ctDNA-Guided Intraventricular Therapy for CNS Malignancies

NCT07689721 | Not Yet Recruiting DMC

• 1 other identifier: PSCI-26-052
• Study Type: interventional
• Target: 77
• Locations: 0 countries
• Sites: N/A

Brief 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 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.

Conditions

Leptomeningeal Disease; Glioblastoma; Brain Metastases; Non-Small Cell Lung Cancer; Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  6 months

Secondary Outcomes (2)

• Incidence of treatment-related neurologic and procedure-related adverse events

  From enrollment through 6 months

• Change in cerebrospinal fluid circulating tumor DNA (CSF ctDNA) burden

  Baseline, Month 3, and Month 6

Study Arms (1)

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.

Device: CSF ctDNA-Guided Clinical Management

Interventions

CSF ctDNA-Guided Clinical Management DEVICE

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.

ctDNA-Guided CNS Management

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alireza Mansouri: lead

MeSH Terms

Conditions

Meningeal Neoplasms; Glioblastoma; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Breast Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Diseases; Central Nervous System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Crystal Sowers

CONTACT

7175315471; psci-cto@pennstatehealth.psu.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Neurosurgery

Study Record Dates

• First Submitted: July 1, 2026
• First Posted: July 8, 2026
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): July 1, 2030
• Study Completion (Estimated): January 1, 2032
• Last Updated: July 8, 2026

Record last verified: 2026-07