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

NCT ID: NCT06861218

Last Updated: 2025-03-06

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-30
• Study Completion Date: 2028-12-31

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.

Conditions

Leptomeningeal Metastases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

intrathecal injection of pemetrexed and double dose of vometinib

Group Type: EXPERIMENTAL

pemetrexed

Intervention Type: 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

Intervention Type: DRUG

double dose of vometinib (160mg)

Interventions

pemetrexed

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.

Intervention Type: DRUG

vometinib

double dose of vometinib (160mg)

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zhejiang Cancer Hospital

OTHER

Sponsor Role: lead

Responsible Party

Fan Yun, MD

Prof

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Countries

China

Central Contacts

Department of Thoracic Oncology, Zhejiang Cancer Hospital

Role: CONTACT

yusz@zjcc.org.cn

+86-0571-88122092

Facility Contacts

Yun Fan

Role: primary

yusz@zjcc.org.cn

+86-0571-88122092

Other Identifiers

ZhejiangCH-IRB-2024-1191(IIT)

Identifier Type: -

Identifier Source: org_study_id