Exploration of the Application of Methotrexate-loaded Drug Vesicles in Intrathecal Injection for Meningeal Metastasis of Lung Cancer

Официальное название

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

Обзор

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.

Вмешательства

• Биопрепарат Methotrexate-loaded vesicles
  Intrathecal injection of methotrexate-loaded vesicles

Первичные конечные точки

• Phase I: Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D) [Срок оценки: Expected for 15 months]
• Phase II:Objective Response Rate(ORR) [Срок оценки: Expected for 15 months]

Вторичные конечные точки (3)

• Safety and Tolerability [Срок оценки: From first dose up to 30 days after last dose (or study completion)]
• Progression-Free Survival (PFS) [Срок оценки: From first dose up to approximately 15 months]
• Overall Survival (OS) [Срок оценки: From first dose up to approximately 27 months.]

Критерии участия

Критерии включения

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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.

Критерии исключения

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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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Wang Qiming — Чжэнчжоу

Публикации

• 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. PMID 26841095
• 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. PMID 28110254
• 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. PMID 29304362
• 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. PMID 20627894
• 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. PMID 32375819
• Leibold AT, Monaco GN, Dey M. The role of the immune system in brain metastasis. Curr Neurobiol. 2019 Jul;10(2):33-48. PMID 31097897
• 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. PMID 35048267
• 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. PMID 29165794

Идентификаторы

NCT: NCT07559097 · 2024-386

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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