Glioma Supra Marginal Incision Trial (G-SUMIT)

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

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?

Study Overview

• Status: Recruiting
• Conditions: High Grade Glioma
• Intervention / Treatment: Procedure: Supramarginal resection; Procedure: Conventional (i.e. GTR) resection

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.

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ainy Zahid, HBSc.; Phone Number: 416-480-5631; Email: ainy.zahid@sunnybrook.ca
• Study Contact Backup: Name: Farhad Pirouzmand, MD, MSc, FRCSC; Phone Number: 5263 416-480-6100; Email: farhad.pirouzmand@sunnybrook.ca

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Recruiting
      • Mackenzie Health Sciences Center
      • Contact: Mathew Mossey; Email: mmossey@ualberta.ca
      • Principal Investigator: Cian OKelly, MD
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
      • Recruiting
      • Kingston Health Sciences Centre
      • Contact: Craig Spencer; Email: craig.spencer@kingstonhsc.ca
      • Principal Investigator: Teresa Purzner, MD
    • Toronto, Ontario, Canada
      • Recruiting
      • Sunnybrook Health Sciences Centre
      • Contact: Farhad Pirouzmand, MD, MSc, FRCSC; Phone Number: 5263 416-480-6100; Email: farhad.pirouzmand@sunnybrook.ca
    • Toronto, Ontario, Canada, M5B 1W8
      • Recruiting
      • St Michael's Hospital
      • Contact: Clementine k Affana; Email: Clementine.KoaAffana@unityhealth.to
      • Principal Investigator: Sunit Das, MD
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada
      • Recruiting
      • University of Saskatchewan
      • Principal Investigator: Michael Kelly, MD
      • Contact: Jessica Grosskleg; Phone Number: jessica.grosskleg@usask.ca
• United States
  • Pennsylvania
    • University Park, Pennsylvania, United States, 16802
      • Recruiting
      • The Pennsylvania State University
      • Contact: Ann Needles, BSc; Phone Number: 283114 717-531-0003; Email: aneedles@pennstatehealth.psu.edu
      • Principal Investigator: Seyed A Manouri, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Supramarginal resection (intervention arm); 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; 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.
Other: Conventional (i.e. GTR) resection; Planned resection of ≥95% of the GAD-enhancing regions of tumor without expanding the resection beyond this margin.	Procedure: Conventional (i.e. GTR) resection; Planned resection of ≥95% of the GAD-enhancing regions of tumor without expanding the resection beyond this margin.

What is the study measuring?

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
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
Radiological	Volumetric measurement of contrast enhancement on MRI	2 (+/- 1) days, 6 months (+/- 2 weeks) and 12 (+/- 1) months
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 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

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Collaborators: Canadian Institutes of Health Research (CIHR); Sunnybrook Research Institute
• Investigators: Principal Investigator: Alireza Mansouri, MD MSc FRCSC, Penn State Cancer Institute; Principal Investigator: Farhad Pirouzmand, MD, MSc, FRCSC, Sunnybrook Health Sciences Centre; Principal Investigator: Damon Scales, MD, PhD, FRCPC, Sunnybrook Health Sciences Centre

Publications and helpful links

General Publications

• Mansouri A, Lai C, Scales D, Pirouzmand F. A phase II pilot randomized controlled trial to assess the feasibility of the "supra-marginal" surgical resection of malignant glioma (G-SUMIT: Glioma supra marginal incision trial) study protocol. Pilot Feasibility Stud. 2022 Jul 5;8(1):138. doi: 10.1186/s40814-022-01104-1.

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2021
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: January 19, 2021
• First Submitted That Met QC Criteria: February 1, 2021
• First Posted (Actual): February 4, 2021

Study Record Updates

• Last Update Posted (Estimated): June 16, 2023
• Last Update Submitted That Met QC Criteria: June 15, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Surgery; HGG; Brain tumor; Supramarginal resection; Standard total resection
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma
• Other Study ID Numbers: CTO 3297

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No