Back to resultsSurgical Study on Upfront or Recurrent High-Grade Glioma (WHO Grade III and IV) Electrical Activity
Primary Purpose
High Grade Glioma, Glioblastoma
Status
Not yet recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Standard Surgical Treatment
Intraoperative Electrocorticography
Sponsored by
About this trial
This is an interventional treatment trial for High Grade Glioma focused on measuring High Grade Glioma, Glioblastoma, Neural Recording, Electrical Activity
Eligibility Criteria
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
Sites / Locations
- Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Standard Surgical Treatment + Intraoperative Electrocorticography
Arm Description
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.
Outcomes
Primary Outcome Measures
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]).
No evidence of intracranial hemorrhage (grade 3 or higher)
This will be assessed via post-operative imaging and a physical exam.
No evidence of wound infection (grade 3 or higher)
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
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.
Full Information
NCT ID
NCT05565118
First Posted
September 29, 2022
Last Updated
October 4, 2023
Sponsor
Case Comprehensive Cancer Center
1. Study Identification
Unique Protocol Identification Number
NCT05565118
Brief Title
Surgical Study on Upfront or Recurrent High-Grade Glioma (WHO Grade III and IV) Electrical Activity
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
April 1, 2024 (Anticipated)
Primary Completion Date
July 1, 2024 (Anticipated)
Study Completion Date
July 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Case Comprehensive Cancer Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
High Grade Glioma, Glioblastoma
Keywords
High Grade Glioma, Glioblastoma, Neural Recording, Electrical Activity
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
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)
Allocation
N/A
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Standard Surgical Treatment + Intraoperative Electrocorticography
Arm Type
Experimental
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Standard Surgical Treatment
Intervention Description
During this surgery, participants will also undergo a tissue biopsy at recording sites for correlation to neural recording data.
Intervention Type
Procedure
Intervention Name(s)
Intraoperative Electrocorticography
Intervention Description
Each participant will undergo intraoperative electrocorticography (ECOG) through subdural grid (SDG) and depth electrode (DE) via FDA-cleared, standardized, brain recording technology.
Primary Outcome Measure Information:
Title
Feasibility (Avoidance of unacceptable events)
Description
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]).
Time Frame
30 days post surgery
Title
No evidence of intracranial hemorrhage (grade 3 or higher)
Description
This will be assessed via post-operative imaging and a physical exam.
Time Frame
1-3 days post surgery
Title
No evidence of wound infection (grade 3 or higher)
Description
Physical assessment of surgical site.
Time Frame
10-14 days post surgery
Secondary Outcome Measure Information:
Title
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
Description
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.
Time Frame
1 day post surgery
Other Pre-specified Outcome Measures:
Title
Determine the correlation between peritumoral electrical activity (neuronal hyperexcitability) and degree of tumor infiltration.
Description
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.
Time Frame
At study completion, an aim for 1 year post treatment
Title
Determine the effect of peritumoral electrical activity (neuronal hyperexcitability) on the peritumoral immune microenvironment.
Description
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.
Time Frame
At study completion, an aim for 1 year post treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jennifer Yu, MD, PhD
Phone
1-866-223-8100
Email
taussigresearch@ccf.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jennifer Yu, MD, PhD
Organizational Affiliation
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jennifer Yu, MD, PhD
Phone
866-223-8100
Email
taussigresearch@ccf.org
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Aggregate data will be shared, while individual data will not need to be shared.
Learn more about this trial
Surgical Study on Upfront or Recurrent High-Grade Glioma (WHO Grade III and IV) Electrical Activity
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