EGFR Activating MutationNCT05257967
CSF Analysis in EGFR Mutant Non-Small Cell Lung Cancer With Leptomeningeal Disease
A study testing Lumbar puncture and Phlebotomy in people with EGFR Activating Mutation and Leptomeningeal Metastasis, run by British Columbia Cancer Agency at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- EGFR Activating Mutation, Leptomeningeal Metastasis, Non Small Cell Lung Cancer
- What is being tested?
- Lumbar puncture and Phlebotomy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteCanada
- Study dates
- 18 Jul 2022to 31 Dec 2027
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Barbara Melosky, MD contact
Canada1 site, 1 recruiting
- Recruiting
BC Cancer
Vancouver, British Columbia, V5Z4E6
Cheryl Ho, MD, 604-877-6000
About this study
Official title: CSF Liquid Biopsy Based Characterization of Leptomeningeal Disease in EGFR Mutant Non-Small Cell Lung Cancer
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.
Read the 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.
- Being tested
- Lumbar puncture and Phlebotomy
- Keywords
- non-small cell lung cancer, EGFR, leptomeningeal disease
- Medical subject headings
- Meningeal Carcinomatosis, Carcinoma, Non-Small-Cell Lung, Meningeal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lumbar puncture and PhlebotomyDiagnostic test
Sampling of cerebral spinal fluid and plasma.
| Study group | Role | What they receive |
|---|---|---|
| Experimental arm | Experimental | ddPCR and BC Cancer NGS panel completed on cerebral spinal fluid and blood circulating tumor DNA Receives: Diagnostic Test: Lumbar puncture and Phlebotomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Concordance of molecular profiling of CSF and plasma in EGFR mutation positive NSCLC patients with leptomeningeal disease
To determine the concordance rate of molecular alterations detected in the CSF and plasma of EGFR mutation positive NSCLC patients with leptomeningeal disease
Measured: 36 months
Secondary outcomes (6)
Concordance of treatment recommendations based on ctDNA and CSF
To determine the concordance and discordance between physician treatment recommendations based on ctDNA versus CSF molecular profiling.
Measured: 36 months
Molecular profiling comparison
To assess concordance/discordance rates between ddPCR and Canexia Follow It completed on CSF and plasma based testing.
Measured: 36 months
Molecular profiling descriptive comparison of patients treated with first/second generation versus 3rd generation EGFR TKIs
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
Measured: 36 months
Correlation between MRI and CSF
To correlate burden of leptomeningeal disease found on MRI and CSF positivity for tumor DNA.
Measured: 36 months
Overall survival
To determine overall survival from time of developing leptomeningeal disease.
Measured: 36 months
Quality of life with leptomeningeal disease
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)
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2022
- Study start18 Jul 2022
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for EGFR Activating MutationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- British Columbia Cancer Agency
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Cheryl, British Columbia Cancer Agency
- Investigators
- Cheryl Ho, MD, Principal investigator, BC Cancer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05257967
- Sponsor's protocol ID
- LUEGFRLM
- Status last verified
- Oct 2026
- First submitted
- 5 Feb 2022
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 34369989Nevel 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.
PubMed 32352148