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

NCT07559097 | Recruiting Phase 1

• 1 other identifier: 2024-386
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Leptomeningeal Metastasis From Lung Cancer

Outcome Measures

Primary Outcomes (2)

• 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.

  Expected for 15 months

• 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).

  Expected for 15 months

Secondary Outcomes (3)

• Safety and Tolerability

  From first dose up to 30 days after last dose (or study completion)

• Progression-Free Survival (PFS)

  From first dose up to approximately 15 months

• Overall Survival (OS)

  From first dose up to approximately 27 months.

Interventions

Methotrexate-loaded vesicles BIOLOGICAL

Intrathecal injection of methotrexate-loaded vesicles

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Henan Cancer Hospital: lead

Study Sites (1)

Wang Qiming

Zhengzhou, Henan, 450000, China

RECRUITING

Related Publications (18)

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Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 24, 2026
• First Posted: April 30, 2026
• Study Start: September 8, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)