Surgical Study on Upfront or Recurrent High-Grade Glioma (WHO Grade III and IV) Electrical Activity

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Prospective Surgical Study on Upfront or Recurrent High Grade Glioma (WHO Grade III and IV) Electrical Activity - Understanding Neuron-Glioma Interaction to Predict Progression

Conditions
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High Grade Glioma, Glioblastoma

Intervention / Treatment
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* Procedure: Standard Surgical Treatment
* Procedure: Intraoperative Electrocorticography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Appearance of high-grade glioma on magnetic resonance imaging History of histologically-confirmed diagnosis of glioma undergoing repeat resection of a recurrent/progressive tumor that is likely high-grade glioma Age ≥ 18 years old Volumetric MRI within 1 month before surgery Karnofsky performance status of 60 or higher The participant (or legally acceptable representative if applicable) provides written informed consent for the trial Considered an appropriate neurosurgical candidate based on screening/baseline laboratory values within 1 month before surgery 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 Pregnancy Coagulopathy or platelet dysfunction that increases the risk of intra and postoperative hemorrhage Tumor location requiring Depth Electrode 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Participants undergoing surgical resection will have a regional recording of neuronal electrical activity that will be measured in a minimum of 4 peritumoral anatomic zones via depth electrodes, overlying the cortex of the lesion via a subdural grid, within the presumed tumor, and in adjacent presumed normal brain. Recording findings specific to these anatomo-electro-clinical zones will be correlated with the presence/degree of contrast-enhancing tumor on MRI at recurrence. Additionally, biopsies will be obtained in these depth electrode regions for correlative studies.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard Surgical Treatment + Intraoperative Electrocorticography<br>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<br>* During this surgery, participants will also undergo a tissue biopsy at recording sites for correlation to neural recording data.<br>Procedure: Intraoperative Electrocorticography<br>* Each participant will undergo intraoperative electrocorticography (ECOG) through subdural grid (SDG) and depth electrode (DE) via FDA-cleared, standardized, brain recording technology.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility (Avoidance of unacceptable events) | The primary aim is feasibility. This is defined as having 1 or fewer of the 10 participants recovery without experiencing unacceptable events. Unacceptable events are defined as two or more of the following during the window of observation (30 days): Intracranial Hemorrhage (grade 2 or higher [CTCAE v5.0]); or, Wound Infection (grade 3 or higher [CTCAE v5.0]). | 30 days post surgery | 
| No evidence of intracranial hemorrhage (grade 3 or higher) | This will be assessed via post-operative imaging and a physical exam. | 1-3 days post surgery | 
| No evidence of wound infection (grade 3 or higher) | Physical assessment of surgical site. | 10-14 days 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High Grade Glioma, Glioblastoma, Neural Recording, Electrical Activity