OncoMatch/Clinical Trials/NCT05805631
Intrathecal Pemetrexed for Leptomeningeal Metastasis in EGFR-Mutant NSCLC
Is NCT05805631 recruiting? Yes, currently enrolling (May 2026). This Phase 2 trial studies Pemetrexed for carcinoma, non-small-cell lung.
Treatment: Pemetrexed — 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.
Check if I qualifyExtracted eligibility criteria
Cancer type
Non-Small Cell Lung Carcinoma
Biomarker criteria
Required: EGFR exon 19 deletion
Required: EGFR g719x
Required: EGFR l858r
Required: EGFR l861q
Required: EGFR s768i
Required: EGFR t790m
Disease stage
Metastatic disease required
Performance status
ECOG 0–3(Limited self-care)
Prior therapy
Must have received: EGFR tyrosine kinase inhibitor (osimertinib)
Intracranial disease progression after osimertinib use, proved by contrast-enhanced MRI
Cannot have received: systemic cytotoxic chemotherapy
Exception: within 2 weeks of the first dose of study medication
Systemic cytotoxic chemotherapy or major surgery within 2 weeks of the first dose of study medication
Cannot have received: intrathecal chemotherapy
Exception: within 2 weeks before the start of IP
Has received intrathecal chemotherapy within 2 weeks before the start of IP
Cannot have received: radiation therapy (whole-brain radiotherapy)
Exception: within 2 weeks before the start of IP
Has received whole-brain radiotherapy (WBRT) within 2 weeks before the start of IP
Lab requirements
Blood counts
Hemoglobin ≥9gm/dL, ANC ≥1500/mm3, platelets ≥100,000/mm3
Kidney function
Creatinine clearance (Ccr) ≥45 mL/min.
Liver function
Serum total bilirubin ≤1.5 x upper limit of normal (ULN), ALT (SGPT) and AST (SGOT) ≤3 x ULN.
Normal bone marrow and organ function as defined below: * Marrow: Hemoglobin ≥9gm/dL, ANC ≥1500/mm3 platelets ≥100,000/mm3 * Hepatic: Serum total bilirubin ≤1.5 x upper limit of normal (ULN), ALT (SGPT) and AST (SGOT) ≤3 x ULN. * Renal: Creatinine clearance (Ccr) ≥45 mL/min.
Structured fields extracted by AI. May contain errors — verify against the official protocol.
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