NCT04243005

Brief Summary

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.

Trial Health

82
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
90

participants targeted

Target at P50-P75 for not_applicable

Timeline
54mo left

Started Jul 2020

Longer than P75 for not_applicable

Geographic Reach
6 countries

17 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress57%
Jul 2020Dec 2030

First Submitted

Initial submission to the registry

January 8, 2020

Completed
19 days until next milestone

First Posted

Study publicly available on registry

January 27, 2020

Completed
5 months until next milestone

Study Start

First participant enrolled

July 1, 2020

Completed
7.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2027

Expected
3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2030

Last Updated

March 3, 2026

Status Verified

February 1, 2026

Enrollment Period

7.4 years

First QC Date

January 8, 2020

Last Update Submit

March 2, 2026

Conditions

Glioblastoma

Keywords

Neurosurgical procedures

Outcome Measures

Primary Outcomes (1)

  • Overall survival

    Overall survival according to intention-to-treat

    36 months after the last included patient.

Secondary Outcomes (11)

  • Proportion alive

    24 months after randomization.

  • Proportion alive

    36 months after randomization.

  • Neurological function

    Early postoperative (i.e. prior to radiotherapy) to 36 months

  • Health-related quality of life assessed by EQ-5D 3L

    Early postoperative (i.e. prior to radiotherapy) to 36 months

  • Health-related quality of life assessed by EORTC QLQ C30

    Early postoperative (i.e. prior to radiotherapy) to 36 months

  • +6 more secondary outcomes

Other Outcomes (1)

  • Overall Survival; as treated

    36 months after the last included patient.

Study Arms (2)

Conventional surgery

ACTIVE COMPARATOR

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

Supramarginal surgery

EXPERIMENTAL

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

Interventions

Conventional surgeryPROCEDURE

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.

Conventional surgery
Supramarginal resectionPROCEDURE

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

Supramarginal surgery

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • A suspected diagnosis of supratentorial glioblastoma by MRI.(A)
  • 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.
  • Negative work-up for other primary tumor(B)
  • 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.

You may not qualify if:

  • Not willing to be randomized.
  • Informed consent not possible (e.g. language barriers, aphasia, cognitive severely impaired).
  • Contrast enhancement volume bilateral OR involving corpus callosum.
  • Contrast enhancement involving several lobes.
  • History of major psychiatric disorder such as psychosis, schizophrenia and/or mood disorder (e.g. depression and bipolar disorder) in need of hospitalization
  • Unfit for participation for any other reason judged by the including physician

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (17)

Medical University of Vienna

Vienna, Austria

Location

Odense University Hospital

Odense, Denmark

Location

Helsinki University Hospital

Helsinki, Finland

Location

Kuopio University Hospital

Kuopio, Finland

Location

Oulu University Hospital

Oulu, Finland

Location

Tampere University Hospital

Tampere, Finland

Location

Turku University Hospital

Turku, Finland

Location

Erasmus MC

Rotterdam, Netherlands

Location

Haaglanden MC

The Hague, Netherlands

Location

Haukeland University Hospital

Bergen, Norway

Location

Oslo University Hospital, Rikshospitalet

Oslo, Norway

Location

Ullevål University Hospital

Oslo, Norway

Location

St Olavs Hospital

Trondheim, Norway

Location

Sahlgrenska University Hospital,

Gothenburg, Sweden

Location

Karolinska University Hospital

Stockholm, Sweden

Location

University Hospital of Umeå

Umeå, Sweden

Location

Uppsala University Hospital

Uppsala, Sweden

Location

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

AstrocytomaGliomaNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve Tissue

Study Officials

  • Asgeir S Jakola, MD, PhD

    St.Olavs University Hospital and Sahlgrenska University Hospital

    PRINCIPAL INVESTIGATOR

  • Geir Bråthen, MD, PhD

    St. Olavs Hospital

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Masking Details
Participants will be masked until postoperative period. Outcome assessor will be masked until all predefined outcomes have been analysed
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 8, 2020

First Posted

January 27, 2020

Study Start

July 1, 2020

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2030

Last Updated

March 3, 2026

Record last verified: 2026-02

Data Sharing

IPD Sharing
Will not share

Locations

SE(4)AU(1)DK(1)NL(2)NO(4)FI(5)