Leptomeningeal Metastasis From Lung Cancer
Conditions
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.
Interventions
BIOLOGICALMethotrexate-loaded vesicles
Intrathecal injection of methotrexate-loaded vesicles
Sponsors
Henan Cancer Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
\- 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
\- 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase I: Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D) | Expected for 15 months | Phase I: To determine the MTD and RP2D using an accelerated titration plus 3+3 dose-escalation design. |
| Phase II:Objective Response Rate(ORR) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability | From first dose up to 30 days after last dose (or study completion) | 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) | From first dose up to approximately 15 months | 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) | From first dose up to approximately 27 months. | Time from first dose of study drug to death from any cause. |
Countries
China
Outcome results
None listed