Exploration of the Application of Methotrexate-loaded Drug Vesicles in Intrathecal Injection for Meningeal Metastasis of Lung Cancer
2026年4月24日 更新者：Qiming Wang、Henan Cancer Hospital
A Phase I/II, Single-arm, Single-center Clinical Study: Exploration of the Application of Methotrexate-loaded Drug Vesicles in Intrathecal Injection for Meningeal Metastasis of Lung Cancer
This is a phase I/II, single-arm, open-label, single-center clinical trial to evaluate the safety, tolerability, and preliminary efficacy of intrathecal injection of methotrexate-loaded autologous tumor cell-derived microparticles (MTX-MPs) in patients with leptomeningeal metastasis from lung cancer who have failed standard of care.
The study consists of two phases: Phase I employs an accelerated titration combined with a "3+3" dose-escalation design to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D). Phase II further assesses the objective response rate (ORR) at the RP2D. Key secondary endpoints include progression-free survival (PFS), overall survival (OS), and safety profile.
Approximately 10-20 patients with cytologically confirmed leptomeningeal metastasis (age ≥18 years, ECOG PS 0-3) will be enrolled. Participants will receive intrathecal MTX-MPs on days 1, 3, and 5 of the first cycle, followed by once every 3 weeks (Q3W) until disease progression, unacceptable toxicity, or death.
Tumor response will be evaluated using the Response Assessment in Neuro-Oncology (RANO) criteria for leptomeningeal metastasis, and adverse events will be graded according to CTCAE version 5.0. This exploratory study may provide a novel local therapeutic approach for leptomeningeal metastasis from lung cancer.
研究概览
研究类型
介入性
注册 (估计的)
14
阶段
- 阶段2
- 阶段1
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Henan
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Zhengzhou、Henan、中国、450000
- 招聘中
- Wang Qiming
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接触：
- Wang Qiming, PhD
- 电话号码：037165588421
- 邮箱：qimingwang1006@126.com
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
不
描述
Inclusion Criteria:
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Participants can be enrolled in this study only if they meet all of the following inclusion criteria:
- Age ≥ 18 years old;
- Diagnosed with lung cancer by pathological biopsy or cytology;
- Diagnosed with meningeal metastasis by detecting tumor cells in cerebrospinal fluid cytology;
- Patients with advanced lung cancer and meningeal metastasis who have failed standard treatment;
- ECOG PS 0 - 3.
Exclusion Criteria:
-
The following conditions will disqualify a patient from participating in this study:
- Concurrent central nervous system infectious diseases;
- ECOG PS ≥ 4;
- Patients currently participating in other interventional studies;
- History of or current severe immunodeficiency diseases;
- Any other conditions that, in the judgment of the researcher, make the patient unfit to participate in this study.
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Phase I: Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D)
大体时间：Expected for 15 months
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Phase I: To determine the MTD and RP2D using an accelerated titration plus 3+3 dose-escalation design.
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Expected for 15 months
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Phase II:Objective Response Rate(ORR)
大体时间：Expected for 15 months
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Phase II: Objective Response Rate (ORR) per RANO criteria for leptomeningeal metastasis, defined as the proportion of patients achieving complete response (CR) or partial response (PR).
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Expected for 15 months
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Safety and Tolerability
大体时间：From first dose up to 30 days after last dose (or study completion)
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Incidence, severity, and causality of adverse events (AEs) graded by CTCAE v5.0, including acute reactions within 3 days after each intrathecal injection, neurological toxicities, and laboratory abnormalities.
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From first dose up to 30 days after last dose (or study completion)
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Progression-Free Survival (PFS)
大体时间：From first dose up to approximately 15 months
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Time from first dose of study drug to first documented disease progression per RANO criteria for leptomeningeal metastasis, or death from any cause, whichever occurs first.
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From first dose up to approximately 15 months
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Overall Survival (OS)
大体时间：From first dose up to approximately 27 months.
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Time from first dose of study drug to death from any cause.
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From first dose up to approximately 27 months.
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- Yin K, Li YS, Zheng MM, Jiang BY, Li WF, Yang JJ, Tu HY, Zhou Q, Zhong WZ, Yang XN, Chen HJ, Yan HH, Li LL, Wu YL, Zhang XC. A molecular graded prognostic assessment (molGPA) model specific for estimating survival in lung cancer patients with leptomeningeal metastases. Lung Cancer. 2019 May;131:134-138. doi: 10.1016/j.lungcan.2019.03.015. Epub 2019 Mar 18.
- Eichler AF, Kahle KT, Wang DL, Joshi VA, Willers H, Engelman JA, Lynch TJ, Sequist LV. EGFR mutation status and survival after diagnosis of brain metastasis in nonsmall cell lung cancer. Neuro Oncol. 2010 Nov;12(11):1193-9. doi: 10.1093/neuonc/noq076. Epub 2010 Jul 13.
- Hyun JW, Jeong IH, Joung A, Cho HJ, Kim SH, Kim HJ. Leptomeningeal metastasis: Clinical experience of 519 cases. Eur J Cancer. 2016 Mar;56:107-114. doi: 10.1016/j.ejca.2015.12.021. Epub 2016 Feb 1.
- Remon J, Le Rhun E, Besse B. Leptomeningeal carcinomatosis in non-small cell lung cancer patients: A continuing challenge in the personalized treatment era. Cancer Treat Rev. 2017 Feb;53:128-137. doi: 10.1016/j.ctrv.2016.12.006. Epub 2016 Dec 30.
- Cheng H, Perez-Soler R. Leptomeningeal metastases in non-small-cell lung cancer. Lancet Oncol. 2018 Jan;19(1):e43-e55. doi: 10.1016/S1470-2045(17)30689-7.
- Solar P, Zamani A, Kubickova L, Dubovy P, Joukal M. Choroid plexus and the blood-cerebrospinal fluid barrier in disease. Fluids Barriers CNS. 2020 May 6;17(1):35. doi: 10.1186/s12987-020-00196-2.
- Leibold AT, Monaco GN, Dey M. The role of the immune system in brain metastasis. Curr Neurobiol. 2019 Jul;10(2):33-48.
- Lukas RV, Thakkar JP, Cristofanilli M, Chandra S, Sosman JA, Patel JD, Kumthekar P, Stupp R, Lesniak MS. Leptomeningeal metastases: the future is now. J Neurooncol. 2022 Feb;156(3):443-452. doi: 10.1007/s11060-021-03924-2. Epub 2022 Jan 20.
- Wang N, Bertalan MS, Brastianos PK. Leptomeningeal metastasis from systemic cancer: Review and update on management. Cancer. 2018 Jan 1;124(1):21-35. doi: 10.1002/cncr.30911. Epub 2017 Nov 22.
- Wu YL, Zhou L, Lu Y. Intrathecal chemotherapy as a treatment for leptomeningeal metastasis of non-small cell lung cancer: A pooled analysis. Oncol Lett. 2016 Aug;12(2):1301-1314. doi: 10.3892/ol.2016.4783. Epub 2016 Jun 24.
- Gwak HS, Joo J, Kim S, Yoo H, Shin SH, Han JY, Kim HT, Lee JS, Lee SH. Analysis of treatment outcomes of intraventricular chemotherapy in 105 patients for leptomeningeal carcinomatosis from non-small-cell lung cancer. J Thorac Oncol. 2013 May;8(5):599-605. doi: 10.1097/JTO.0b013e318287c943.
- Morris PG, Reiner AS, Szenberg OR, Clarke JL, Panageas KS, Perez HR, Kris MG, Chan TA, DeAngelis LM, Omuro AM. Leptomeningeal metastasis from non-small cell lung cancer: survival and the impact of whole brain radiotherapy. J Thorac Oncol. 2012 Feb;7(2):382-5. doi: 10.1097/JTO.0b013e3182398e4f.
- Liang Q, Bie N, Yong T, Tang K, Shi X, Wei Z, Jia H, Zhang X, Zhao H, Huang W, Gan L, Huang B, Yang X. The softness of tumour-cell-derived microparticles regulates their drug-delivery efficiency. Nat Biomed Eng. 2019 Sep;3(9):729-740. doi: 10.1038/s41551-019-0405-4. Epub 2019 May 20.
- Guo M, Wu F, Hu G, Chen L, Xu J, Xu P, Wang X, Li Y, Liu S, Zhang S, Huang Q, Fan J, Lv Z, Zhou M, Duan L, Liao T, Yang G, Tang K, Liu B, Liao X, Tao X, Jin Y. Autologous tumor cell-derived microparticle-based targeted chemotherapy in lung cancer patients with malignant pleural effusion. Sci Transl Med. 2019 Jan 9;11(474):eaat5690. doi: 10.1126/scitranslmed.aat5690.
- Dong X, Huang Y, Yi T, Hu C, Gao Q, Chen Y, Zhang J, Chen J, Liu L, Meng R, Zhang S, Dai X, Fei S, Jin Y, Yin P, Hu Y, Wu G. Intrapleural infusion of tumor cell-derived microparticles packaging methotrexate or saline combined with pemetrexed-cisplatin chemotherapy for the treatment of malignant pleural effusion in advanced non-squamous non-small cell lung cancer: A double-blind, randomized, placebo-controlled study. Front Immunol. 2022 Oct 5;13:1002938. doi: 10.3389/fimmu.2022.1002938. eCollection 2022.
- Gao Y, Zhang H, Zhou N, Xu P, Wang J, Gao Y, Jin X, Liang X, Lv J, Zhang Y, Tang K, Ma J, Zhang H, Xie J, Yao F, Tong W, Liu Y, Wang X, Huang B. Methotrexate-loaded tumour-cell-derived microvesicles can relieve biliary obstruction in patients with extrahepatic cholangiocarcinoma. Nat Biomed Eng. 2020 Jul;4(7):743-753. doi: 10.1038/s41551-020-0583-0. Epub 2020 Jul 6.
- Tang K, Zhang Y, Zhang H, Xu P, Liu J, Ma J, Lv M, Li D, Katirai F, Shen GX, Zhang G, Feng ZH, Ye D, Huang B. Delivery of chemotherapeutic drugs in tumour cell-derived microparticles. Nat Commun. 2012;3:1282. doi: 10.1038/ncomms2282.
- Ma J, Zhang Y, Tang K, Zhang H, Yin X, Li Y, Xu P, Sun Y, Ma R, Ji T, Chen J, Zhang S, Zhang T, Luo S, Jin Y, Luo X, Li C, Gong H, Long Z, Lu J, Hu Z, Cao X, Wang N, Yang X, Huang B. Reversing drug resistance of soft tumor-repopulating cells by tumor cell-derived chemotherapeutic microparticles. Cell Res. 2016 Jun;26(6):713-27. doi: 10.1038/cr.2016.53. Epub 2016 May 10.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2025年9月8日
初级完成 (估计的)
2026年12月31日
研究完成 (估计的)
2027年12月31日
研究注册日期
首次提交
2026年4月24日
首先提交符合 QC 标准的
2026年4月24日
首次发布 (实际的)
2026年4月30日
研究记录更新
最后更新发布 (实际的)
2026年4月30日
上次提交的符合 QC 标准的更新
2026年4月24日
最后验证
2026年4月1日
更多信息
与本研究相关的术语
其他研究编号
- 2024-386
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药物和器械信息、研究文件
研究美国 FDA 监管的药品
不
研究美国 FDA 监管的设备产品
不
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