EGFR Activating Mutation, Leptomeningeal Metastasis, Non Small Cell Lung Cancer
Conditions
Keywords
non-small cell lung cancer, EGFR, leptomeningeal disease
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.
Interventions
DIAGNOSTIC_TESTLumbar puncture and Phlebotomy
Sampling of cerebral spinal fluid and plasma.
Sponsors
British Columbia Cancer Agency
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Molecular profiling comparison | 36 months | To assess concordance/discordance rates between ddPCR and Canexia Follow It completed on CSF and plasma based testing. |
| 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 |
| 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. |
| Overall survival | 36 months | To determine overall survival from time of developing leptomeningeal disease. |
| 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) |
| Correlation between MRI and CSF | 36 months | To correlate burden of leptomeningeal disease found on MRI and CSF positivity for tumor DNA. |
Countries
Canada
Contacts
Primary ContactCheryl Ho, MD
Backup ContactBarbara Melosky, MD
Outcome results
None listed