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

Not Applicable

Recruiting

• Conditions: Leptomeningeal Metastasis
• Interventions: Drug: Osimertinib; Drug: Pemetrexed

• Registration Number: NCT06304441
• Lead Sponsor: Guangzhou Medical University

Brief 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.

Study Timeline

• Status Verified: 2024-03
• Study First Submitted: 2024-03-05
• Study First Submitted QC: 2024-03-05
• Study First Posted: 2024-03-12
• Study Start: 2024-04-18
• Last Update Submitted: 2025-03-18
• Last Update Posted: 2025-03-21
• Primary Completion: 2026-06-20
• Study Completion: 2026-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. Male or female aged between 18 and 75 years.
2. Histologically or cytologically confirmed diagnosis of NSCLC with single activating EGFR mutations (L858R or Exon19Del).
3. Confirmed diagnosis of leptomeningeal metastasis according to ESMO/EANO guidelines.
4. Normal liver and kidney function; WBC≥4000/mm3, Plt≥100000/mm3.
5. No history of severe nervous system disease.
6. No severe dyscrasia.

Exclusion Criteria

1. Any evidence of nervous system failure, including severe encephalopathy, grade 3 or 4 leukoencephalopathy on imaging, and Glasgow Coma Score less than 11.
2. Any evidence of extensive and lethal progressive systemic diseases without effective treatment.
3. Patients with poor compliance or other reasons that were unsuitable for this study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group B	Osimertinib	Third-generation small molecule TKI drugs (e.g. 'osimertinib') alone
Group A	Osimertinib	Intra-pemetrexed plus third-generation small molecule TKI drugs (e.g. 'osimertinib')
Group A	Pemetrexed	Intra-pemetrexed plus third-generation small molecule TKI drugs (e.g. 'osimertinib')

Primary Outcome Measures

Name	Time	Method
Clinical response rate	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.

Secondary Outcome Measures

Name	Time	Method
Overall survival	From the enrollment of this study until date of death from any cause, whichever came first, or the last follow-up (at least 7 months).	Survival time was recorded since the date of patient enrollment. All patients were followed up until death or the end of the study.
Incidence of treatment-related adverse events	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 incidence of treatment-related adverse events were measured for determining tolerability and safety. Adverse events (AEs) are evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE, version 4.03).; Events of grade 3-5 are defined as moderate and severe adverse events.

Trial Locations

Locations (1)

The Third People's Hospital of Huizhou (Huizhou Hospital of Guangzhou Medical University); 🇨🇳 Huizhou, Guangdong, China