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NCT Number: NCT06296745

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

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.

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Key information

Conditions

Leptomeningeal Metastasis Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Central Nervous System Neoplasms Lung Diseases Lung Neoplasms Meningeal Carcinomatosis Meningeal Neoplasms Neoplasms Neoplasms by Site Nervous System Diseases Nervous System Neoplasms Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

The Affiliated Huizhou Hospital, Guangzhou Medical University

Huizhou, Guangdong, 516000, China

Location status: Recruiting

Location contact

Guozi Yang

CONTACT

[email protected]

+8615804302755

About this study

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.

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.
  • Progression after previous double doses of third-generation TKIs such as Osimertinib.
  • 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

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 treatment 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.

  2. Neurological progression-free survival (NPFS)

    Time frame: From date of treatment until the date of first documented neurological progression or date of death from any cause, whichever came first, assessed up to 6 months.

    NPFS was defined as time from the start of treatment until neurological progression or death. The neurological progression was determined based on the RANO proposal evaluation criteria which have been established and published on Neuro Oncol.

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 treatment 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

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

Important dates

Study start
2025
Primary completion
2026
Study completion
2027
First posted
Mar 6, 2024
Registry last updated
Jan 30, 2026

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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