The SAFE-Trial: Awake Craniotomy Versus Surgery Under General Anesthesia for Glioblastoma Patients.

NCT03861299 | Recruiting

• 2 other identifiers: NL66673.078.18MEC-2018-1564
• Study Type: interventional
• Target: 246
• Locations: 2 countries
• Sites: 5

Brief Summary

The trial is designed as a multicenter randomized controlled study. 246 patients with presumed Glioblastoma Multiforme in eloquent areas on diagnostic MRI will be selected by the neurosurgeons according the eligibility criteria (see under). After written informed consent is obtained, the patient will be randomized for an awake craniotomy (AC) (+/-123 patients) or craniotomy under general anesthesia (GA) (+/-123 patients), with 1:1 allocation ratio. Under GA the amount of resection of the tumour has to be performed within safe margins as judged by the surgeon during surgery. The second group will be operated with an awake craniotomy procedure where the resection boundaries for motor or language functions will be identified by direct cortical and subcortical stimulation. After surgery, the diagnosis of GBM will have to be histologically confirmed. If GBM is not histologically confirmed, patients will be considered off-study and withdrawn from the study. These patients will be followed-up according to standard practice. 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 expected to take 4 years. Follow-up is 1 year after surgery. Statistical analysis, cost benefit analysis and article writing will take 3 months.

Conditions

Glioblastoma; Glioblastoma Multiforme; Glioblastoma Multiforme of Brain; Astrocytoma, Grade IV; Brain Tumor; Brain Cancer; Brain Neoplasms

Keywords

Glioblastoma; Neurological morbidity; Postoperative complications; Extent of resection; Gross-total resection; Health-related quality of life; Progression-free survival; Overall survival

Outcome Measures

Primary Outcomes (2)

• Postoperative neurological morbidity

  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

  Between operation and 6 weeks postoperatively

• Proportion of gross-total resections

  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.

  Assessed on 48 hours postoperative scan

Secondary Outcomes (6)

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

  Between baseline and 6 weeks/3 months/6 months postoperatively

• Health-related quality of life assessed by EORTC-QLQ-BN20 questionnaire

  Between baseline and 6 weeks/3 months/6 months postoperatively

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

  Between baseline and 6 weeks/3 months/6 months postoperatively

• Progression-free survival

  Between surgery and 12 months postoperatively

• Overall survival

  Between surgery and 12 months postoperatively

Study Arms (2)

Awake craniotomy

EXPERIMENTAL

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

Craniotomy under general anesthesia

ACTIVE COMPARATOR

Trephination and tumour resection are performed without any additional neuro-psychological monitoring or brain mapping, guided by STEALTH-neuronavigation.

Procedure: Craniotomy under general anesthesia

Interventions

Awake craniotomy PROCEDURE

Awake craniotomy

Also known as: Intraoperative stimulation monitoring with (sub)cortical electrostimulation, Intraoperative brain mapping with (sub)cortical electrostimulation

Awake craniotomy

Craniotomy under general anesthesia PROCEDURE

Craniotomy under general anesthesia

Craniotomy under general anesthesia

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years and ≤ 90 years
• Tumor diagnosed as Glioblastoma Multiforme on MRI with distinct ring-like pattern of contrast enhancement with thick irregular walls and a core area reduced signal suggestive of tumour necrosis as assessed by the surgeon
• Tumors situated in or near eloquent areas; motor cortex, sensory cortex, subcortical pyramidal tract or speech areas as indicated on MRI (Sawaya Grading II and II)
• The tumor is suitable for resection (according to neurosurgeon)
• Karnofsky performance scale 80 or more
• Written Informed consent

You may not qualify if:

• Tumors of the cerebellum, brain stem or midline
• Multifocal contrast enhancing lesions
• Substantial non-contrast enhancing tumor areas suggesting low grade gliomas with malignant transformation
• Medical reasons precluding MRI (eg, pacemaker)
• Inability to give consent because of or language barrier
• Psychiatric history
• Previous brain tumour surgery
• Previous low-grade glioma.
• Second primary malignancy within the past 5 years with the exception of adequately treated in situ carcinoma of any organ or basal cell carcinoma of the skin.
• Severe aphasia or dysphasia

Sponsors & Collaborators

• Jasper Gerritsen: lead
• Elisabeth-TweeSteden Ziekenhuis: collaborator
• University Medical Center Groningen: collaborator
• Medical Center Haaglanden: collaborator
• University Hospital, Ghent: collaborator

Study Sites (5)

University Hospital Ghent

Ghent, 9000, Belgium

RECRUITING

Elisabeth-Tweesteden Ziekenhuis

Tilburg, North Brabant, 5022 GC, Netherlands

RECRUITING

Erasmus MC

Rotterdam, South Holland, 3015 CE, Netherlands

RECRUITING

Medical Center Haaglanden

The Hague, South Holland, 2261 CP, Netherlands

RECRUITING

University Medical Center Groningen

Groningen, 9700 RB, Netherlands

RECRUITING

Related Publications (3)

• Gerritsen JKW, Zwarthoed RH, Kilgallon JL, Nawabi NL, Jessurun CAC, Versyck G, Pruijn KP, Fisher FL, Lariviere E, Solie L, Mekary RA, Satoer DD, Schouten JW, Bos EM, Kloet A, Nandoe Tewarie R, Smith TR, Dirven CMF, De Vleeschouwer S, Broekman MLD, Vincent AJPE. Effect of awake craniotomy in glioblastoma in eloquent areas (GLIOMAP): a propensity score-matched analysis of an international, multicentre, cohort study. Lancet Oncol. 2022 Jun;23(6):802-817. doi: 10.1016/S1470-2045(22)00213-3. Epub 2022 May 12.

  PMID: 35569489 DERIVED

• Gerritsen JKW, Dirven CMF, De Vleeschouwer S, Schucht P, Jungk C, Krieg SM, Nahed BV, Berger MS, Broekman MLD, Vincent AJPE. The PROGRAM study: awake mapping versus asleep mapping versus no mapping for high-grade glioma resections: study protocol for an international multicenter prospective three-arm cohort study. BMJ Open. 2021 Jul 21;11(7):e047306. doi: 10.1136/bmjopen-2020-047306.

  PMID: 34290067 DERIVED

• Gerritsen JKW, Klimek M, Dirven CMF, Hoop EO, Wagemakers M, Rutten GJM, Kloet A, Hallaert GG, Vincent AJPE. The SAFE-trial: Safe surgery for glioblastoma multiforme: Awake craniotomy versus surgery under general anesthesia. Study protocol for a multicenter prospective randomized controlled trial. Contemp Clin Trials. 2020 Jan;88:105876. doi: 10.1016/j.cct.2019.105876. Epub 2019 Oct 30.

  PMID: 31676314 DERIVED

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms; Postoperative Complications

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Arnaud Vincent, MD PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jasper Gerritsen, MD PhD

CONTACT

+31629119553; j.gerritsen@erasmusmc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Study Coordinator

Model Details: 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

Study Record Dates

• First Submitted: February 28, 2019
• First Posted: March 4, 2019
• Study Start: April 1, 2019
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: November 21, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share

Locations

BE (1); NL (4)