High Grade Glioma
Conditions
Keywords
Supramarginal resection, Standard total resection, Surgery, Brain tumor, HGG
Brief summary
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
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.
Interventions
PROCEDURESupramarginal resection
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.
PROCEDUREConventional (i.e. GTR) resection
Planned resection of ≥95% of the GAD-enhancing regions of tumor without expanding the resection beyond this margin.
Sponsors
Sunnybrook Health Sciences Centre
Canadian Institutes of Health Research (CIHR)
Sunnybrook Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Radiographic evidence of a GAD-enhancing intra-axial tumor consistent with HGG; 2. Age ≥18 ≤ 85 years; 3. Karnofsky Performance Score ≥ 60; 4. Location of tumor in a safe anatomical location and 5. Patient or substitute decision maker (SDM) able to understand and consent to study participation.
Exclusion criteria
1. Multi-focal tumor, gliomatosis cerebri (≥3 lobes of the brain affected), tumors crossing the midline, or leptomeningeal enhancement; 2. Previous craniotomy for tumor excision (stereotactic biopsy is permitted); 3. Known metastatic cancer; 4. Uncorrectable coagulopathy; 5. Unable to obtain GAD-enhanced brain MRI.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Enrollment | Collected at time of randomization, through end of enrollment period (2 years) | The number of patients enrolled and successfully allocated to the intervention versus the control treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety using 6 weeks (+/- 2 weeks) all cause-mortality | 6 weeks (+/- 2 weeks) post surgery | Will collect mortality data. |
| Radiological | 2 (+/- 1) days, 6 months (+/- 2 weeks) and 12 (+/- 1) months | Volumetric measurement of contrast enhancement on MRI |
| Safety using global disability | 6 months (+/- 2 weeks) and 12 (+/- 1) months post surgery | 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. |
| Efficacy using progression-free survival | 6 weeks (+/- 2 weeks), 6 months (+/- 2 weeks) and 12 (+/- 1) months post surgery | 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 |
| Feasibility using eligibility | Screening/Enrollment | Measures feasibility. Among all screened patients, the proportion of patients who meet the eligibility criteria |
| Feasibility using proportion of consent | Screening/Enrollment | Measures feasibility. Among all screened patients, the proportion of patients consenting to participate |
| Feasibility using number of completed visits | Through study completion, on average 2 years | Measures feasibility. Among all screened patients, the proportion of patients completing all scheduled follow-up assessments |
| Feasibility using Gross Total Resection | 2 days (+/- 1 day) post surgery | Measures feasibility. The proportion of radiographically-confirmed gross total resection of contrast-enhancing tumor based on the first MRI after surgery. |
| Efficacy using overall survival | 6 weeks (+/- 2 weeks), 6 months (+/- 2 weeks) and 12 (+/- 1) months post surgery | Measures efficacy. The date of death will be obtained from hospital records, outpatient follow up clinic notes, or provincial cancer registries. |
| Safety using quality of life | 6 months (+/- 2 weeks) and 12 (+/- 4 weeks) post surgery, 24 (+/- 4 weeks) post surgery | 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. |
| Safety using neurological function | 2 (+/- 1) days and 6 weeks (+/- 2 weeks), days post surgery | 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. |
Countries
Canada, United States
Contacts
PRINCIPAL_INVESTIGATORFarhad Pirouzmand, MD, MSc, FRCSC
Sunnybrook Health Sciences Centre
PRINCIPAL_INVESTIGATORAlireza Mansouri, MD MSc FRCSC
Penn State Cancer Institute
PRINCIPAL_INVESTIGATORDamon Scales, MD, PhD, FRCPC
Sunnybrook Health Sciences Centre
Outcome results
None listed