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：	ChiCTR2500110037
最近更新日期： Date of Last Refreshed on：	2025-09-29 10:24:57
注册时间： Date of Registration：	2025-09-29 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	肺腺癌难治性柔脑膜转移患者培美曲塞鞘内化疗同步放疗伴后续长周期鞘内化疗的单中心、随机、优效性II期临床研究
Public title：	A single-center, randomized, phase II superiority clinical trial of concurrent radiotherapy and intrathecal pemetrexed followed by long-term intrathecal maintenance chemotherapy in patients with refractory leptomeningeal metastases from lung adenocarcinoma
注册题目简写：
English Acronym：
研究课题的正式科学名称：	肺腺癌难治性柔脑膜转移患者培美曲塞鞘内化疗同步放疗伴后续长周期鞘内化疗的单中心、随机、优效性II期临床研究
Scientific title：	A Single-Center, Randomized, Superiority Phase II Clinical Study of Intrathecal Pemetrexed Chemotherapy with Concurrent Radiotherapy Followed by Long-Term Intrathecal Maintenance therapy in Patients with Refractory Leptomeningeal Metastases from Non-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：	陈群	研究负责人：	徐庆生
Applicant：	Qun Chen	Study leader：	Qingsheng Xu
申请注册联系人电话： Applicant telephone：	+86 571 8723 6821	研究负责人电话： Study leader's telephone：	+86 571 8723 6821
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：	chenqunmagician@sina.com	研究负责人电子邮件： Study leader's E-mail：	xuqingsheng79@zju.edu.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：	浙江省杭州市上城区庆春路79号	研究负责人通讯地址：	浙江省杭州市上城区庆春路79号
Applicant address：	No. 79, Qingchun Road, Shangcheng District, Hangzhou City, Zhejiang Province	Study leader's address：	No. 79, Qingchun Road, Shangcheng District, Hangzhou City, Zhejiang 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：	浙江大学医学院附属第一医院
Applicant's institution：	The First Affiliated Hospital, Zhejiang University School of Medicine
研究负责人所在单位：	浙江大学医学院附属第一医院
Affiliation of the Leader：	The First Affiliated Hospital, Zhejiang University School of Medicine

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：	浙大一院伦审2025研第112号-会	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：	浙江大学医学院附属第一医院IIT伦理审查委员会
Name of the ethic committee：	Clinical Research Ethics Committee of the First Affiliated Hospital, College of Medicine, Zhejiang University
伦理委员会批准日期： Date of approved by ethic committee：	2025-07-10 00:00:00
伦理委员会联系人：	吕朵
Contact Name of the ethic committee：	Duo Lv
伦理委员会联系地址：	浙江省杭州市上城区庆春路79号
Contact Address of the ethic committee：	No. 79, Qingchun Road, Shangcheng District, Hangzhou City, Zhejiang Province
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 571 8723 3418	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：

浙江大学医学院附属第一医院

Primary sponsor：

The First Affiliated Hospital, Zhejiang University School of Medicine

研究实施负责（组长）单位地址：

浙江省杭州市上城区庆春路79号

Primary sponsor's address：

No. 79, Qingchun Road, Shangcheng District, Hangzhou City, Zhejiang 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)：	浙江	市(区县)：	杭州
Country：	China	Province：	Zhejiang	City：	Hangzhou
单位(医院)：	浙江大学医学院附属第一医院	具体地址：	浙江省杭州市上城区庆春路79号
Institution hospital：	The First Affiliated Hospital, Zhejiang University School of Medicine	Address：	No. 79, Qingchun Road, Shangcheng District, Hangzhou City, Zhejiang Province

经费或物资来源：

无

Source(s) of funding：

None

研究疾病：

肺腺癌难治性柔脑膜转移

Target disease：

Refractory leptomeningeal metastases from lung adenocarcinoma

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：

随机平行对照

Study design：

Parallel

研究目的：

评估培美曲塞鞘内化疗同步放疗伴后续长周期鞘内化疗对于肺腺癌伴难治性柔脑膜转移受试者的有效性、安全性以及脑脊液肿瘤标志物（CEA、CA199、CA125）对疗效评估的价值。

Objectives of Study：

To evaluate the efficacy and safety of concurrent radiotherapy and intrathecal pemetrexed followed by long-term intrathecal maintenance chemotherapy in patients with refractory leptomeningeal metastases from lung adenocarcinoma, as well as the value of cerebrospinal fluid tumor markers (CEA, CA199, and CA125) in assessing treatment response.

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. Be over 18 years old (including 18 years old) and under 75 years old (including 75 years old).
2.Eastern Cooperative Oncology Group (ECOG) performance status score 0-2, KPS > =60, the expected survival time is not less than 12 weeks.
3. Patients diagnosed with leptomeningeal metastases (including brain tissue metastases) from lung adenocarcinoma according to the 2023 ELANO-ESMO guideline criteria.
4. Failure of first-line treatment for leptomeningeal metastases: (1) LM was diagnosed during TKI treatment in patients with ROS1 fusion gene, NTRK fusion gene, KRAS G12C mutation, MET amplification or skipping mutation in exon 14, RET fusion gene, HER-2 mutation or BRAF V600 mutation; Or if LM was diagnosed and LM progressed during TKI treatment; (2) Leptomeningeal metastases in patients with T790M mutation treated with TKIs or ALK fusion gene positive NSCLS who failed to respond to third-generation EGFR-TKI inhibitors or second/third generation ALK inhibitors; Patients with leptomeningeal metastasis of NSCLS without T790M mutation but disease progression after the first/second/third generation EGFR-TKI inhibitor treatment; (3) Leptomeningeal metastasis from NSCLS with negative driver genes after failure of first-line treatment.
5. Adequate organ function (neutrophil count > =1500/mm^3, platelet count > =70,000/ mm^3, hemoglobin concentration > =7.0 g/dL, serum total bilirubin concentration < =1.5mg/dL, serum aminotransferase concentration < =2.5 times the limit of normal value; Serum creatinine < = 1.5 times the upper limit of normal, SpO2 > = 90% in room air, proteinuria < =1+).
6. The patient's brain parenchymal metastases and peripheral tumor lesions were stable.
7. Understand and sign the informed consent.

排除标准：

1.HIV阳性患者。 2.培美曲塞系统化疗以及放疗过敏史。 3.严重感染或严重合并症，如出血性消化性溃疡，肠梗阻，心力衰竭，肾衰竭或控制不佳的糖尿病。 4.不能遵守试验要求者。 5.妊娠（经血清或尿β人绒毛膜促性腺激素[β-HCG]证实）或哺乳期。

Exclusion criteria：

1. Hiv-positive patients. 2. History of allergy to pemetrexed system chemotherapy and radiotherapy. 3. Severe infection or serious complications such as hemorrhagic peptic ulcer, intestinal obstruction, heart failure, renal failure or poorly controlled diabetes. 4. Failure to comply with the requirements of the test. 5. Pregnancy (confirmed by serum or urinary β-human chorionic gonadotropin [β-HCG]) or lactation

研究实施时间：

Study execute time：

从 From 2025-09-15 00:00:00至 To 2029-08-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2025-10-01 00:00:00 至 To 2027-09-30 00:00:00

干预措施：

Interventions：

组别：	同步放化疗组	样本量：	37
Group：	Concurrent chemoradiotherapy group	Sample size：	37
干预措施：	第一阶段（诱导阶段）：15mg 培美曲塞鞘内化疗同步放化疗阶段：培美曲塞鞘内化疗(30mg Q3W，为一周期），共6周期+同步放疗维持阶段：培美曲塞鞘内化疗（30mg Q3W），直至疾病进展或治疗不耐受。 #所有符合入组条件的受试者接受培美曲塞鞘内（Ommaya储液囊或腰椎穿刺）注射：培美曲塞：规格200mg/支；每次鞘内注射培美曲塞时，鞘内同时注射5mg地塞米松。每日口服叶酸片0.4mg，每次鞘内注射前一天肌肉注射维生素B12 1mg。在选择放疗技术时应考虑脑转移进展或中枢神经系统外疾病进展 (如果脑转移进展适合立体定向放射治疗（SRT，stereotactic radiotherapy），应优先考虑SRT;如果脑转移进展不适合SRT，或者中枢神经系统外疾病进展没有有效的全身治疗选择，可以考虑全脑放疗、脑脊髓放疗或者脊髓放疗)。放疗技术：采用容积旋转调强放疗（Volume Modulated Arc Therapy，VMAT）技术或螺旋断层放射治疗（Tomotherapy，TOMO）技术。放疗剂量如下： SRS：18-24Gy，ONCE 全脑放疗：DT 30Gy/10f，3Gy/F，5F/W 脊髓放疗：结节状类型（脊髓MRI显示明显病灶且症状明显）DT 30-40Gy/15-20F，1.8-2Gy/F，5F/W；弥漫性类型（仅脑脊液阳性，增强MRI阴性）：DT 24-30Gy/12-17F，1.8-2Gy/F，5F/W 全脑全脊髓：DT 30.6Gy/17F,1.8Gy/F，5F/W,局部病灶可加量至40Gy。系统性治疗：入组期间患者系统性治疗方案（例如TKI，化疗）不变。	干预措施代码：
Intervention：	Phase I (induction phase) : 15mg pemetrexed intrathecal chemotherapy Concurrent chemoradiotherapy stage: pemetrexed intrathecal chemotherapy (30mg Q3W, one cycle), a total of 6 cycles + concurrent radiotherapy Maintenance phase: pemetrexed intrathecal chemotherapy (30mg Q3W) until disease progression or treatment intolerance. # All eligible subjects received pemetrexed intrathecal (Ommaya reservoir or lumbar puncture) injection: Pemetrexed: specification 200mg/ plug; At each intrathecal injection of pemetrexed, 5mg of dexamethasone was administered intrathecally. Folic acid tablets 0.4mg were taken orally daily, and vitamin B12 1mg was injected intramusitoneally the day before each intrathecal injection. The progression of brain metastasis or disease outside the central nervous system should be considered when selecting radiotherapy techniques. If the progression of brain metastasis is suitable for stereotactic radiotherapy, stereotactic radiotherapy should be given priority. Whole brain, spinal cord, or spinal cord radiotherapy may be considered if brain metastases are not amenable to SRT or if there are no effective systemic treatment options for disease progression outside the central nervous system.) The patients were treated with Volume Modulated Arc Therapy (VMAT) or Tomotherapy (TOMO). Radiation doses were as follows: SRS: 18-24Gy, ONCE Whole brain radiotherapy: DT 30Gy/10f, 3Gy/F, 5F/W Spinal cord radiotherapy: nodular type (spinal cord MRI showed obvious lesions and obvious symptoms) DT 30-40Gy/15-20F, 1.8-2Gy/F, 5F/W; Diffuse type (CSF positive only, contrast-enhanced MRI negative) : DT 24-30Gy/12-17F, 1.8-2Gy/F, 5F/W Whole brain and whole spinal cord: DT 30.6Gy/17F,1.8Gy/F, 5F/W, local lesions can be boosted to 40Gy. Systemic therapy: Systemic therapy (e.g., TKI, chemotherapy) remained unchanged during enrollment.	Intervention code：

组别：	对照组	样本量：	38
Group：	Control group	Sample size：	38
干预措施：	第一阶段（诱导阶段）：15mg 培美曲塞鞘内化疗，维持一周化疗阶段：培美曲塞鞘内化疗#（30mg Q3W），直至疾病进展或治疗不耐受。所有符合入组条件的受试者接受培美曲塞鞘内（Ommaya储液囊或腰椎穿刺）注射：培美曲塞：规格200mg/支；每次鞘内注射培美曲塞时，鞘内同时注射5mg地塞米松。每日口服叶酸片0.4mg，每次鞘内注射前一天肌肉注射维生素B12 1mg。	干预措施代码：
Intervention：	Phase I (induction phase) : 15mg pemetrexed intrathecal chemotherapy was maintained for one week Chemotherapy phase: pemetrexed intrathecal chemotherapy # (30mg Q3W) until disease progression or treatment intolerance. All subjects who met the inclusion criteria received pemetrexed intrathecal (Ommaya reservoir or lumbar puncture) injection: pemetrexed: specification 200mg/ plug; At each intrathecal injection of pemetrexed, 5mg of dexamethasone was administered intrathecally. Folic acid tablets 0.4mg were taken orally daily, and vitamin B12 1mg was injected intramusitoneally the day before each intrathecal injection.	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	浙江	市(区县)：	杭州
Country：	China	Province：	Zhejiang	City：	Hangzhou
单位(医院)：	浙江大学医学院附属第一医院	单位级别：	三甲
Institution hospital：	The First Affiliated Hospital, Zhejiang University School of Medicine	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	评估培美曲塞鞘内化疗同步放疗伴后续长周期鞘内化疗于肺腺癌伴难治性柔脑膜转移受试者的颅内无进展生存时间（iPFS）。	指标类型：	主要指标
Outcome：	To evaluate the intracranial progression-free survival (iPFS) of intrathecal pemetrexed chemotherapy combined with concurrent radiotherapy followed by long-term intrathecal maintenance chemotherapy in patients with refractory leptomeningeal metastases from lung adenocarcinoma.	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	总生存时间	指标类型：	次要指标
Outcome：	Overall survival time	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	颅内疾病控制率	指标类型：	次要指标
Outcome：	Intracranial disease control rate	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	脑脊液肿瘤标志物（CEA、CA199、CA125）对疗效评估的价值	指标类型：	次要指标
Outcome：	The value of cerebrospinal fluid tumor markers (CEA, CA199, and CA125) in the assessment of therapeutic efficacy	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：	脑脊液	组织：
Sample Name：	Cerebrospinal fluid	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	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）：

使用随机数字表进行随机

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

Use a random number table for randomization

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：	无
Blinding：	None
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
数据与安全监察委员会： Data and Safety Monitoring Committee：	有/Yes
注册人： Name of Registration：	2025-09-29 10:24:45