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

Sponsor

Case Comprehensive Cancer Center (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05565118

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
High Grade Glioma Glioblastoma	Procedure: Standard Surgical Treatment Procedure: Intraoperative Electrocorticography	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention 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.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)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Jan 1, 2024

Anticipated Study Completion Date :

Jan 1, 2025

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Feasibility (Avoidance of unacceptable events) [30 days post surgery]
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]).
No evidence of intracranial hemorrhage (grade 3 or higher) [1-3 days post surgery]
This will be assessed via post-operative imaging and a physical exam.
No evidence of wound infection (grade 3 or higher) [10-14 days post surgery]
Physical assessment of surgical site.

Secondary Outcome Measures

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 [1 day post surgery]
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.

Other Outcome Measures

Determine the correlation between peritumoral electrical activity (neuronal hyperexcitability) and degree of tumor infiltration. [At study completion, an aim for 1 year post treatment]
Electrical activity will be defined as the regional mean high-gamma band power measured at each peritumoral anatomic zone via DE. The extent of and quality of electrical activity will be compared between different areas of recording (peritumoral area, tumor center, presumed uninvolved brain) and correlated with areas of invasion found on subsequent magnetic resonance imaging. The high-gamma power obtained at each site for a fixed time window will be processed to compare the activity in the peritumoral site and normal tissue. Signals will be analyzed for the presence of artifacts. A linear mixed model will be used to associate high-gamma band power with percent infiltration at the biopsy site level.
Determine the effect of peritumoral electrical activity (neuronal hyperexcitability) on the peritumoral immune microenvironment. [At study completion, an aim for 1 year post treatment]
Cell frequency of myeloid-derived stem cells (MDSCs), CD8+ T-cells, CD4+ T-cells and T-regulatory cells will be determined by flow cytometry analysis and transcriptomics of each biopsy site. At each time point, the frequency of these cell types will be reported as a percentage of the total number of white blood cells and as absolute numbers for each participant at each site.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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