The SAFE-Trial: Awake Craniotomy Versus Surgery Under General Anesthesia for Glioblastoma Patients. (SAFE)
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|ClinicalTrials.gov Identifier: NCT03861299|
Recruitment Status : Recruiting
First Posted : March 4, 2019
Last Update Posted : October 27, 2020
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma Glioblastoma Multiforme Glioblastoma Multiforme of Brain Astrocytoma, Grade IV Brain Tumor Brain Cancer Brain Neoplasms||Procedure: Awake craniotomy Procedure: Craniotomy under general anesthesia||Not Applicable|
Rationale Glioblastoma Multiforme (GBM) or Astrocytoma's grade IV (WHO) are devastating tumors with one of the worst prognoses in oncology. Extending resection improves survival in patients with GBM. Surgery of GBM nowadays is usually performed under general anesthesia (GA) and resections are not as aggressive as possible, due to the chance of seriously damaging the patient with a rather low life expectancy. A surgical technique optimizing resection of the tumor in eloquent areas but preventing neurological deficits is necessary to improve survival and quality of life in these patients. Awake craniotomy (AC) with the use of cortical and subcortical stimulation is an alternative surgical technique that is standardly implemented in surgery for low grade glioma, but not yet for GBM. AC has shown to increase resection percentage and preserve quality of life in low grade glioma (LGG) and could be of important value in the surgery of GBM.
Objective The study is performed to increase safety and efficacy during surgery in patients with GBM in eloquent areas. This study will compare awake craniotomy with surgery under general anesthesia for patients with GBM near or in eloquent areas. Primary end points are: 1) Proportion of patients with NIH Stroke Scale (NIHSS) deterioration at 6 weeks post- surgery, where deterioration is defined as at least one point increase in total NIHSS score compared to baseline. 2) Proportion of patients without residual contrast-enhancing tumour on postoperative MRI. Secondary end points are: 1) Health related quality of life (HRQoL) at 6 weeks, 3 months and 6 months after operation. 2) Progression-free survival (PFS) at 12 months after operation. 3) Overall survival (OS) at 12 months after operation. 4) Frequency and severity of Serious Adverse Effects in each group: Infections, intracranial bleeding, epilepsy, aphasia, paresis/paralysis in arms or/and legs. Also, a cost benefit analysis will be performed.
Study design The trial is set up as a multicenter randomized controlled study. The study will include 246 patients in 5 neurosurgical centers in the Netherlands. Patients with GBM in eloquent areas on diagnostic MRI will be selected by the neurosurgeons according to the eligibility criteria. After informed consent the patient will be randomized for awake craniotomy (AC) or regular craniotomy under general anesthesia (GA) with 1:1 allocation ratio. After surgery, only patients with histologically proven GBM will continue with the study. Patients in whom no GBM could not be proven histologically, will be considered off-study. Thereafter, patients will receive the standard treatment with concomitant Temozolomide and radiation therapy and standard follow up. Total duration of the study is 5 years. Patient inclusion is 4 years. Follow-up is 1 year.
Study population Patients aged 18-90 years old, with Glioblastoma Multiforme near or in eloquent areas and eligible for awake craniotomy.
Intervention Awake craniotomy compared to craniotomy under general anaesthesia
Main study parameters/endpoints
- Proportion of patients with NIHSS deterioration at 6 weeks post-surgery
- Proportion of patients without residual contrast-enhancing tumour on postoperative MRI
Nature and extent of the burden and risks associated with participation, benefit and group relatedness Patients have 50% chance to be randomized for an awake procedure. The risk-benefit-ratio of this procedure in patients with GBM is subject of this trial and the investigators expect less neurological morbidity than surgery under generalised anaesthesia. Three quality of life questionnaires and 1 neurological examination will take place preoperatively, 6 weeks after, 3 months after and 6 months after the surgery. The burden of this trial for the patient is therefore confined.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||246 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Each participating center will randomise eligible and willing patients through the webbased clinical database and randomisation application ALEA. The Clinical Trial Centre (CTC) of the Erasmus MC will build the randomisation application by use of a dynamic allocation algorithm (minimization), in which patients are allocated to keep the imbalance between treatment groups to a minimum at every stage of recruitment within the covariates age (≤55 years vs >55years), Karnofsky performance scale (80-90 vs >90), and left or right hemisphere. Treatment allocation and allocated subject number will be shown immediately on screen and will in addition automatically be emailed to local investigators and other study personnel|
|Masking:||None (Open Label)|
|Official Title:||The SAFE-Trial: Safe Surgery for Glioblastoma Multiforme: Awake Craniotomy Versus Surgery Under General Anesthesia. A Multicenter Prospective Randomised Controlled Study|
|Actual Study Start Date :||April 1, 2019|
|Estimated Primary Completion Date :||April 1, 2023|
|Estimated Study Completion Date :||April 1, 2024|
Experimental: Awake craniotomy
Cortical stimulation is performed with a bipolar electrical stimulator. The Boston naming test and repetition of words is done in cooperation with a neuropsychologist/linguist, who will inform the neurosurgeon of any kind of speech arrest or dysarthria. When localizing the motor and sensory cortex, the patient is asked to report any unintended movement or sensation in extremities or face. Functional cortical areas are marked with a number. When the tumour margins or white matter is encountered or when on regular neuronavigation the eloquent white matter tracts are thought to be in close proximity, subcortical stimulation (biphasic currents of 8-16 mA, pulse frequency 60 Hz, single pulse phase duration of 100 microsec., 2-second train) is performed to localize functional tracts.
Procedure: Awake craniotomy
Active Comparator: Craniotomy under general anesthesia
Trephination and tumour resection are performed without any additional neuro-psychological monitoring or brain mapping, guided by STEALTH-neuronavigation.
Procedure: Craniotomy under general anesthesia
Craniotomy under general anesthesia
- Postoperative neurological morbidity [ Time Frame: Between operation and 6 weeks postoperatively ]Proportion of patients with NIHSS (National Institute of Health Stroke Scale) deterioration at 6 weeks post-surgery, where deterioration is defined as at least one point increase in total NIHSS score compared to baseline
- Proportion of gross-total resections [ Time Frame: Assessed on 48 hours postoperative scan ]Proportion of patients without residual contrast-enhancing tumour on postoperative MRI, where residual tumour is defined as contrast-enhancement with a volume more than 0.175 cm3.
- Health-related quality of life assessed by EQ-5D questionnaire [ Time Frame: Between baseline and 6 weeks/3 months/6 months postoperatively ]Health related quality of life (HRQoL) at 6 weeks, 3 and 6 months after operation, where HRQol is measured with the EQ-5D questionnaire
- Health-related quality of life assessed by EORTC-QLQ-BN20 questionnaire [ Time Frame: Between baseline and 6 weeks/3 months/6 months postoperatively ]Health related quality of life (HRQoL) at 6 weeks, 3 and 6 months after operation, where HRQol is measured with the EORTC QLQ-BN20 questionnaire
- Health-related quality of life assessed by EORTC-QLQ-C30 questionnaire [ Time Frame: Between baseline and 6 weeks/3 months/6 months postoperatively ]Health related quality of life (HRQoL) at 6 weeks, 3 and 6 months after operation, where HRQol is measured with the EORTC-QLQ-C30 questionnaire
- Progression-free survival [ Time Frame: Between surgery and 12 months postoperatively ]Progression-free survival (PFS) at 12 months defined as time from diagnosis to disease progression (occurrence of a new tumour lesion with a volume greater than 0.175 cm3, or an increase in residual tumour volume of more than 25%) or death, whichever comes first
- Overall survival [ Time Frame: Between surgery and 12 months postoperatively ]Overall survival (OS) at 12 months defined as time from diagnosis to death from any cause
- Postoperative (serious) adverse events [ Time Frame: Between surgery and 6 weeks postoperatively ]Frequency and severity of (Serious) Adverse Effects in each group: Infections, intracerebral hemorrhage, epilepsy, aphasia, paresis/paralysis in arms or/and legs
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03861299
|Contact: Jasper Gerritsen, MDemail@example.com|
|University Hospital Brussels||Recruiting|
|Brussels, Belgium, 1090|
|Contact: Johnny Duerinck, MD PhD 0032486185121 firstname.lastname@example.org|
|University Hospital Ghent||Recruiting|
|Ghent, Belgium, 9000|
|Contact: Giorgio Hallaert, MD PhD 003293326876 email@example.com|
|Tilburg, Noord-Brabant, Netherlands, 5022 GC|
|Contact: Geert Jan Rutten, MD PhD +310132210000 firstname.lastname@example.org|
|Rotterdam, Zuid-Holland, Netherlands, 3015 CE|
|Contact: Arnaud Vincent, MD PhD +31639428949 email@example.com|
|Contact: Jasper Gerritsen, MD +31629119553 firstname.lastname@example.org|
|Medical Center Haaglanden||Recruiting|
|The Hague, Zuid-Holland, Netherlands, 2261 CP|
|Contact: Marike Broekman, MD PhD +31639758253 email@example.com|
|University Medical Center Groningen||Recruiting|
|Groningen, Netherlands, 9700 RB|
|Contact: Michiel Wagemakers, MD PhD +310503616161 firstname.lastname@example.org|
|Principal Investigator:||Arnaud Vincent, MD PhD||Erasmus Medical Center|