Clinical trial NCT05257967: CSF Analysis in EGFR Mutant Non-Small Cell Lung Cancer with Leptomeningeal Disease
Official title: CSF Liquid Biopsy Based Characterization of Leptomeningeal Disease in EGFR Mutant Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: EGFR Activating Mutation
Leptomeningeal Metastasis
Non Small Cell Lung Cancer
Keywords: non-small cell lung cancer
EGFR
leptomeningeal disease
Lead sponsor: British Columbia Cancer Agency
Sponsor class: OTHER
First posted: 2022-02-25
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Concordance of molecular profiling of CSF and plasma in EGFR mutation positive NSCLC patients with leptomeningeal disease
timeFrame: 36 months
Secondary outcomes:
measure: Concordance of treatment recommendations based on ctDNA and CSF
timeFrame: 36 months
measure: Molecular profiling comparison
timeFrame: 36 months
measure: Molecular profiling descriptive comparison of patients treated with first/second generation versus 3rd generation EGFR TKIs
timeFrame: 36 months
measure: Correlation between MRI and CSF
timeFrame: 36 months
measure: Overall survival
timeFrame: 36 months
measure: Quality of life with leptomeningeal disease
timeFrame: 36 months
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: BC Cancer
state: British Columbia
Study officials:
affiliation: BC Cancer
name: Cheryl Ho, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nevel KS, DiStefano N, Lin X, Skakodub A, Ogilvie SQ, Reiner AS, Pentsova E, Boire A. A retrospective, quantitative assessment of disease burden in patients with leptomeningeal metastases from non-small-cell lung cancer. Neuro Oncol. 2020 May 15;22(5):675-683. doi: 10.1093/neuonc/noz208.
citation: White MD, Klein RH, Shaw B, Kim A, Subramanian M, Mora JL, Giobbie-Hurder A, Nagabhushan D, Jain A, Singh M, Kuter BM, Nayyar N, Bertalan MS, Stocking JH, Markson SC, Lastrapes M, Alvarez-Breckenridge C, Cahill DP, Gydush G, Rhoades J, Rotem D, Adalsteinsson VA, Mahar M, Kaplan A, Oh K, Sullivan RJ, Gerstner E, Carter SL, Brastianos PK. Detection of Leptomeningeal Disease Using Cell-Free DNA From Cerebrospinal Fluid. JAMA Netw Open. 2021 Aug 2;4(8):e2120040. doi: 10.1001/jamanetworkopen.2021.20040.