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

Phase 2

Not yet recruiting

• Conditions: Leptomeningeal Metastases
• Interventions: Drug: pemetrexed; Drug: vometinib

• Registration Number: NCT06861218
• Lead Sponsor: Zhejiang Cancer Hospital

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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2024-12-30
• Status Verified: 2025-03
• Study First Submitted QC: 2025-03-05
• Last Update Submitted: 2025-03-05
• Study First Posted: 2025-03-06
• Last Update Posted: 2025-03-06
• Study Start: 2025-04
• Primary Completion: 2028-05
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

1. Male or female aged between 18 and 75 years.
2. Histologically or cytologically confirmed diagnosis of NSCLC with EGFR mutations.
3. Cytologically confirmed diagnosis of leptomeningeal metastasis.
4. Normal organ function.
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: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
intrathecal injection of pemetrexed and double dose of vometinib	pemetrexed	-
intrathecal injection of pemetrexed and double dose of vometinib	vometinib	-

Primary Outcome Measures

Name	Time	Method
Overall survival	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 Outcome Measures

Name	Time	Method
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.	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.
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.	Impact on quality of life using QLQ-C30 (V3.0)
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.	The neurological progression was determined based on the RANO proposal evaluation criteria which have been established and published on Neuro Oncol.
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.	The cerebrospinal fluid samples are collected every 4 weeks and the cytology examination will be performed.
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.	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.

Trial Locations

Locations (1)

Zhejiang Cancer Hospital; 🇨🇳 Hangzhou, Zhejiang, China