Prospective Surgical Study on the Pattern of Electrical Activity in High Grade Glioma as a Predictor of Progression

Prospective Surgical Study on the Pattern of Electrical Activity in High Grade Glioma (WHO Grade III and IV) as a Predictor of Progression

The purpose of this study is to test the safety and feasibility of recording brain activity within and around high-grade glioma tumors at the time of surgery. A small biopsy will be taken at the sites of the recordings.

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma; High Grade Glioma
• Intervention / Treatment: Procedure: Standard Surgical Treatment; Procedure: Intraoperative Electrocorticography

Detailed Description

High-grade gliomas are incurable primary brain tumors. Recent data support that glioma cells can integrate within neuronal circuits. Glioma cells and neurons communicate via electrical impulses and chemically, through neurotransmitters. This crosstalk has been shown to promote glioma cell migration and invasion in preclinical models. However, the nature of the electrical activity and underlying molecular mechanisms are poorly understood. The long-term goal of this study is to determine the impact of high electrical activity and pattern of activity on tumor invasion, and mechanistic basis of its regulation and functional consequences. This phase I safety and feasibility study is being proposed as a first step toward dissecting the connection between electrical activity and glioma behavior. The goal is to determine the safety and feasibility of recording electrical activity in the tumor-neuron interface using technologies that are already being used clinically for participants undergoing brain surgery.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jennifer Yu, MD, PhD; Phone Number: 1-866-223-8100; Email: taussigresearch@ccf.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
      • Contact: Jennifer Yu, MD, PhD; Phone Number: 866-223-8100; Email: taussigresearch@ccf.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants who have the appearance of high-grade glioma (HGG, WHO Grade 3 and 4, including GBM) on MR imaging are allowed to consent and will undergo the procedure if the frozen is consistent with HGG

OR

• Participants with a history of histologically-confirmed diagnosis of high- grade glioma that are undergoing resection of a recurrent/progressive tumor that is likely recurrent/progressive high- grade glioma as identified on preoperative MR imaging
• Age ≥ 18 years old
• Volumetric MRI within 1 month prior to surgery
• Karnofsky performance status of 60 or higher
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.

• Participants must be considered appropriate neurosurgical candidates with the following screening/baseline laboratory values within 1 month prior to surgery:

  • Absolute neutrophil count ≥ 1500/µL
  • Platelets ≥ 100 000/µL
  • International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × Upper limit of normal (ULN) unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
  • Urine or Serum Pregnancy Test = Negative (Not applicable to participants with bilateral oophorectomy and/or hysterectomy or to those participants who are postmenopausal).

Exclusion Criteria:

• Severe co-morbidity that would confer excess risk of surgery as determined by the treating physician.
• Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy.
• Is pregnant
• Coagulopathy or platelet dysfunction that increases the risk of intra and postoperative hemorrhage
• Tumor location requiring DE placement/biopsy in eloquent or critical region of the brain (e.g. primary motor and sensory cortices, speech and vision centers, thalamus, basal ganglia, cerebellum, brain stem) as deemed by the neurosurgeon designing the surgical plan

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: Standard Surgical Treatment + Intraoperative Electrocorticography; Each participant will undergo intraoperative electrocorticography (ECOG) through subdural grid (SDG) and depth electrode (DE) via FDA-cleared, standardized, brain recording technology. During this surgery, participants will also undergo a tissue biopsy at recording sites for correlation to neural recording data.

Procedure: Standard Surgical Treatment; During this surgery, participants will also undergo a tissue biopsy at recording sites for correlation to neural recording data.; Procedure: Intraoperative Electrocorticography; Each participant will undergo intraoperative electrocorticography (ECOG) through subdural grid (SDG) and depth electrode (DE) via FDA-cleared, standardized, brain recording technology.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between electrical activity and anatomic region of progression based on follow-up contrast-enhanced MRI	To describe the pattern of electrical activity (neuronal hyperexcitability) in brain surrounding the enhancing tumor during open surgery in patients with high grade gliomas and its correlation with progression	Up to 9 months post surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Predict the area of progression in the peri-resection region of High Grade Gliomas based on electrical activity near the interface of the tumor and normal brain	A correlation will be performed between electrical activity and anatomic region of progression based on follow-up contrast-enhanced MRI. Electrical activity will be defined as the regional mean high-gamma band power at measured at each peritumoral anatomic zone via DE. Serial MRIs will be performed in the outpatient setting through the disease course as is standard of care. These MRIs will be assessed for tumor progression per Response Assessment in Neuro-Oncology (RANO) guidelines. At the time of tumor progression, the geographic region of progression on the imaging will be compared to regional mean high-gamma band power for any statistically significant correlations. Tumor progression will be defined as binary (yes/no) within a time window post-surgery for each peri-resection region.	1 day post surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between electrical activity (neuronal hyperexcitability) in brain surrounding the enhancing tumor and cellular and molecular profile of the tumor and its microenvironment	Electrical activity will be assessed as described above and correlated with transcriptomic changes. Bioinformatics analyses including gene ontology analyses and multi-dimensional network analyses will be performed.	At study completion, an aim for 1 year post treatment

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Collaborators: Burkhardt Brain Tumor and Neuro-Oncology Center
• Investigators: Principal Investigator: Jennifer Yu, MD, PhD, Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: September 29, 2022
• First Submitted That Met QC Criteria: September 30, 2022
• First Posted (Actual): October 4, 2022

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: High Grade Glioma; Glioblastoma; Neural Recording; Electrical Activity
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Glioma
• Other Study ID Numbers: CASE4321

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Aggregate data will be shared, while individual data will not need to be shared.

Drug and device information, study documents

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