CSF and Blood Plasma Liquid Biopsy in Patients With Metastatic Solid Tumours and CNS Metastases or no CNS Metastases

Exploring the Feasibility of Cerebrospinal Fluid (CSF) Liquid Biopsy in Patients With Metastatic Solid Tumours and Leptomeningeal Disease (Cohort A), Parenchymal Brain Metastases (Cohort B), or No Evidence of Central Nervous System (CNS) Metastases (Cohort C): A Pilot Study

This is a prospective, single-centre feasibility study of CSF ctDNA conducted at the Sunnybrook Odette Cancer Centre (SOCC), Toronto, Canada, including multiple solid tumor, stratified into cohorts according to CNS disease involvement, including leptomeningeal disease (Cohort A), parenchymal brain metastases (Cohort B), and no evidence of CNS metastases (Cohort C).

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor Malignancies; Leptomeningeal Disease (LMD); Brain Metastasases
• Intervention / Treatment: Procedure: One time CSF and blood sample

Detailed Description

Current plasma-based liquid biopsy approaches have limited ability to reflect CNS disease in patients with solid tumor. Since CSF is in direct contact with CNS disease, CSF analysis may provide more relevant biological information; however, its role as a liquid biopsy source has not been well characterized across different patterns of CNS involvement.

The goal of this pilot study is to evaluate the feasibility and utility of CSF-based liquid biopsy in patients with solid tumor with and without CNS metastases. Three predefined cohorts will be studied: patients with leptomeningeal disease (Cohort A), patients with active parenchymal brain metastases (Cohort B), and patients without evidence of parenchymal brain metastases (Cohort C). Participants will undergo a one-time CSF collection via lumbar puncture or Ommaya reservoir, with concurrent collection of peripheral blood for plasma-based liquid biopsy.

Aim 1: To determine the proportion of patients with positive CSF biomarkers, including cytology, circulating tumor DNA (ctDNA), and circulating tumor cells (CTCs), in each cohort.

Aim 2: To compare ctDNA and CTC results obtained from CSF with those obtained from plasma in each cohort.

Aim 3: To evaluate the feasibility of performing proteomic analysis using CSF samples in patients with at least one positive CSF biomarker (cytology and/or ctDNA and/or CTCs). If successful, the investigators will explore proteomic analyses in CSF biomarker negative patients to potentially identify more sensitive signatures for CNS metastasis detection.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Katarzyna Jerzak, Dr; Phone Number: 416-480-5000; Email: katarzyna.jerzak@sunnybrook.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M8Z 3X1
      • Recruiting
      • Sunnybrook Health Sciences Centre
      • Contact: Katarzyna Jerzak, Dr; Phone Number: 416-480-5000; Email: katarzyna.jerzak@sunnybrook.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosed with a metastatic solid tumour in one of the following scenarios:

  1. Patients in Cohort A will have leptomeningeal metastatic disease (LMD) with or without parenchymal brain metastases.
  2. Patients in Cohort B will have parenchymal brain metastases but no evidence of LMD.
  3. Patients in Cohort C will have metastatic solid tumours no CNS metastases (i.e. no LMD nor brain metastases).
• Patient is suitable for lumbar puncture and/or has an Ommaya reservoir that is accessible for CSF collection.
• Patient is eligible at any time point in their treatment course, including whether or not they have already started treatment for LMD. Considering the poor prognosis associated with LMD, rapid clinical deterioration, and the fact that available local and systemic therapies have not been shown to completely eradicate LMD, there is a high likelihood of detecting CSF biomarkers regardless of the timing of assessment. This flexible enrollment strategy is particularly important to support feasibility and recruitment in this less common and clinically challenging population. However, efforts will be made to collect CSF samples prior to treatment initiation and/or at the time of disease progression whenever possible.
• Patients with active brain metastases, defined as newly diagnosed and previously untreated lesions, or lesions that were previously treated and are now progressing.
• Patients who were previously enrolled in the study and had negative CSF biomarkers may be re-enrolled at a later time point (e.g., upon progression of CNS disease).

Exclusion Criteria:

• Inability to understand or unwillingness to provide written informed consent (language barriers are not exclusionary; the use of a translator is permitted).
• Patients with contraindications to lumbar puncture (e.g., infection at the LP site, uncontrolled bleeding diathesis > 1.5], severe thrombocytopenia [platelet count <40,000/µL], use of anticoagulant or antiplatelet medications cannot be safely interrupted, significant mass effect with risk of herniation, or presence of vertebral hardware)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CSF and Blood collection; All the patients will perform the same intervention (One-time CSF and blood sample)	Procedure: One time CSF and blood sample; One-time CSF collective via lumbar puncture or Ommaya reservoir and collection of concurrent plasma of peripheral blood (liquid biopsy).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To estimate the proportion of patients with solid tumours and CNS metastases (either meeting criteria for Cohort A or B), or no CNS metastases (Cohort C) who have positive CSF cytology, positive ctDNA, and/or positive CTCs	From enrollment to the CSF and plasma collection, within 2-4 weeks

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre

Publications and helpful links

General Publications

• Zhu JW, Shum M, Qazi MA, Sahgal A, Das S, Dankner M, Menjak I, Lim-Fat MJ, Jerzak KJ. Cerebral spinal fluid analyses and therapeutic implications for leptomeningeal metastatic disease. J Neurooncol. 2025 Mar;172(1):31-40. doi: 10.1007/s11060-024-04902-0. Epub 2024 Dec 20.

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: March 3, 2026
• First Submitted That Met QC Criteria: March 12, 2026
• First Posted (Actual): March 17, 2026

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Meningeal Neoplasms; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: REB 6840

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No