Glioma Supra Marginal Incision Trial

Study Overview
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Brief Summary
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G-SUMIT is a pilot, phase II,randomized controlled trial to evaluate the feasibility of performing a large-scale trial in patients undergoing surgery for first-time diagnosis of high grade glioma (HGG) in a surgically favorable anatomical location to answer the following: Does extending the margin of resection 1 cm beyond visible enhanced volume on MRI result in (a) an increase in overall survival? (b) result in a similar rate of clinically-significant neurological worsening during 30 days post surgery and quality of life at 6 and 12 months?

Detailed Description
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This pilot, multi-centre, pragmatic randomized controlled trial is planned to simulate all aspects of a larger definitive trial comparing conventional versus supramarginal tumor resection at the time of the first surgical resection of HGG in appropriately selected patients. This pilot will help determine the ability to meet pre-specified criteria in identification, recruitment, and patient allocation, allow for refinement of eligibility criteria for optimal recruitment, confirm safety of procedure and ability to retain participants for the duration of the trial. Preliminary efficacy data will inform sample size calculations and estimation of resources required for the envisioned larger definitive trial.

Official Title
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Phase II Pilot Randomized Controlled Trial to Assess Feasibility of Supra-marginal Surgical Resection of Malignant Glioma

Conditions
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High Grade Glioma

Intervention / Treatment
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* Procedure: Supramarginal resection
* Procedure: Conventional (i.e. GTR) resection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Radiographic evidence of a GAD-enhancing intra-axial tumor consistent with HGG; Age ≥18 ≤ 85 years; Karnofsky Performance Score ≥ 60; Location of tumor in a safe anatomical location and Patient or substitute decision maker (SDM) able to understand and consent to study participation. Exclusion Criteria: Multi-focal tumor, gliomatosis cerebri (≥3 lobes of the brain affected), tumors crossing the midline, or leptomeningeal enhancement; Previous craniotomy for tumor excision (stereotactic biopsy is permitted); Known metastatic cancer; Uncorrectable coagulopathy; Unable to obtain GAD-enhanced brain MRI.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Supramarginal resection (intervention arm)<br>Planned resection beyond the Gadolinium (GAD)-enhancing region extending to either at least 1 cm into non-enhancing tissue, or the nearest non-enhancing sulcal boundary/ventricle wall if these structures are closer than 1 cm. | Procedure: Supramarginal resection<br>* Tissue removal beyond the GAD-enhancing region extending to either at least 1 cm into non-enhancing tissue, or the nearest non-enhancing sulcal boundary/ventricle wall if these structures are closer than 1 cm.<br>|
| Other: Conventional (i.e. GTR) resection<br>Planned resection of ≥95% of the GAD-enhancing regions of tumor without expanding the resection beyond this margin. | Procedure: Conventional (i.e. GTR) resection<br>* Planned resection of ≥95% of the GAD-enhancing regions of tumor without expanding the resection beyond this margin.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Enrollment | The number of patients enrolled and successfully allocated to the intervention versus the control treatment | Collected at time of randomization, through end of enrollment period (2 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility using eligibility | Measures feasibility. Among all screened patients, the proportion of patients who meet the eligibility criteria | Screening/Enrollment | 
| Feasibility using proportion of consent | Measures feasibility. Among all screened patients, the proportion of patients consenting to participate | Screening/Enrollment | 
| Feasibility using number of completed visits | Measures feasibility. Among all screened patients, the proportion of patients completing all scheduled follow-up assessments | Through study completion, on average 2 years | 
| Feasibility using Gross Total Resection | Measures feasibility. The proportion of radiographically-confirmed gross total resection of contrast-enhancing tumor based on the first MRI after surgery. | 2 days (+/- 1 day) post surgery | 
| Efficacy using overall survival | Measures efficacy. The date of death will be obtained from hospital records, outpatient follow up clinic notes, or provincial cancer registries. | 6 weeks (+/- 2 weeks), 6 months (+/- 2 weeks) and 12 (+/- 1) months post surgery | 
| Efficacy using progression-free survival | Measures efficacy. Assessment of progression-free survival based on the Modified Criteria for Radiographic Response Assessment in Glioblastoma (mRANO) criteria. The date of death will be obtained from hospital records, outpatient follow up clinic notes, or provincial cancer registries. Progression-free survival will be measured based on mRANO criteria during regular 3-month interval clinical and MRI follow up | 6 weeks (+/- 2 weeks), 6 months (+/- 2 weeks) and 12 (+/- 1) months post surgery | 
| Safety using neurological function | The NIH Stroke Scale (NIHSS) will be used to assess neurological function. The NIHSS is a validated neurologically-specific outcome tool originally developed for rapid grading of stroke symptoms adopted in surgical clinical trials as well. | 2 (+/- 1) days and 6 weeks (+/- 2 weeks), days post surgery | 
| Safety using global disability | The modified rankin scale (mRS ) is a measure of global disability that has been widely used to assess outcome after stroke. The scale consists of six grades from 0 (no symptoms) to 5 (severe disability); 6 indicates death. | 6 months (+/- 2 weeks) and 12 (+/- 1) months post surgery | 
| Safety using quality of life | The overall quality of life will be assessed either in-person or over the phone using the EuroQol-5 (EQ-5D). The EQ-5D is a generic instrument used to measure quality of life, designed for self-completion by respondents either face-to-face or over telephone interview, also available in proxy version through care giver. | 6 months (+/- 2 weeks) and 12 (+/- 4 weeks) post surgery, 24 (+/- 4 weeks) post surgery | 
| Safety using 6 weeks (+/- 2 weeks) all cause-mortality | Will collect mortality data. | 6 weeks (+/- 2 weeks) post surgery | 
| Radiological | Volumetric measurement of contrast enhancement on MRI | 2 (+/- 1) days, 6 months (+/- 2 weeks) and 12 (+/- 1) months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Supramarginal resection, Standard total resection, Surgery, Brain tumor, HGG