To investigate if resection with a margin, that is significantly beyond the radiological contrast enhancement, improves overall survival in selected patients with glioblastoma.
ID
Source
Brief title
Condition
- Nervous system neoplasms malignant and unspecified NEC
- Nervous system, skull and spine therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study endpoint is overall survival according to intention-to-treat
principle 36 months after the last included and randomized patient.
Secondary outcome
• Investigate survival 24 and 36 months after randomization.
• Investigate the neurological function using the Neurological assessment in
Neuro-Oncology (NANO) at early postoperative control and at study closure.
• Determine health-related quality of life using EQ-5D 3L, EORTC QLQ C30 and
BN20 questionnaires.
• Determine Neurocognition according to Mini Mental Status Examination (MMSE).
• Investigate perioperative 30 day surgical complications grade 3, 4 and 5,
assessed using the Dindo-Clavien classification.
• Determine the extent of resection using unintended contrast remnant, T2/FLAIR
remnant and Cavity volume/contrast enhancement volume data
Background summary
Gliomas are the most common malignant brain tumor, and they result in more
years of life lost than any other tumor group. 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. We think there is significant potential in
individualized surgical decision-making in glioblastoma management, as it is
counterintuitive that one size fits all. The current concept in all patients
with glioblastoma is *maximum safe resection of the contrast enhancing tumor*,
but we think this may be extended to simply *maximum safe resection* tailored
to the patient and extent of disease at hand. The BOLD trial will therefor
investigate if resection with a margin, that is significantly beyond the
radiological contrast enhancement, improves survival in selected patients with
glioblastoma.
Study objective
To investigate if resection with a margin, that is significantly beyond the
radiological contrast enhancement, improves overall survival in selected
patients with glioblastoma.
Study design
This is a multicenter randomized controlled trial with parallel group design in
newly diagnosed suspected glioblastoma amendable to supramarginal resection.
Patients will be randomized 1:1 between surgical removal of tissue clearly
beyond the contrast enhancement seen on magnetic resonance imaging
(supramarginal surgery group) and surgical removal of the tissue corresponding
to the contrast enhancement on MRI (conventional surgery group).
Intervention
Surgical removal of tissue clearly beyond the contrast enhancement seen on
magnetic resonance imaging (supramarginal surgery).
Study burden and risks
Patients with glioblastoma have a very poor prognosis. Surgery is often the
only way to remove most of the tumor. A supramarginal resection has almost the
same risk of complications as a normal resection, while the chance of longer
survival appears to be greater because more of the tumor can be removed. The
additional questionnaires and cognitive examinations are a very minor burden
for the patients.
This research can contribute to improving treatment for patients with GBM and
therefore ensure longer survival with a better quality of life.
Olav Kyrres gate 17
Trondheim 7030
NO
Olav Kyrres gate 17
Trondheim 7030
NO
Listed location countries
Age
Inclusion criteria
The subjects must fulfill all the following inclusion criteria to be eligible
for participation in the study, unless otherwise specified:
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. Age 18 years or older.
5. Karnofsky performance status of 70 - 100.41
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
Potential study subjects who meet any of the following criteria are not
eligible for participation in the study:
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
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT04243005 |
| CCMO | NL86360.078.24 |