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

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.

Inclusion Criteria:

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Participants can be enrolled in this study only if they meet all of the following inclusion criteria:

1. Age ≥ 18 years old;
2. Diagnosed with lung cancer by pathological biopsy or cytology;
3. Diagnosed with meningeal metastasis by detecting tumor cells in cerebrospinal fluid cytology;
4. Patients with advanced lung cancer and meningeal metastasis who have failed standard treatment;
5. ECOG PS 0 - 3.

Exclusion Criteria:

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The following conditions will disqualify a patient from participating in this study:

1. Concurrent central nervous system infectious diseases;
2. ECOG PS ≥ 4;
3. Patients currently participating in other interventional studies;
4. History of or current severe immunodeficiency diseases;
5. Any other conditions that, in the judgment of the researcher, make the patient unfit to participate in this study.