Exploring the Feasibility of Cerebrospinal Fluid (CSF) and Blood Plasma Liquid Biopsy in Patients With Metastatic Solid Tumours and Primary Central Nervous System (CNS) Tumours: A Pilot Study

Overview

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).

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, in addition to primary CNS tumors. Four predefined cohorts will be studied: patients with leptomeningeal disease (Cohort A), patients with active parenchymal brain metastases (BrM) (Cohort B), patients without evidence of BrM (Cohort C), and patients with primary CNS tumours (Cohort D). 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 and circulating tumor DNA (ctDNA) in each cohort.

Aim 2: To compare ctDNA 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). If successful, the investigators will explore proteomic analyses in CSF biomarker negative patients to potentially identify more sensitive signatures for CNS metastasis detection.

Interventions

• 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).

Primary outcome measures

• Number of patients with positive cerebrospinal fluid (CSF) biomarkers in each cohort. [Time frame: From enrollment to the CSF and plasma collection, within 2-4 weeks]

Eligibility criteria

Inclusion criteria

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

• Patients in Cohort A will have previously untreated or progressing leptomeningeal metastatic disease (LMD) with or without parenchymal brain metastases (BrM).
• Patients in Cohort B will have previously untreated or BrM but no evidence of LMD.
• Patients in Cohort C will have progressing extra-cranial metastatic disease with no LMD or BrM.
• Patients in Cohort D will have primary CNS tumours (such as, but not limited to, meningioma, glioblastoma, astrocytoma, ependymoma, and other rare histologies).
• 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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

Canada · 1 center

• Sunnybrook Health Sciences Centre — Toronto

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. PMID 39704899

Identifiers

NCT: NCT07476781 · REB 6840

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗