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Glioma Supra Marginal Incision Trial

Not Applicable
Recruiting
Conditions
High Grade Glioma
Interventions
Procedure: Supramarginal resection
Procedure: Conventional (i.e. GTR) resection
Registration Number
NCT04737577
Lead Sponsor
Sunnybrook Health Sciences Centre
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
72
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Supramarginal resection (intervention arm)Supramarginal resectionPlanned 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.
Conventional (i.e. GTR) resectionConventional (i.e. GTR) resectionPlanned resection of ≥95% of the GAD-enhancing regions of tumor without expanding the resection beyond this margin.
Primary Outcome Measures
NameTimeMethod
EnrollmentCollected 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 Outcome Measures
NameTimeMethod
Feasibility using Gross Total Resection2 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.

Feasibility using proportion of consentScreening/Enrollment

Measures feasibility. Among all screened patients, the proportion of patients consenting to participate

Efficacy using progression-free survival6 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

Safety using global disability6 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.

Feasibility using number of completed visitsThrough study completion, on average 2 years

Measures feasibility. Among all screened patients, the proportion of patients completing all scheduled follow-up assessments

Safety using neurological function2 (+/- 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.

Safety using 6 weeks (+/- 2 weeks) all cause-mortality6 weeks (+/- 2 weeks) post surgery

Will collect mortality data.

Radiological2 (+/- 1) days, 6 months (+/- 2 weeks) and 12 (+/- 1) months

Volumetric measurement of contrast enhancement on MRI

Feasibility using eligibilityScreening/Enrollment

Measures feasibility. Among all screened patients, the proportion of patients who meet the eligibility criteria

Efficacy using overall survival6 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 life6 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.

Trial Locations

Locations (6)

University of Saskatchewan

🇨🇦

Saskatoon, Saskatchewan, Canada

The Pennsylvania State University

🇺🇸

University Park, Pennsylvania, United States

St Michael's Hospital

🇨🇦

Toronto, Ontario, Canada

Kingston Health Sciences Centre

🇨🇦

Kingston, Ontario, Canada

Mackenzie Health Sciences Center

🇨🇦

Edmonton, Alberta, Canada

Sunnybrook Health Sciences Centre

🇨🇦

Toronto, Ontario, Canada

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