Spinal fluid and blood liquid biopsy for people with metastatic solid tumors with or without brain involvement

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 will test whether a one-time spinal fluid (CSF) and blood sample can find tumor DNA in people with metastatic solid tumors, including those with brain metastases or leptomeningeal disease.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sunnybrook Health Sciences Centre (Academic / other)
• Locations: 1 site (Toronto, Ontario)
• Trial ID: NCT07476781 on ClinicalTrials.gov

What this trial studies

This prospective, single-centre feasibility project at Sunnybrook collects a one-time CSF sample (via lumbar puncture or Ommaya reservoir) and concurrent blood for plasma-based liquid biopsy from three predefined cohorts: leptomeningeal disease, parenchymal brain metastases without LMD, and no CNS metastases. Investigators will measure CSF cytology, circulating tumor DNA (ctDNA), and circulating tumor cells (CTCs), compare those results to plasma, and determine the proportion of patients with detectable CSF biomarkers in each cohort. The study will also explore CSF proteomic analysis in patients with positive CSF biomarkers and possibly extend proteomics to biomarker-negative samples if feasible. The goal is to define feasibility and the added value of CSF versus plasma for detecting CNS tumor-derived signals.

Who should consider this trial

Good fit: Adults with a metastatic solid tumor who either have leptomeningeal disease, have parenchymal brain metastases without LMD, or have no CNS metastases, and who can safely undergo lumbar puncture or have an accessible Ommaya reservoir are eligible.

Not a fit: Patients who cannot safely have CSF collected (unable to undergo lumbar puncture or lacking an accessible Ommaya reservoir) or whose tumors do not shed detectable DNA into CSF are unlikely to benefit.

Why it matters

Potential benefit: If successful, this approach could provide more accurate detection and molecular profiling of central nervous system tumor involvement to help guide treatment decisions.

How similar studies have performed: Prior small studies have shown CSF ctDNA can more sensitively reflect CNS disease than plasma in some settings, but comprehensive feasibility across multiple CNS involvement patterns remains limited.

Eligibility criteria

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)

Where this trial is running

Toronto, Ontario

• Sunnybrook Health Sciences Centre — Toronto, Ontario, Canada (Recruiting)

Study contacts

• Study coordinator: Katarzyna Jerzak, Dr

Conditions Solid Tumor Malignancies; Brain Metastasases; Leptomeningeal Disease