Exploration of the Application of Methotrexate-loaded Drug Vesicles in Intrathecal Injection for Meningeal Metastasis of Lung Cancer
24 april 2026 uppdaterad av: 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.
Studieöversikt
Status
Rekrytering
Betingelser
Intervention / Behandling
Studietyp
Interventionell
Inskrivning (Beräknad)
14
Fas
- Fas 2
- Fas 1
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
-
-
Henan
-
Zhengzhou, Henan, Kina, 450000
- Rekrytering
- Wang Qiming
-
Kontakt:
- Wang Qiming, PhD
- Telefonnummer: 037165588421
- E-post: qimingwang1006@126.com
-
-
Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
- Vuxen
- Äldre vuxen
Tar emot friska volontärer
Nej
Beskrivning
Inclusion Criteria:
-
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.
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: N/A
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Phase I: Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D)
Tidsram: Expected for 15 months
|
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
|
|
Phase II:Objective Response Rate(ORR)
Tidsram: Expected for 15 months
|
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).
|
Expected for 15 months
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Safety and Tolerability
Tidsram: From first dose up to 30 days after last dose (or study completion)
|
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)
Tidsram: 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)
Tidsram: From first dose up to approximately 27 months.
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Time from first dose of study drug to death from any cause.
|
From first dose up to approximately 27 months.
|
Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Publikationer och användbara länkar
Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.
Allmänna publikationer
- 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.
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart (Faktisk)
8 september 2025
Primärt slutförande (Beräknad)
31 december 2026
Avslutad studie (Beräknad)
31 december 2027
Studieregistreringsdatum
Först inskickad
24 april 2026
Först inskickad som uppfyllde QC-kriterierna
24 april 2026
Första postat (Faktisk)
30 april 2026
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
30 april 2026
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
24 april 2026
Senast verifierad
1 april 2026
Mer information
Termer relaterade till denna studie
Andra studie-ID-nummer
- 2024-386
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