NCT06304441

Intra-pemetrexed Plus Third-generation Small Molecule TKI Drugs (e.g. 'Osimertinib') Versus Third-generation Small Molecule TKI Drugs Alone for Leptomeningeal Metastasis From Epidermal Growth Factor Receptor Mutation-Positive Non-Small-cell Lung Cancer

A Clinical Trial of Intra-pemetrexed Plus Third-generation Small Molecule TKI Drugs (e.g. 'Osimertinib') Versus Third-generation Small Molecule TKI Drugs Alone for Leptomeningeal Metastasis From Epidermal Growth Factor Receptor Mutation-Positive Non-Small-cell Lung Cancer

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 100 (estimated)
• Sponsor: Guangzhou Medical University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Intrathecal chemotherapy is one of the mainstay treatment options for leptomeningeal metastases. Pemetrexed is one of the first-line chemotherapeutic agents for non-squamous non-small cell lung cancer (NSCLC). Since 2017, intrathecal pemetrexed has shown good efficacy for patients with leptomeningeal metastases from NSCLC. It has been recommended as the preferred drug for intrathecal chemotherapy by the Chinese Society of Clinical Oncology (CSCO) guidelines. Tyrosine kinase inhibitors (TKIs) play a promising role in the treatment of non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations. Due to its small molecule properties, it can effectively penetrate the central nervous system barrier and deliver an effective antitumor effect. An international multi-center clinical study published in 2019 confirmed that double-dose of osimertinib showed significant improvement in leptomeningeal metastases from NSCLC with EGFR exon 19 deletion or exon 21 L858R/T790M mutation. It makes TKIs the mainstay of treatment for patients with EGFR-mutant NSCLC with leptomeningeal metastases. However, whether third-generation small molecule TKI drugs (e.g. 'osimertinib') combined with intrathecal pemetrexed could benefit patients with LM from EGFR- mutant NSCLC remains undetermined.

Detailed description

The aim of this Study is to compare the effects of intra-pemetrexed Plus third-generation small molecule TKI drugs (e.g. 'osimertinib') versus third-generation small molecule TKI drugs alone in leptomeningeal metastasis from EGFR mutation positive NSCLC.

Conditions

• Leptomeningeal Metastasis

Interventions

Type	Name	Description
DRUG	Osimertinib	Double-dose of TKI (e.g. 'osimertinib' 160 mg) was administered orally once daily until disease progression or unmanageable drug-related toxicity.
DRUG	Pemetrexed	Pemetrexed 15 mg was administered with dexamethasone 5 mg via intraventricular or via lumbar puncture. First, induction intrathecal chemotherapy, twice per week for 2 weeks; then consolidation intrathecal chemotherapy, once per week for 4 weeks; and maintenance intrathecal chemotherapy, once per month until disease progression or unmanageable drug-related toxicity.

Timeline

• Start date: 2024-04-18
• Primary completion: 2026-06-20
• Completion: 2026-09-01
• First posted: 2024-03-12
• Last updated: 2025-09-29

Locations

1 site across 1 country: China