Leptomeningeal DiseaseGUIDE-CNSNCT07689721
ctDNA-Guided Intraventricular Therapy for CNS Malignancies
A study testing CSF ctDNA-Guided Clinical Management in people with Leptomeningeal Disease and Glioblastoma, run by Alireza Mansouri.
Trial summary
This prospective, single-center study will evaluate whether cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) testing using the Belay Summit assay can improve the clinical management of patients with malignant gliomas or brain metastases from non-small cell lung cancer (NSCLC) or breast cancer who are suspected… Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Leptomeningeal Disease, Glioblastoma, Brain Metastases
- What is being tested?
- CSF ctDNA-Guided Clinical Management
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 77 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2027to 1 Jan 2032
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years.
- Diagnosis of histologically or cytologically confirmed HER2+ breast cancer, or triple negative breast cancer, or Stage IV non-small cell lung cancer, or recurrent high-grade glioma).
- Undergoing clinically indicated cerebrospinal fluid (CSF) collection as part of routine clinical care: CSF may be obtained via lumbar puncture or existing CSF access device. Decision for CSF collection must be made independently by the treating clinical team and not solely for research purposes.
- Detectable CSF ctDNA and/or positive CSF cytology, with consideration for CNS-directed management by the treating neuro-oncology team.
- Ability to provide informed consent, or availability of a legally authorized representative (LAR).
Who cannot join
- Age <18 years.
- Inability to provide informed consent and no legally authorized representative (LAR) available.
- Not undergoing clinically indicated CSF collection as part of standard clinical care.
- Absence of detectable CSF ctDNA and absence of positive CSF cytology.
- Not being considered for CNS-directed management by the treating neuro-oncology team.
- Clinical contraindications to CSF collection, including but not limited to: Significant intracranial mass effect; (e.g., midline shift >5 mm or effacement of basal cisterns); Obstructive hydrocephalus or posterior fossa mass effect; Coagulopathy or bleeding risk precluding lumbar puncture or CSF access; Inability to safely obtain CSF access.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: ctDNA-Guided Intraventricular Therapy Trial: A Prospective Study in Patients With Malignant Gliomas or Brain Metastases From Non-Small Cell Lung Cancer and Breast Cancer
This prospective, single-center study will evaluate whether cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) testing using the Belay Summit assay can improve the clinical management of patients with malignant gliomas or brain metastases from non-small cell lung cancer (NSCLC) or breast cancer who are suspected of having central nervous system (CNS) disease. Patients undergoing clinically indicated CSF evaluation will receive standard clinical testing, including CSF cytology and the Belay Summit ctDNA assay. Treatment decisions will remain at the discretion of the treating multidisciplinary neuro-oncology team. The primary objective is to evaluate 6-month clinical CNS progression-free survival (cCNS-PFS), with secondary objectives assessing safety and the association between CSF ctDNA dynamics and clinical outcomes. Exploratory proteogenomic analyses will be performed on residual CSF specimens when sufficient sample is available.
Read the detailed description
Leptomeningeal disease (LMD) and other advanced CNS malignancies remain associated with poor prognosis and limited tools for monitoring disease activity and treatment response. Conventional CSF cytology has limited sensitivity, particularly in the early stages of disease. Circulating tumor DNA (ctDNA) analysis of cerebrospinal fluid has emerged as a promising liquid biopsy approach for detecting molecular evidence of CNS disease and monitoring treatment response.
This prospective, single-center investigator-initiated study will evaluate the clinical utility of the Belay Summit CSF ctDNA assay in patients with malignant gliomas or brain metastases from NSCLC or breast cancer undergoing clinically indicated CSF evaluation. Patients may be enrolled either before or after clinically indicated lumbar puncture, provided eligibility criteria are met. Clinical management, including consideration of Ommaya reservoir placement, intraventricular therapy, systemic therapy modification, radiation therapy, or other CNS-directed interventions, will remain at the discretion of the treating multidisciplinary neuro-oncology team. The study does not mandate treatment assignment based on ctDNA results.
- Conditions
- Leptomeningeal Disease, Glioblastoma, Brain Metastases, Non-Small Cell Lung Cancer, Breast Cancer
- Being tested
- CSF ctDNA-Guided Clinical Management
- Medical subject headings
- Meningeal Neoplasms, Glioblastoma, Brain Neoplasms, Carcinoma, Non-Small-Cell Lung, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CSF ctDNA-Guided Clinical ManagementDevice
Participants undergo clinically indicated cerebrospinal fluid (CSF) evaluation, including CSF cytology and the Belay Summit CSF circulating tumor DNA (ctDNA) assay. Results are incorporated into multidisciplinary neuro-oncology evaluation to inform CNS-directed clinical management. Treatment decisions, including intraventricular therapy, systemic therapy modification, radiation therapy, or other interventions, remain at the discretion of the treating physicians and are not mandated by the study protocol.
The primary objective is to evaluate cCNS-PFS at 6 months. Secondary objectives include evaluating the safety of CNS-directed management and assessing the relationship between longitudinal CSF ctDNA dynamics and clinical outcomes.
| Study group | Role | What they receive |
|---|---|---|
| ctDNA-Guided CNS Management | Experimental | Participants undergo clinically indicated cerebrospinal fluid (CSF) evaluation, including CSF cytology and the Belay Summit CSF circulating tumor DNA (ctDNA) assay. Clinical management is determined by the treating multidisciplinary neuro-oncology team based on the totality of clinical findings, including ctDNA results, imaging, CSF cytology, and neurologic assessment. Eligible participants are followed prospectively for clinical outcomes. Receives: Device: CSF ctDNA-Guided Clinical Management |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical central nervous system progression-free survival at 6 months (cCNS-PFS6)
Clinical CNS progression-free survival (cCNS-PFS6) will be assessed using the Neurologic Assessment in Neuro-Oncology Leptomeningeal Metastases (NANO-LM) scorecard. Disease progression will be determined by multidisciplinary adjudication based on neurologic assessment, radiographic findings, CSF cytology, and other relevant clinical information to distinguish leptomeningeal disease progression from alternative causes of neurologic deterioration.
Measured: 6 months
Secondary outcomes (2)
Incidence of treatment-related neurologic and procedure-related adverse events
Frequency and severity of clinically significant neurologic toxicities, Ommaya reservoir-related complications, CNS-directed therapy-related complications, treatment-related hospitalizations, and other clinically relevant adverse events, graded according to CTCAE version 5.0 where applicable.
Measured: From enrollment through 6 months
Change in cerebrospinal fluid circulating tumor DNA (CSF ctDNA) burden
Quantitative changes in CSF ctDNA variant allele frequency (VAF), including reduction or clearance of baseline VAF, and their association with clinical CNS progression-free survival. Exploratory analyses will evaluate whether a ≥50% reduction or complete clearance of baseline VAF is associated with durable clinical stability at 6 months.
Measured: Baseline, Month 3, and Month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2026
- Study start1 Jan 2027 (estimated)
- Primary completion1 Jul 2030 (estimated)
- Study completion1 Jan 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leptomeningeal DiseaseStudies 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 77 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Alireza Mansouri
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Alireza Mansouri, Milton S. Hershey Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07689721
- Sponsor's protocol ID
- PSCI-26-052
- Acronym
- GUIDE-CNS
- Status last verified
- Jul 2026
- First submitted
- 1 Jul 2026
- Last updated
- 8 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ctDNA-Guided Intraventricular Therapy Trial: A Prospective Study in Patients With Malignant Gliomas or Brain Metastases From Non-Small Cell Lung Cancer and Breast Cancer
- ClinicalTrials.gov ID
- NCT07689721
- Acronym / sponsor ID
- GUIDE-CNS / PSCI-26-052
- Conditions
- Leptomeningeal Disease, Glioblastoma, Brain Metastases, Non-Small Cell Lung Cancer, Breast Cancer
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 77 participants (estimated)
- Lead sponsor
- Alireza MansouriUniversity, hospital or other
- Study start
- 1 Jan 2027 (estimated)
- Primary completion
- 1 Jul 2030 (estimated)
- Study completion
- 1 Jan 2032 (estimated)
- First posted
- 8 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This prospective, single-center study will evaluate whether cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) testing using the Belay Summit assay can improve the clinical management of patients with malignant gliomas or brain metastases from non-small cell lung cancer (NSCLC) or breast cancer who are suspected of having central nervous system (CNS) disease. Patients undergoing clinically indicated CSF evaluation will receive standard clinical testing, including CSF cytology and the Belay Summit ctDNA assay. Treatment decisions will remain at the discretion of the treating multidisciplinary neuro-oncology team. The primary objective is to evaluate 6-month clinical CNS progression-free survival (cCNS-PFS), with secondary objectives assessing safety and the association between CSF ctDNA dynamics and clinical outcomes. Exploratory proteogenomic analyses will be performed on residual CSF specimens when sufficient sample is available.
Detailed description
Leptomeningeal disease (LMD) and other advanced CNS malignancies remain associated with poor prognosis and limited tools for monitoring disease activity and treatment response. Conventional CSF cytology has limited sensitivity, particularly in the early stages of disease. Circulating tumor DNA (ctDNA) analysis of cerebrospinal fluid has emerged as a promising liquid biopsy approach for detecting molecular evidence of CNS disease and monitoring treatment response.
This prospective, single-center investigator-initiated study will evaluate the clinical utility of the Belay Summit CSF ctDNA assay in patients with malignant gliomas or brain metastases from NSCLC or breast cancer undergoing clinically indicated CSF evaluation. Patients may be enrolled either before or after clinically indicated lumbar puncture, provided eligibility criteria are met. Clinical management, including consideration of Ommaya reservoir placement, intraventricular therapy, systemic therapy modification, radiation therapy, or other CNS-directed interventions, will remain at the discretion of the treating multidisciplinary neuro-oncology team. The study does not mandate treatment assignment based on ctDNA results.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ctDNA-Guided CNS Management | Experimental | Device: CSF ctDNA-Guided Clinical ManagementParticipants undergo clinically indicated cerebrospinal fluid (CSF) evaluation, including CSF cytology and the Belay Summit CSF circulating tumor DNA (ctDNA) assay. Clinical management is determined by the treating multidisciplinary neuro-oncology team based on the totality of clinical findings, including ctDNA results, imaging, CSF cytology, and neurologic assessment. Eligible participants are followed prospectively for clinical outcomes. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age ≥ 18 years.
- Diagnosis of histologically or cytologically confirmed HER2+ breast cancer, or triple negative breast cancer, or Stage IV non-small cell lung cancer, or recurrent high-grade glioma).
- Undergoing clinically indicated cerebrospinal fluid (CSF) collection as part of routine clinical care: CSF may be obtained via lumbar puncture or existing CSF access device. Decision for CSF collection must be made independently by the treating clinical team and not solely for research purposes.
- Detectable CSF ctDNA and/or positive CSF cytology, with consideration for CNS-directed management by the treating neuro-oncology team.
- Ability to provide informed consent, or availability of a legally authorized representative (LAR).
Key exclusion criteria (6 listed)
- Age <18 years.
- Inability to provide informed consent and no legally authorized representative (LAR) available.
- Not undergoing clinically indicated CSF collection as part of standard clinical care.
- Absence of detectable CSF ctDNA and absence of positive CSF cytology.
- Not being considered for CNS-directed management by the treating neuro-oncology team.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CSF ctDNA-Guided Clinical ManagementParticipants undergo clinically indicated cerebrospinal fluid (CSF) evaluation, including CSF cytology and the Belay Summit CSF circulating tumor DNA (ctDNA) assay. Results are incorporated into multidisciplinary neuro-oncology evaluation to inform CNS-directed clinical management. Treatment decisions, including intraventricular therapy, systemic therapy modification, radiation therapy, or other interventions, remain at the discretion of the treating physicians and are not mandated by the study protocol. The primary objective is to evaluate cCNS-PFS at 6 months. Secondary objectives include evaluating the safety of CNS-directed management and assessing the relationship between longitudinal CSF ctDNA dynamics and clinical outcomes. | Device | ctDNA-Guided CNS Management |
Primary outcome
Clinical central nervous system progression-free survival at 6 months (cCNS-PFS6)
Time frame: 6 months
Clinical CNS progression-free survival (cCNS-PFS6) will be assessed using the Neurologic Assessment in Neuro-Oncology Leptomeningeal Metastases (NANO-LM) scorecard. Disease progression will be determined by multidisciplinary adjudication based on neurologic assessment, radiographic findings, CSF cytology, and other relevant clinical information to distinguish leptomeningeal disease progression from alternative causes of neurologic deterioration.
2 secondary outcomes
Incidence of treatment-related neurologic and procedure-related adverse events
Time frame: From enrollment through 6 months
Change in cerebrospinal fluid circulating tumor DNA (CSF ctDNA) burden
Time frame: Baseline, Month 3, and Month 6
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A study testing CSF ctDNA-Guided Clinical Management in people with Leptomeningeal Disease and Glioblastoma, run by Alireza Mansouri.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 8 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Crystal Sowers (7175315471, psci-cto@pennstatehealth.psu.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical central nervous system progression-free survival at 6 months (cCNS-PFS6) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2026.