Actively Recruiting

Phase 2
Age: 20Years +
All Genders
NCT05805631

Intrathecal Pemetrexed for Leptomeningeal Metastasis in EGFR-Mutant NSCLC

Led by Taipei Veterans General Hospital, Taiwan · Updated on 2026-03-24

23

Participants Needed

1

Research Sites

178 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

Leptomeningeal metastasis (LM) is a complication of advanced non-small cell lung cancer (NSCLC). The incidence of LM in NSCLC patients is around 3-5 %, reaching 9.4 % of those with an epidermal growth factor receptor (EGFR) mutation. Generally, the efficacy of systemic treatment for LM is limited due to the blood-brain barrier. Osimertinib has a high central nervous system penetration rate, making it the preferred first-line treatment for EGFR-mutant NSCLC. Previous studies indicated that osimertinib had shown promising efficacy in pretreated patients harboring EGFR mutations and LM. However, intracranial disease progression eventually develops, and the prognosis of patients with LM progression after osimertinib is poor. Recently, intrathecal chemotherapy with pemetrexed (IP) was reported to be an alternative treatment in patients with NSCLC and LM. The results from a phase I/II trial examining the efficacy and safety of IP in patients with EGFR-mutant NSCLC after the failure of previous TKI, and 83% of study enrollees received osimertinib before IP. The clinical response rate was 84.6%, and the median overall survival was 9.0 months. Despite initial promising efficacy, further trials are needed to verify these results. Therefore, the investigators plan to conduct a prospective study to examine the safety and effectiveness of IP combined with EGFR-TKI for patients with EGFR mutant NSCLC after osimertinib failure.

CONDITIONS

Official Title

Intrathecal Pemetrexed for Leptomeningeal Metastasis in EGFR-Mutant NSCLC

Who Can Participate

Age: 20Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • At least 20 years of age.
  • Diagnosis of metastatic non-squamous NSCLC with known EGFR activating mutation (exon19 deletion, T790M, L858R, G719X, L861Q, or S768I).
  • Probable or confirmed leptomeningeal metastasis by EANO-ESMO guideline.
  • Intracranial disease progression after osimertinib use, confirmed by contrast-enhanced MRI.
  • Stable disease outside the central nervous system.
  • Eastern Cooperative Oncology Group (ECOG) performance status between 0 and 3.
  • Minimum life expectancy of 12 weeks.
  • Normal bone marrow function (Hemoglobin ≥9 gm/dL, ANC ≥1500/mm3, platelets ≥100,000/mm3).
  • Normal liver function (total bilirubin ≤1.5 times upper limit of normal, ALT and AST ≤3 times upper limit of normal).
  • Normal kidney function (creatinine clearance ≥45 mL/min).
  • For women of childbearing potential, agreement to use highly effective contraception during the study and for 5 months after last dose of intrathecal pemetrexed.
  • Ability to understand and sign informed consent.
  • Willingness to provide cerebrospinal fluid and plasma samples for ctDNA analysis.
Not Eligible

You will not qualify if you...

  • Uncontrolled disease outside the central nervous system requiring treatments other than EGFR-TKI.
  • Uncontrolled tumor-related pain.
  • Uncontrolled or symptomatic high calcium levels (hypercalcemia).
  • Other malignancies within 5 years except those with negligible risk or curatively treated.
  • Use of systemic steroids over 20 mg prednisolone per day or other immunosuppressive medications.
  • Receipt of live-virus vaccination within 30 days before starting treatment.
  • Systemic chemotherapy or major surgery within 2 weeks prior to first dose.
  • Active infection requiring treatment.
  • History of HIV infection.
  • Hepatitis B carrier without effective antiviral therapy or viral load above 100 IU/mL.
  • Active Hepatitis C infection.
  • Intrathecal chemotherapy within 2 weeks before starting intrathecal pemetrexed.
  • Whole-brain radiotherapy within 2 weeks before starting intrathecal pemetrexed.
  • Uncontrolled epilepsy.
  • Allergy to intravenous pemetrexed.
  • Severe blood clotting problems (INR > 2).
  • Severe hydrocephalus requiring treatment other than intrathecal pemetrexed.
  • Large intracranial lesions requiring other treatments besides intrathecal pemetrexed.

AI-Screening

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Trial Site Locations

Total: 1 location

1

Department of Chest Medicine, Taipei Veterans General Hospital

Taipei, Taiwan, Taiwan, 11217

Actively Recruiting

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Research Team

C

Chi-Lu Chiang, MD

CONTACT

Y

Yung-Hung Luo, MD, PhD

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

1

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