Back to resultsSupramarginal Resection in Glioblastoma
Primary Purpose
Glioblastoma
Status
Recruiting
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Supramarginal resection
Conventional surgery
Sponsored by
About this trial
This is an interventional treatment trial for Glioblastoma focused on measuring Neurosurgical procedures
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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 along the ependymal lining of ventricles (contact is however not an exclusion criteria).
- 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
Sites / Locations
- Medical University of ViennaRecruiting
- Odense University HospitalRecruiting
- Helsinki University HospitalRecruiting
- Kuopio University HospitalRecruiting
- Oulu University HospitalRecruiting
- Tampere University HospitalRecruiting
- Turku University HospitalRecruiting
- Haukeland University HospitalRecruiting
- Oslo University Hospital, RikshospitaletRecruiting
- Ullevål University HospitalRecruiting
- University Hospital North NorwayRecruiting
- St Olavs HospitalRecruiting
- Sahlgrenska University Hospital,Recruiting
- Linköping University HospitalRecruiting
- Skåne University HospitalRecruiting
- Karolinska University HospitalRecruiting
- University Hospital of UmeåRecruiting
- Uppsala University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Conventional surgery
Supramarginal surgery
Arm Description
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.
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
Outcomes
Primary Outcome Measures
Overall survival
Overall survival according to intention-to-treat
Secondary Outcome Measures
Proportion alive
Proportion alive
Proportion alive
Proportion alive
Neurological function
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.
Health-related quality of life assessed by EQ-5D 3L
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.
Health-related quality of life assessed by EORTC QLQ C30
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.
Health-related quality of life assessed by BN20
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.
Neurocognition
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.
Surgical complication
surgical complication grade 3, 4 and 5, assessed using the Dindo-Clavien classification
Proportion with contrast remnant
Resection proportion with contrast remnant
Extent of resection, T2/FLAIR remnant
Proportion with remnant in terms of hyper intensity changes in T2/FLAIR
Margin of resection
Cavity volume/contrast enhancement volume
Full Information
NCT ID
NCT04243005
First Posted
January 8, 2020
Last Updated
December 7, 2022
Sponsor
St. Olavs Hospital
Collaborators
Odense University Hospital, Sahlgrenska University Hospital, Sweden, Turku University Hospital, Karolinska University Hospital, Norwegian University of Science and Technology, University Hospital, Linkoeping, Uppsala University Hospital, University Hospital, Umeå, Skane University Hospital, Haukeland University Hospital, Ullevaal University Hospital, Rikshospitalet University Hospital, University Hospital of North Norway, Tampere University Hospital, Helsinki University Central Hospital, Kuopio University Hospital, Oulu University Hospital, Medical University of Vienna, Paracelsus Medical University
1. Study Identification
Unique Protocol Identification Number
NCT04243005
Brief Title
Supramarginal Resection in Glioblastoma
Official Title
Supramarginal Resection in Patients With Glioblastoma: A Randomised Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2020 (Actual)
Primary Completion Date
March 2026 (Anticipated)
Study Completion Date
March 2030 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
St. Olavs Hospital
Collaborators
Odense University Hospital, Sahlgrenska University Hospital, Sweden, Turku University Hospital, Karolinska University Hospital, Norwegian University of Science and Technology, University Hospital, Linkoeping, Uppsala University Hospital, University Hospital, Umeå, Skane University Hospital, Haukeland University Hospital, Ullevaal University Hospital, Rikshospitalet University Hospital, University Hospital of North Norway, Tampere University Hospital, Helsinki University Central Hospital, Kuopio University Hospital, Oulu University Hospital, Medical University of Vienna, Paracelsus Medical University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma
Keywords
Neurosurgical procedures
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Masking Description
Participants will be masked until postoperative period. Outcome assessor will be masked until all predefined outcomes have been analysed
Allocation
Randomized
Enrollment
90 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Conventional surgery
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Supramarginal surgery
Arm Type
Experimental
Arm Description
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
Intervention Type
Procedure
Intervention Name(s)
Supramarginal resection
Intervention Description
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
Intervention Type
Procedure
Intervention Name(s)
Conventional surgery
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall survival
Description
Overall survival according to intention-to-treat
Time Frame
36 months after the last included patient.
Secondary Outcome Measure Information:
Title
Proportion alive
Description
Proportion alive
Time Frame
24 months after randomization.
Title
Proportion alive
Description
Proportion alive
Time Frame
36 months after randomization.
Title
Neurological function
Description
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.
Time Frame
Early postoperative (i.e. prior to radiotherapy) to 36 months
Title
Health-related quality of life assessed by EQ-5D 3L
Description
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.
Time Frame
Early postoperative (i.e. prior to radiotherapy) to 36 months
Title
Health-related quality of life assessed by EORTC QLQ C30
Description
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.
Time Frame
Early postoperative (i.e. prior to radiotherapy) to 36 months
Title
Health-related quality of life assessed by BN20
Description
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.
Time Frame
Early postoperative (i.e. prior to radiotherapy) to 36 months
Title
Neurocognition
Description
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.
Time Frame
Early postoperative (i.e. prior to radiotherapy) to 36 months
Title
Surgical complication
Description
surgical complication grade 3, 4 and 5, assessed using the Dindo-Clavien classification
Time Frame
30 days
Title
Proportion with contrast remnant
Description
Resection proportion with contrast remnant
Time Frame
Within 72 hours postoperative
Title
Extent of resection, T2/FLAIR remnant
Description
Proportion with remnant in terms of hyper intensity changes in T2/FLAIR
Time Frame
Within 72 hours postoperative
Title
Margin of resection
Description
Cavity volume/contrast enhancement volume
Time Frame
Within 72 hours postoperative
Other Pre-specified Outcome Measures:
Title
Overall Survival; as treated
Description
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
Time Frame
36 months after the last included patient.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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 along the ependymal lining of ventricles (contact is however not an exclusion criteria).
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Asgeir S Jakola, MD, PhD
Phone
+47 72 57 30 00
Email
legepost@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Sasha Gulati, MD, PhD
Phone
+47 72 57 30 00
Email
sasha.gulati@ntnu.no
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Asgeir S Jakola, MD, PhD
Organizational Affiliation
St.Olavs University Hospital and Sahlgrenska University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Geir Bråthen, MD, PhD
Organizational Affiliation
St. Olavs Hospital
Official's Role
Study Director
Facility Information:
Facility Name
Medical University of Vienna
City
Vienna
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Georg Widhalm
Email
georg.widhalm@meduniwien.ac.at
Facility Name
Odense University Hospital
City
Odense
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Frants R Poulsen
Email
frantz.r.poulsen@rsyd.dk
First Name & Middle Initial & Last Name & Degree
Christian Bonde Pedersen
Email
Christian.bonde@rsyd.dk
Facility Name
Helsinki University Hospital
City
Helsinki
Country
Finland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jarno Satopää
Email
jarno.satopaa@hus.fi
First Name & Middle Initial & Last Name & Degree
Justiina Huhtakangas
Email
justiina.huhtakangas@hus.fi
Facility Name
Kuopio University Hospital
City
Kuopio
Country
Finland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olli-Pekka Kämäräinen
Email
olli-pekka.kamarainen@kuh.fi
Facility Name
Oulu University Hospital
City
Oulu
Country
Finland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sami Tetri
Email
sami.tetri@ppshp.fi
Facility Name
Tampere University Hospital
City
Tampere
Country
Finland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joonas Haapasalo
Email
joonas.haapasalo@gmail.com
Facility Name
Turku University Hospital
City
Turku
Country
Finland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ville Vuorinen
Email
ville.vuorinen@tyks.fi
First Name & Middle Initial & Last Name & Degree
Jussi Posti
Email
jussi.posti@utu.fi
Facility Name
Haukeland University Hospital
City
Bergen
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ruby Mahesperan
Email
rupavathana.mahesparan@helse-bergen.no
Facility Name
Oslo University Hospital, Rikshospitalet
City
Oslo
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Einar Vik-Mo
Email
e.o.vik-mo@medisin.uio.no
Facility Name
Ullevål University Hospital
City
Oslo
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eirik Helseth
Email
EHELSETH@ous-hf.no
Facility Name
University Hospital North Norway
City
Tromsø
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Roar Kloster
Email
roar.kloster@unn.no
Facility Name
St Olavs Hospital
City
Trondheim
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ole Solheim
Email
ole.solheim@ntnu.no
First Name & Middle Initial & Last Name & Degree
Sasha Gulati
Email
sasha.gulati@ntnu.no
Facility Name
Sahlgrenska University Hospital,
City
Göteborg
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Asgeir S Jakola
Email
legepost@gmail.com
First Name & Middle Initial & Last Name & Degree
Louise Carstam
Email
louise.carstam@vgregion.se
Facility Name
Linköping University Hospital
City
Linköping
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter Milos
Email
Peter.milos@regionostergotland.se
Facility Name
Skåne University Hospital
City
Lund
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gregor Tomasevic
Email
gregor.tomasevic@med.lu.se
Facility Name
Karolinska University Hospital
City
Stockholm
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Margret Jensdottir
Email
margret.jensdottir@sll.se
First Name & Middle Initial & Last Name & Degree
Jiri Bartek jr
Email
jiri.bartek@sll.se
Facility Name
University Hospital of Umeå
City
Umeå
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rickard Sjöberg
Email
Rickard.Sjoberg@vll.se
Facility Name
Uppsala University Hospital
City
Uppsala
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mats Ryttlefors
Email
mats.ryttlefors@neuro.uu.se
12. IPD Sharing Statement
Plan to Share IPD
No
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Supramarginal Resection in Glioblastoma
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