Clinical trial NCT06861218: Cerebrospinal Fluid Cytology-guided Intrathecal Chemo-holiday Therapy for EGFR-positive NSCLC Leptomeningeal Metastases
Official title: Cerebrospinal Fluid Cytology-guided Intrathecal Chemo-holiday Therapy for EGFR-positive NSCLC Meningeal Metastases: a One-arm, Phase II Clinical Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Leptomeningeal Metastases
Keywords: Leptomeningeal Metastases
EGFR
Pemetrexed
intrathecal injection
vometinib
Lead sponsor: Zhejiang Cancer Hospital
Sponsor class: OTHER
First posted: 2025-03-06
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall survival
timeFrame: From the enrollment of this study until date of death from any cause, up to a maximum of approximately 2 years
Secondary outcomes:
measure: Impact on quality of life
timeFrame: 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.
measure: Clinical response rate
timeFrame: 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.
measure: leptomeningeal metastases related progression-free survival
timeFrame: 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.
measure: CSF cytological clearance
timeFrame: 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.
measure: Adverse events
timeFrame: 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.
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
References: