Supramarginal Resection in Glioblastoma

December 14, 2023 updated by: St. Olavs Hospital

Supramarginal Resection in Patients With Glioblastoma: A Randomised Controlled Trial

Gliomas are the most common malignant brain tumor. Glioblastoma, WHO grade IV astrocytoma, is the most common subtype and unfortunately also the most aggressive subtype with median survival in population based cohorts being only 10 months. Extensive surgical resections followed by postoperative fractioned radiotherapy and concomitant and adjuvant temozolomide prolong survival and is the standard treatment.

The investigators think there is significant potential in individualized surgical decision-making in glioblastoma management. The idea that some patients are amendable to radical surgery, while others should be treated more conservatively, is not controversial in other fields of oncology. The current concept in all patients with glioblastoma is "maximum safe resection of the contrast enhancing tumor", but this may in selected cases be extended to simply "maximum safe resection" tailored to the patient and extent of disease at hand.

Densely proliferating tumor cells have been found from at an average of 10 mm beyond the margins of contrast enhancement in high-grade gliomas. There are now several case series, using various definitions of supramarginal resection, but they have in common that they report a benefit of resection with a margin. This potential benefit also comes together with an associated neurological risk, making this approach unethical and simply not feasible in the patients with glioblastoma as a whole.

Objective of this study is: To investigate if resection with a margin, that is significantly beyond the radiological contrast enhancement, improves survival in selected patients with glioblastoma.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

90

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. A suspected diagnosis of supratentorial glioblastoma by MRI.(A)
  2. Indication for surgical treatment and where supramarginal resection is considered possible according to the preoperative imaging. This consideration needs to be verified by two specialists in neurosurgery.
  3. Negative work-up for other primary tumor(B)
  4. Karnofsky performance status of 70 - 100.

A) If randomized to supramarginal surgery, intraoperative frozen section must conclude with "high-grade glioma" to be able to proceed. Surgery in two sessions is also possible in supramarginal group if there is no intraoperative frozen section available or frozen section indicate another diagnosis, but final histopathology reveals a glioblastoma. In case of surgery in two session, there must be no more than 30 days between procedures. See flow-chart in attachment 1.

B) No suspected primary tumor seen on CT chest, abdomen and pelvis. If relevant symptoms/clinical suspicion also supplement with mammography, dermatologist exam, relevant endoscopies etc.

Exclusion Criteria:

  1. Not willing to be randomized.
  2. Informed consent not possible (e.g. language barriers, aphasia, cognitive severely impaired).
  3. Contrast enhancement volume bilateral OR involving corpus callosum.
  4. Contrast enhancement along the ependymal lining of ventricles (contact is however not an exclusion criteria).
  5. Contrast enhancement involving several lobes.
  6. History of major psychiatric disorder such as psychosis, schizophrenia and/or mood disorder (e.g. depression and bipolar disorder) in need of hospitalization
  7. Unfit for participation for any other reason judged by the including physician

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Conventional surgery
Aim of gross total resection (i.e. removal of contrast enhancing tumor) according to institutional practice. No limit in use of technical adjuncts in this arm.
Procedure: Conventional surgery
Aim of gross total resection (i.e. removal of contrast enhancing tumor) according to institutional practice. No limit in use of technical adjuncts in this arm.
Experimental: Supramarginal surgery
Aim of supramarginal resection, where a margin of at least 10 mm is considered feasible prior to surgery. The resection is guided by the T2 volume (i.e. zone of edema) where removal of as much as possible of this zone (or beyond) is attempted as long as considered safe
Procedure: Supramarginal resection
Aim of supramarginal resection, where a margin of at least 10 mm is considered feasible prior to surgery. The resection is guided by the T2 volume (i.e. zone of edema) where removal of as much as possible of this zone (or beyond) is attempted as long as considered safe

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 36 months after the last included patient.
Overall survival according to intention-to-treat
36 months after the last included patient.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion alive
Time Frame: 24 months after randomization.
Proportion alive
24 months after randomization.
Proportion alive
Time Frame: 36 months after randomization.
Proportion alive
36 months after randomization.
Neurological function
Time Frame: Early postoperative (i.e. prior to radiotherapy) to 36 months
Neurological assessment in Neuro-Oncology (NANO) Scale is a tool used by healthcare providers to objectively quantify the impairment caused by a tumor within the central nervous system. The NANO is composed of 9 items. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NANO scale score. The maximum possible score is 23, with the minimum score being a 0.
Early postoperative (i.e. prior to radiotherapy) to 36 months
Health-related quality of life assessed by EQ-5D 3L
Time Frame: Early postoperative (i.e. prior to radiotherapy) to 36 months
The EQ-5D-3L descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results into a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.
Early postoperative (i.e. prior to radiotherapy) to 36 months
Health-related quality of life assessed by EORTC QLQ C30
Time Frame: Early postoperative (i.e. prior to radiotherapy) to 36 months
The QLQ-C30 is a cancer health-related quality-of-life questionnaire that has been widely used in clinical trials and investigations using PROs for individual patient management. It includes five function domains (physical, emotional, social, role, cognitive), eight symptoms (fatigue, pain, nausea/vomiting, constipation, diarrhea, insomnia, dyspnea, and appetite loss), as well as global health/quality-of-life and financial impact. Subjects respond on a four-point scale from "not at all" to "very much" for most items. Most items use a "past week" recall period. Raw scores are linearly converted to a 0-100 scale with higher scores reflecting higher levels of function and higher levels of symptom burden.
Early postoperative (i.e. prior to radiotherapy) to 36 months
Health-related quality of life assessed by BN20
Time Frame: Early postoperative (i.e. prior to radiotherapy) to 36 months
The European Organization for Research and Treatment of Cancer (EORTC) QLQ-BN20 is a quality of life assessment specific to brain neoplasms. Consists of 20 items that assess future uncertainty, visual disorder, motor dysfunction, and communication deficit. Items are presented as questions on a scale ranging from 1 = "not at all" to 4 = "very much." Higher score means worse outcome.
Early postoperative (i.e. prior to radiotherapy) to 36 months
Neurocognition
Time Frame: Early postoperative (i.e. prior to radiotherapy) to 36 months
The Mini-Mental State Examination (MMSE) or Folstein test is a 30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment. It examines functions including registration (repeating named prompts), attention and calculation, recall, language, ability to follow simple commands and orientation. Any score of 24 or more (out of 30) indicates a normal cognition. Below this, scores can indicate severe (≤9 points), moderate (10-18 points) or mild (19-23 points) cognitive impairment.
Early postoperative (i.e. prior to radiotherapy) to 36 months
Surgical complication
Time Frame: 30 days
surgical complication grade 3, 4 and 5, assessed using the Dindo-Clavien classification
30 days
Proportion with contrast remnant
Time Frame: Within 72 hours postoperative
Resection proportion with contrast remnant
Within 72 hours postoperative
Extent of resection, T2/FLAIR remnant
Time Frame: Within 72 hours postoperative
Proportion with remnant in terms of hyper intensity changes in T2/FLAIR
Within 72 hours postoperative
Margin of resection
Time Frame: Within 72 hours postoperative
Cavity volume/contrast enhancement volume
Within 72 hours postoperative

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival; as treated
Time Frame: 36 months after the last included patient.
Accounting for cross-over or failure to achieve predefined surgical aim. "As treated" populations when no margins in supramarginal group and unintended contrast remnant in group aiming at conventional gross-total resection or even if significant supramarginal resection in this group
36 months after the last included patient.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

St. Olavs Hospital

Collaborators

Odense University Hospital
Karolinska University Hospital
Turku University Hospital
Ullevaal University Hospital
Medical University of Vienna
Helsinki University Central Hospital
Oulu University Hospital
Kuopio University Hospital
University Hospital of North Norway
Norwegian University of Science and Technology
Sahlgrenska University Hospital, Sweden
Haukeland University Hospital
Rikshospitalet University Hospital
University Hospital, Linkoeping
Tampere University Hospital
Skane University Hospital
University Hospital, Umeå
Paracelsus Medical University
Uppsala University Hospital

Investigators

  • Principal Investigator: Asgeir S Jakola, MD, PhD, St.Olavs University Hospital and Sahlgrenska University Hospital
  • Study Director: Geir Bråthen, MD, PhD, St. Olavs Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2020

Primary Completion (Estimated)

March 1, 2026

Study Completion (Estimated)

March 1, 2030

Study Registration Dates

First Submitted

January 8, 2020

First Submitted That Met QC Criteria

January 24, 2020

First Posted (Actual)

January 27, 2020

Study Record Updates

Last Update Posted (Estimated)

December 15, 2023

Last Update Submitted That Met QC Criteria

December 14, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2019/1046

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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