screening until 3 months after discontinuation of study treatment.
10.Subjects voluntarily agree to participate in this study, are able to communicate effectively with investigators, and can comply with the study requirements including scheduled visits, treatment administration, laboratory tests and other related procedures.

排除标准：

1.混合型肺癌若存在小细胞癌、神经内分泌癌、肉瘤成分则不可以入组； 2.治疗开始时有严重症状的脑转移患者； 3.经组织或血液样本基因检测发现患者出现除EGFR突变外的其他耐药突变（如MET扩展等） 4.患者拒绝接受本研究的治疗方案 5.病史或合并症： a.症状明显的脑转移、癌性脑膜炎、脊髓压迫患者，或筛选时影像学CT 或MRI 检查发现脑或软脑膜的疾病（入组前14天已完成治疗且症状稳定的脑转移患者可以入组，但需经颅脑MRI、CT或静脉造影评价确认为无脑出血症状）； b.患者正在参加其他临床研究或距离前一项临床研究治疗结束时间不足4周； c.需要同时治疗的其他活动性恶性肿瘤； d.具有其他恶性肿瘤史（除外经有效治疗的非黑色素瘤皮肤癌、原位癌或经治疗后＞5年无任何疾病证据的其他实体瘤）； e.有间质性肺病病史、药物性间质性肺病病史、需要类固醇治疗的放射性肺炎病史或有临床活动性间质性肺病的任何证据； f.凝血功能异常（凝血酶原时间国际标准化比值INR>1.5或凝血酶原时间PT>ULN+4秒或APTT >1.5 ULN），具有出血倾向或正在接受溶栓或抗凝治疗；注：在INR≤ 1.5的前提下，允许以预防目的使用小剂量肝素（成人每日用量为0.6万~1.2万U）或小剂量阿司匹林（每日用量≤ 100 mg）； g. 需要全身治疗的严重急性或慢性感染； h.符合以下任一一项心脏检查结果：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）；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）；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；左心室射血分数（LVEF）≤40%； i.失代偿性糖尿病或存在大剂量糖皮质激素治疗的其它禁症； j.具有明显影响口服药物吸收的因素，如难治性恶心，呕吐或慢性胃肠道疾病，不能吞咽研究药物或曾接受大范围的肠切除术等；开始治疗前6个月内有气管-食管瘘、胃肠穿孔或胃肠瘘以及腹腔内脓肿病史者； k.入组前3个月内出现临床显著的咯血（每日咯血大于50ml）；或显著临床意义的出血症状或具有明确的出血倾向，如消化道出血、出血性胃溃疡、基线期大便潜血++及以上等； l.入组前12个月内发生动/静脉血栓事件，如脑血管意外（包括暂时性缺血性发作、脑出血、脑梗塞）、深静脉血栓及肺栓塞等； m.使用两种或两种以上联合治疗仍无法控制的高血压（收缩压≥140 mmHg或者舒张压≥90 mmHg）； n.具有精神类药物滥用史且无法戒除或者有精神障碍的； 5.哺乳期或者研究治疗首次给药前3天内血或尿妊娠试验结果阳性的女性； 6.对阿美替尼的任何活性或非活性成分或对与阿美替尼化学结构类似或阿美替尼同类别的药物有超敏反应史； 7.对长春瑞滨或其辅料过敏者或禁忌者； 8.任何严重或者未控制的眼部病变，经医生判断可能增加患者的安全性风险； 9.查体和实验室检查所见：已知有人类免疫缺陷病毒（HIV）检查阳性病史或已知有获得性免疫缺陷综合征（艾滋病）；未经治疗的活动性肝炎（乙肝：HBsAg阳性且HBV DNA≥ 500IU/mL；丙肝：HCV RNA阳性且肝功能异常）；合并乙肝及丙肝共同感染； 10.经研究者判断，患者可能有其他可能导致本研究被迫中途终止的因素，如其他的严重疾病或严重的实验室检查异常或伴有其他会影响到受试者的安全，或试验资料及样品收集的家庭或社会等因素。

Exclusion criteria：

1.Mixed-type lung cancer with components of small cell carcinoma, neuroendocrine carcinoma, or sarcoma. 2.Patients with brain metastases presenting with severe symptoms at the initiation of treatment. 3.Detection of other drug-resistant mutations (e.g., MET amplification, etc.) besides EGFR mutations via tissue or blood-based genetic testing. 4.Patients who refuse to receive the treatment regimen specified in this study. 5.Medical history or comorbidities: a. Patients with symptomatic brain metastases, carcinomatous meningitis, or spinal cord compression; or those with radiologically confirmed brain or leptomeningeal lesions on CT or MRI at screening (patients with brain metastases who have completed treatment and achieved stable symptoms within 14 days prior to enrollment may be eligible, provided that cranial MRI, CT or venography confirms the absence of cerebral hemorrhage symptoms). b. Patients who are currently participating in other clinical studies or whose interval from the end of treatment in the previous clinical study is less than 4 weeks. c. Presence of other active malignant tumors requiring concurrent treatment. d. History of other malignant tumors (excluding adequately treated non-melanoma skin cancer, carcinoma in situ, or other solid tumors with no evidence of disease for more than 5 years after treatment). e. History of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy, or any evidence of clinically active interstitial lung disease. f. Coagulopathy (international normalized ratio [INR] of prothrombin time > 1.5; prothrombin time [PT] > ULN + 4 seconds; or activated partial thromboplastin time [APTT] > 1.5 × ULN), bleeding tendency, or ongoing thrombolytic or anticoagulant therapy. Note: Low-dose heparin (daily dosage of 6,000–12,000 U for adults) or low-dose aspirin (daily dosage <= 100 mg) for prophylactic purposes is permitted provided that INR <= 1.5. g. Severe acute or chronic infections requiring systemic treatment. h. Any of the following abnormal cardiac examination findings: mean corrected QT interval (QTc) > 470 msec on three resting electrocardiograms (ECG), with QT interval correction using the Fridericia formula (QTcF); resting ECG showing clinically significant rhythm, conduction or morphological abnormalities (e.g., complete left bundle branch block, third-degree atrioventricular block, second-degree atrioventricular block, or PR interval > 250 msec); presence of any factors increasing the risk of QTc prolongation or arrhythmic events, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, unexplained sudden death in first-degree relatives under 40 years old, or concurrent use of any drugs that prolong QT interval; left ventricular ejection fraction (LVEF) <= 40%. i. Decompensated diabetes mellitus or other contraindications for high-dose glucocorticoid therapy. j. Factors significantly impairing oral drug absorption, such as refractory nausea, vomiting, chronic gastrointestinal diseases, inability to swallow study drugs, or history of extensive intestinal resection; history of tracheoesophageal fistula, gastrointestinal perforation, gastrointestinal fistula, or intra-abdominal abscess within 6 months prior to treatment initiation. k. Clinically significant hemoptysis (daily hemoptysis > 50 mL) within 3 months prior to enrollment; or clinically significant bleeding symptoms or definite bleeding tendency (e.g., gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood test ++ or above, etc.). l. History of arterial/venous thrombotic events (e.g., cerebrovascular accident including transient ischemic attack, cerebral hemorrhage, cerebral infarction; deep vein thrombosis; pulmonary embolism, etc.) within 12 months prior to enrollment. m. Uncontrolled hypertension despite treatment with two or more antihypertensive agents in combination (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg). n. History of psychoactive substance abuse with inability to abstain, or presence of mental disorders. 5.Lactating women or women with positive blood or urine pregnancy test results within 3 days prior to the first administration of study treatment. 6.History of hypersensitivity to any active or inactive ingredients of almonertinib, or to drugs with similar chemical structures or belonging to the same class as almonertinib. 7.Hypersensitivity or contraindication to vinorelbine or its excipients. 8.Any severe or uncontrolled ophthalmic disorders that may increase the patient’s safety risk as judged by a physician. 9.Findings from physical examination and laboratory tests: known history of positive human immunodeficiency virus (HIV) test or acquired immunodeficiency syndrome (AIDS); untreated active viral hepatitis (hepatitis B: HBsAg-positive with HBV DNA >= 500 IU/mL; hepatitis C: HCV RNA-positive with abnormal liver function); concurrent hepatitis B and C coinfection. 10.Any other factors judged by the investigator that may result in premature termination of the study for the patient, such as other severe diseases, significant laboratory abnormalities, or family/social factors that may affect the subject’s safety or the collection of trial data and samples.

研究实施时间：

Study execute time：

从 From 2025-10-01 00:00:00至 To 2026-12-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2026-01-31 00:00:00 至 To 2026-12-31 00:00:00

干预措施：

Interventions：

组别：	治疗组	样本量：	100
Group：	Treatment Group	Sample size：	100
干预措施：	阿美替尼联合酒石酸长春瑞滨软胶囊	干预措施代码：
Intervention：	Almonertinib Combined with Vinorelbine Tartrate Soft Capsules	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	天津	市(区县)：
Country：	China	Province：	Tianjin	City：
单位(医院)：	天津市肿瘤医院	单位级别：	三甲
Institution hospital：	Tianjin Medical University Cancer Institute and Hospital	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	中位无进展生存期	指标类型：	主要指标
Outcome：	Progression-Free-Survival,PFS	Type：	Primary 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：	客观缓解率	指标类型：	次要指标
Outcome：	Objective response rate, ORR	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 Response, DoR	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	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	65	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:

公开/Public

盲法：
Blinding：
试验完成后的统计结果（上传文件）：	点击下载
Calculated Results after the Study Completed(upload file)：	download

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）：	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, CRF
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：	2026-01-12 10:09:39