CSF Analysis in EGFR Mutant Non-Small Cell Lung Cancer with Leptomeningeal Disease

Not Applicable

Recruiting

• Conditions: Leptomeningeal Metastasis; EGFR Activating Mutation; Non Small Cell Lung Cancer
• Interventions: Diagnostic Test: Lumbar puncture and Phlebotomy

• Registration Number: NCT05257967
• Lead Sponsor: British Columbia Cancer Agency

Brief Summary

Leptomeningeal disease is malignant seeding of the leptomeninges and presents with a variety of symptoms frequently impacting quality of life. With improvement in treatment options, rates of leptomeningeal disease are increasing and currently found in up to 9% of EGFR mutant NSCLC.

Systemic therapy may be more effective if it can target the correct molecular aberration. The molecular characterization of central nervous system disease may differ from disease outside of the central nervous system. The aim of this pilot trial is to evaluate for molecular differences between cerebral spinal fluid (CSF) and blood circulating tumor DNA (ctDNA) through the use of ddPCR and BC Cancer NGS panel molecular testing.

Detailed Description

The aim of this pilot trial is to evaluate the concordance/discordance of molecular profiling of CSF and plasma ctDNA after the development of leptomeningeal disease in EGFR mutant NSCLC. Patients with EGFR mutant NSCLC who develop leptomeningeal disease on a first, second or third generation tyrosine kinase inhibitor are potentially eligible for this clinical trial.

This is a prospective pilot study designed to accrue 10 patients. Baseline MRI brain and spine must be completed prior to enrolment to insure that a lumbar puncture can be completed safely. All eligible subjects will be consented for ddPCR and Canexia Follow It plasma and CSF based molecular testing. Patients will have baseline information collected and will complete baseline quality of life (QoL) questionnaires. QoL questionnaires will be obtained every 12 weeks +/- 2 weeks and survival will be measured through chart review. There will be no treatment intervention; however we will collect information on treatment received after enrolment in trial. Volume of leptomeningeal disease will be scored by number of gadolinium enhancing sites in 8 predetermined locations.

Study Timeline

• Study First Submitted: 2022-02-05
• Study First Submitted QC: 2022-02-24
• Study First Posted: 2022-02-25
• Study Start: 2022-07-18
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-08
• Last Update Posted: 2025-02-11
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

• Subject age is greater than or equal to 18 years at the time of signature of informed consent.
• Histologically or cytologically confirmed metastatic EGFR mutant NSCLC.
• Leptomeningeal disease based on brain MRI or CSF cytology.
• ECOG 0-3.
• Life expectancy of at least 8 weeks.
• Adequate hematologic and end organ function for testing.
• Ability to give informed consent for the study procedures defined in this protocol.

Exclusion Criteria

• Inability to undergo a lumbar puncture due to thrombocytopenia, bleeding disorders, as well as inability to cooperate or consent to procedure.
• Subjects who are otherwise felt by the treating clinician to be unfit to proceed with this protocol.
• MRI spine demonstrating spinal leptomeningeal disease preventing a safe lumbar puncture.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental arm	Lumbar puncture and Phlebotomy	ddPCR and BC Cancer NGS panel completed on cerebral spinal fluid and blood circulating tumor DNA

Primary Outcome Measures

Name	Time	Method
Concordance of molecular profiling of CSF and plasma in EGFR mutation positive NSCLC patients with leptomeningeal disease	36 months	To determine the concordance rate of molecular alterations detected in the CSF and plasma of EGFR mutation positive NSCLC patients with leptomeningeal disease

Secondary Outcome Measures

Name	Time	Method
Molecular profiling comparison	36 months	To assess concordance/discordance rates between ddPCR and Canexia Follow It completed on CSF and plasma based testing.
Concordance of treatment recommendations based on ctDNA and CSF	36 months	To determine the concordance and discordance between physician treatment recommendations based on ctDNA versus CSF molecular profiling.
Correlation between MRI and CSF	36 months	To correlate burden of leptomeningeal disease found on MRI and CSF positivity for tumor DNA.
Overall survival	36 months	To determine overall survival from time of developing leptomeningeal disease.
Molecular profiling descriptive comparison of patients treated with first/second generation versus 3rd generation EGFR TKIs	36 months	To identify molecular aberrations in the ctDNA and CSF of patients who progress on first/second EGFR TKIs and third generation EGFR TKIs to perform a descriptive comparison of shared and unique mutations identified based on prior exposure to first/second versus third generation EGFR TKI
Quality of life with leptomeningeal disease	36 months	To assess the quality of life using the validated instrument, EuroQol 5 Dimension (EQ5D) (Scale of 0-100 where 0 is worst health and 100 is best health)

Trial Locations

Locations (1)

BC Cancer; 🇨🇦 Vancouver, British Columbia, Canada