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

NCT06861218 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: ZhejiangCH-IRB-2024-1191(IIT)
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Leptomeningeal Metastases

Keywords

Leptomeningeal Metastases; EGFR; Pemetrexed; intrathecal injection; vometinib

Outcome Measures

Primary Outcomes (1)

• Overall survival

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

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

Secondary Outcomes (5)

• Impact on quality of life

  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.

• Clinical response rate

  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.

• leptomeningeal metastases related progression-free survival

  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.

• CSF cytological clearance

  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.

• Adverse events

  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.

Study Arms (1)

intrathecal injection of pemetrexed and double dose of vometinib

EXPERIMENTAL

Drug: pemetrexed; Drug: vometinib

Interventions

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.

intrathecal injection of pemetrexed and double dose of vometinib

vometinib DRUG

double dose of vometinib (160mg)

intrathecal injection of pemetrexed and double dose of vometinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Zhejiang Cancer Hospital: lead

Study Sites (1)

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Location

MeSH Terms

Conditions

Meningeal Carcinomatosis

Interventions

Pemetrexed

Condition Hierarchy (Ancestors)

Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Central Study Contacts

Department of Thoracic Oncology, Zhejiang Cancer Hospital

CONTACT

+86-0571-88122092; yusz@zjcc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof

Study Record Dates

• First Submitted: December 30, 2024
• First Posted: March 6, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: March 6, 2025

Record last verified: 2025-03

Locations

CN (1)