NCT06296745

Intrathecal Pemetrexed for Leptomeningeal Metastasis From Lung Adenocarcinoma That Progressed After Osimertinib.

An Open-label, Single-arm, Phase II Trial of Intrathecal Pemetrexed for Leptomeningeal Metastasis From Lung Adenocarcinoma That Progressed After a Double Dose of Third-generation TKIs, Including Osimertinib

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 36 (estimated)
• Sponsor: Guangzhou Medical University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

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 treating non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations. 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, the choice of treatment after resistance to targeted therapy is a hot topic in clinical practice, with 78% of patients in the study above who responded to double-dose osimertinib still showing progression at the time of follow-up. The purpose of this study was to observe the safety and efficacy of intrathecal pemetrexed for leptomeningeal metastasis from lung adenocarcinoma that progressed after a double dose of a third-generation TKI such as osimertinib.

Detailed description

This study is a single arm, open and phase II clinical trial. Consecutive patients with leptomeningeal metastases from lung adenocarcinoma that progressed after a double dose of a third-generation TKI such as osimertinib are enrolled in this study. Concomitant regimen consisted of intrathecal chemotherapy (via lumbar puncture, pemetrexed 15 mg, plus dexamethasone 5 mg, twice a week for 2 weeks as an induction phase, followed by once a week for 4 weeks as a consolidation phase. Thereafter, the maintenance phase is once a month). The RANO proposal for response criteria of leptomeningeal metastasis was used to assess the clinical response in this study.

Conditions

• Leptomeningeal Metastasis

Interventions

Type	Name	Description
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: 2025-09-01
• Primary completion: 2026-01-20
• Completion: 2027-03-20
• First posted: 2024-03-06
• Last updated: 2026-01-30

Locations

1 site across 1 country: China