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NCT Number: 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

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.

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Key information

Conditions

Leptomeningeal Metastasis Central Nervous System Neoplasms Meningeal Carcinomatosis Meningeal Neoplasms Neoplasms Neoplasms by Site Nervous System Diseases Nervous System Neoplasms

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

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

Treatment and study plan

Osimertinib

Drug

Double-dose of TKI (e.g. 'osimertinib' 160 mg) was administered orally once daily until disease progression or unmanageable drug-related toxicity.

Pemetrexed

Drug

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.

Primary outcomes

  1. 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.

Secondary outcomes

  1. Overall survival

    Time frame: 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.

  2. Incidence of treatment-related adverse events

    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 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Guozi Yang

CONTACT

[email protected]

+8615804302755

Zhenyu Pan

CONTACT

[email protected]

+8615804302753

Sponsors and collaborators

Lead sponsor

Guangzhou Medical University

Other

Registry information

Official study title

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

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Mar 12, 2024
Registry last updated
Sep 29, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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