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.
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;
Concurrent central nervous system infectious diseases;
ECOG PS ≥ 4;
Patients currently participating in other interventional studies;
History of or current severe immunodeficiency diseases;
Single group
Methotrexate-loaded vesicles
Biological/VaccineIntrathecal injection of methotrexate-loaded vesicles
Phase I: Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D)
Phase I: To determine the MTD and RP2D using an accelerated titration plus 3+3 dose-escalation design.
Phase II:Objective Response Rate(ORR)
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).
Safety and Tolerability
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.
Progression-Free Survival (PFS)
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.
Overall Survival (OS)
Time from first dose of study drug to death from any cause.
Click on the lead sponsor to view all of their trials.
