Clinical trial NCT04243005: Supramarginal Resection in Glioblastoma
Official title: Supramarginal Resection in Patients with Glioblastoma: a Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Glioblastoma
Keywords: Neurosurgical procedures
Lead sponsor: St. Olavs Hospital
Sponsor class: OTHER
Collaborators: name: Odense University Hospital
name: Sahlgrenska University Hospital
name: Turku University Hospital
name: Karolinska University Hospital
name: Norwegian University of Science and Technology
name: Uppsala University Hospital
name: University Hospital, Umeå
name: Haukeland University Hospital
name: Ullevaal University Hospital
name: Rikshospitalet University Hospital
name: Tampere University Hospital
name: Helsinki University Central Hospital
name: Kuopio University Hospital
name: Oulu University Hospital
name: Medical University of Vienna
name: Paracelsus Medical University
name: Medical Center Haaglanden, The Hague, The Netherlands
name: Erasmus Medical Center
First posted: 2020-01-27
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Overall survival
timeFrame: 36 months after the last included patient.
Secondary outcomes:
measure: Proportion alive
timeFrame: 24 months after randomization.
measure: Proportion alive
timeFrame: 36 months after randomization.
measure: Neurological function
timeFrame: Early postoperative (i.e. prior to radiotherapy) to 36 months
measure: Health-related quality of life assessed by EQ-5D 3L
timeFrame: Early postoperative (i.e. prior to radiotherapy) to 36 months
measure: Health-related quality of life assessed by EORTC QLQ C30
timeFrame: Early postoperative (i.e. prior to radiotherapy) to 36 months
measure: Health-related quality of life assessed by BN20
timeFrame: Early postoperative (i.e. prior to radiotherapy) to 36 months
measure: Neurocognition
timeFrame: Early postoperative (i.e. prior to radiotherapy) to 36 months
measure: Surgical complication
timeFrame: 30 days
measure: Proportion with contrast remnant
timeFrame: Within 72 hours postoperative
measure: Extent of resection, T2/FLAIR remnant
timeFrame: Within 72 hours postoperative
measure: Margin of resection
timeFrame: Within 72 hours postoperative
Other outcomes:
measure: Overall Survival; as treated
timeFrame: 36 months after the last included patient.
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Odense
country: Denmark
facility: Odense University Hospital
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Kuopio
country: Finland
facility: Kuopio University Hospital
city: Oulu
country: Finland
facility: Oulu University Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Turku
country: Finland
facility: Turku University Hospital
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: The Hague
country: Netherlands
facility: Haaglanden MC
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Oslo
country: Norway
facility: Oslo University Hospital, Rikshospitalet
city: Oslo
country: Norway
facility: Ullevål University Hospital
city: Trondheim
country: Norway
facility: St Olavs Hospital
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital,
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Umeå
country: Sweden
facility: University Hospital of Umeå
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
Study officials:
affiliation: St.Olavs University Hospital and Sahlgrenska University Hospital
name: Asgeir S Jakola, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Olavs Hospital
name: Geir Bråthen, MD, PhD
role: STUDY_DIRECTOR
References: