Exploration of the Application of Methotrexate-loaded Drug Vesicles in Intrathecal Injection for Meningeal Metastasis of Lung Cancer
24. april 2026 oppdatert 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.
Studieoversikt
Status
Rekruttering
Intervensjon / Behandling
Studietype
Intervensjonell
Registrering (Antatt)
14
Fase
- Fase 2
- Fase 1
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Henan
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Zhengzhou, Henan, Kina, 450000
- Rekruttering
- Wang Qiming
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Ta kontakt med:
- Wang Qiming, PhD
- Telefonnummer: 037165588421
- E-post: qimingwang1006@126.com
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-
Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
- Eldre voksen
Tar imot friske frivillige
Nei
Beskrivelse
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
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Phase I: Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D)
Tidsramme: 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
|
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Phase II:Objective Response Rate(ORR)
Tidsramme: 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).
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Expected for 15 months
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Safety and Tolerability
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Generelle publikasjoner
- 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.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart (Faktiske)
8. september 2025
Primær fullføring (Antatt)
31. desember 2026
Studiet fullført (Antatt)
31. desember 2027
Datoer for studieregistrering
Først innsendt
24. april 2026
Først innsendt som oppfylte QC-kriteriene
24. april 2026
Først lagt ut (Faktiske)
30. april 2026
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
30. april 2026
Siste oppdatering sendt inn som oppfylte QC-kriteriene
24. april 2026
Sist bekreftet
1. april 2026
Mer informasjon
Begreper knyttet til denne studien
Andre studie-ID-numre
- 2024-386
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
NEI
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Nei
Studerer et amerikansk FDA-regulert enhetsprodukt
Nei
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .