NCT06304441

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

Recruiting now NA Last updated 24 September 2025

What this trial tests

NA trial testing Osimertinib in Leptomeningeal Metastasis in 100 participants. Currently enrolling.

Timeline

18 April 2024

Primary endpoint
20 June 2026

1 September 2026

Quick facts

Lead sponsor	Guangzhou Medical University
Phase	NA
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	100
Start date	18 April 2024
Primary completion	20 June 2026
Estimated completion	1 September 2026
Sites	1 location across China

Drugs / interventions tested

• Osimertinib (osimertinib) — full drug profile →
• Pemetrexed — full drug profile →

Conditions studied

• Leptomeningeal Metastasis — all drugs for Leptomeningeal Metastasis →

Sponsor

Guangzhou Medical University

Who can join

Adults 18 to 75, any sex, with Leptomeningeal Metastasis. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Clinical response rate
  Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months.
  The response assessment in neuro-oncology criteria (RANO) proposal for response criteria of leptomeningeal metastasis was used to assess the clinical response in this study.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Advancing leptomeningeal metastases treatment in <i>EGFR</i>-mutated non-small cell lung cancer: lessons from the BLOSSOM trial.
   Bortolot M, Huijs JWJ, Brandsma D, Compter A, et al · · 2025 · cited 1× · PMID 39958217 · DOI 10.21037/tlcr-24-1006
2. PD-L1 expression in cerebrospinal fluid for leptomeningeal metastasis from solid tumors: preliminary assessment of clinical implications.
   Pan Z, Lei H, Huang Y, Liu M, et al · · 2025 · PMID 41089694 · DOI 10.3389/fimmu.2025.1681280