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

NCT05257967 | Recruiting

• 1 other identifier: LUEGFRLM
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

EGFR Activating Mutation; Leptomeningeal Metastasis; Non Small Cell Lung Cancer

Keywords

non-small cell lung cancer; EGFR; leptomeningeal disease

Outcome Measures

Primary Outcomes (1)

• 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

  36 months

Secondary Outcomes (6)

• Concordance of treatment recommendations based on ctDNA and CSF

  36 months

• Molecular profiling comparison

  36 months

• Molecular profiling descriptive comparison of patients treated with first/second generation versus 3rd generation EGFR TKIs

  36 months

• Correlation between MRI and CSF

  36 months

• Overall survival

  36 months

Study Arms (1)

Experimental arm

EXPERIMENTAL

ddPCR and BC Cancer NGS panel completed on cerebral spinal fluid and blood circulating tumor DNA

Diagnostic Test: Lumbar puncture and Phlebotomy

Interventions

Lumbar puncture and Phlebotomy DIAGNOSTIC_TEST

Sampling of cerebral spinal fluid and plasma.

Experimental arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• British Columbia Cancer Agency: lead

Study Sites (1)

BC Cancer

Vancouver, British Columbia, V5Z4E6, Canada

RECRUITING

Related Publications (2)

• 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.

  PMID: 32352148 BACKGROUND

• 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.

  PMID: 34369989 BACKGROUND

MeSH Terms

Conditions

Meningeal Carcinomatosis; Carcinoma, Non-Small-Cell Lung; Meningeal Neoplasms

Interventions

Spinal Puncture; Phlebotomy

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Biopsy; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques; Blood Specimen Collection

Study Officials

• Cheryl Ho, MD

  BC Cancer

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cheryl Ho, MD

CONTACT

604.877.6000; cho@bccancer.bc.ca

Barbara Melosky, MD

CONTACT

604.877.6000

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prinicipal Investigator

Study Record Dates

• First Submitted: February 5, 2022
• First Posted: February 25, 2022
• Study Start: July 18, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 11, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)