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NCT Number: NCT06861218

Cerebrospinal Fluid Cytology-guided Intrathecal Chemo-holiday Therapy for EGFR-positive NSCLC Leptomeningeal Metastases

With the rapid development of targeted drugs, the treatment of patients with leptomeningeal metastasis has become a very difficult problem in clinical work. High-dose targeted drugs and intrathecal chemotherapy are important treatment methods for meningeal metastasis. However, it is vital to note that safety is also of concern in previous studies of intrathecal chemotherapy. In this study, we aim to evaluate the safety and effectiveness of patient using chemo-holiday therapy based on the cerebrospinal fluid cytology, combined with double-dose EGFR-targeted drug in patients with leptomeningeal metastases from EGFR-positive NSCLC.

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Key information

Conditions

Leptomeningeal Metastases 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

Phase 2

Primary location

About this study

This is a single arm phase II clinical trial. The objective of the study is patients with leptomeningeal metastases from non-small cell lung cancer after EGFR TKIs treatment. The pemetrexed is administrated by intrathecal injection with a dose of 50mg, once per week for 4 weeks, followed by every four weeks thereafter. The cerebrospinal fluid(CSF) samples are collected every 4 weeks and the cytology examination will be performed. If CSF cytology was negative, CSF cytology was tested again 1 week later. Two negative tests were considered as negative CSF cytology. If the cytology of cerebrospinal fluid was negative after 4 consecutive intrathecal injections, the intrathecal injection should be stopped. If positive, continue to give a intrathecal injection every 4 weeks until CSF cytology is negative. If CSF cytological positivity or worsening of neurological symptoms occurs again during discontinuation, or if new symptoms appear, the intrathecal injection should be resumed every 4 weeks. in the meantime, double dose of vometinib (160mg) is given.

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 EGFR mutations.
  • Cytologically confirmed diagnosis of leptomeningeal metastasis.
  • Normal organ function.
  • 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

The pemetrexed is administrated by intrathecal injection with a dose of 50mg, once per week for 4 weeks, followed by every four weeks thereafter. The cerebrospinal fluid(CSF) samples are collected every 4 weeks and the cytology examination will be performed. If CSF cytology was negative, CSF cytology was tested again 1 week later. Two negative tests were considered as negative CSF cytology. If the cytology of cerebrospinal fluid was negative after 4 consecutive intrathecal injections, the intrathecal injection should be stopped. If positive, continue to give a intrathecal injection every 4 weeks until CSF cytology is negative. If CSF cytological positivity or worsening of neurological symptoms occurs again during discontinuation, or if new symptoms appear, the intrathecal injection should be resumed every 4 weeks.

vometinib

Drug

double dose of vometinib (160mg)

Primary outcomes

  1. Overall survival

    Time frame: From the enrollment of this study until date of death from any cause, up to a maximum of approximately 2 years

    Overall survival is the time from the date of enrollment of this study to death due to any cause.

Secondary outcomes

  1. Impact on quality of life

    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.

    Impact on quality of life using QLQ-C30 (V3.0)

  2. 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.

  3. leptomeningeal metastases related progression-free survival

    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.

    The neurological progression was determined based on the RANO proposal evaluation criteria which have been established and published on Neuro Oncol.

  4. CSF cytological clearance

    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 cerebrospinal fluid samples are collected every 4 weeks and the cytology examination will be performed.

  5. 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 according to Common Toxicity Criteria Adverse Event (CTCAE), version 5.0.

Study contacts

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

Department of Thoracic Oncology, Zhejiang Cancer Hospital

CONTACT

[email protected]

+86-0571-88122092

Sponsors and collaborators

Lead sponsor

Zhejiang Cancer Hospital

Other

Registry information

Official study title

Cerebrospinal Fluid Cytology-guided Intrathecal Chemo-holiday Therapy for EGFR-positive NSCLC Meningeal Metastases: a One-arm, Phase II Clinical Study

Important dates

Study start
2025
Primary completion
2028
Study completion
2028
First posted
Mar 6, 2025
Registry last updated
Mar 6, 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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