Neoplasms

All Conditions

Nervous System Diseases

Symptoms and General Pathology

Behaviors and Mental Disorders

Rare Diseases

Glioblastoma

Glioma

Brain Neoplasms

Disease Progression

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Quality of Life

Neuroepithelioma

Supramaximal resection: maximal resection of the contrast-enhancing and non-contrast-enhancing part of the tumor (FLAIRectomy)

Maximal safe resection of the contrast-enhancing part of the tumor

Supramaximal resection. Tumor resection continues until either the FLAIR abnormalities have been resected based on the neuronavigation (after updating the navigation intraoperatively), or when subcortical tracts are identified with intraoperative stimulation.

Supramaximal resection

Maximal safe resection. Tumor resection continues until maximal safe resection has been achieved as by the neurosurgeon's opinion.

Maximal safe resection

Jasper Gerritsen, MD PhD

Arnaud Vincent, MD PhD

Mitchel Berger, MD

Brian Nahed, MD

Steven De Vleeschouwer, MD PhD

Christine Jungk, MD PhD

Sandro Krieg, MD MBA

Arthur Wagner, MD PhD

Marike Broekman, MD PhD

Philippe Schucht, MD PhD

A greater extent of resection of the contrast-enhancing (CE) tumor part has been associated with improved outcomes in high-grade glioma patients. Recent results suggest that resection of the non-contrast-enhancing (NCE) part might yield even better survival outcomes (supramaximal resection, SMR). Therefore, this study evaluates the efficacy and safety of SMR with and without mapping techniques in HGG patients in terms of survival, functional, neurological, cognitive, and quality of life outcomes. Furthermore, it evaluates which patients benefit the most from SMR, and how they could be identified preoperatively.

This study is an international, multicenter, prospective, 2-arm cohort study of observational nature. Consecutive HGG patients will be operated with supramaximal resection or maximal resection at a 1:3 ratio. Primary endpoints are: 1) overall survival and 2) proportion of patients with NIHSS (National Institute of Health Stroke Scale) deterioration at 6 weeks, 3 months, and 6 months postoperatively. Secondary endpoints are 1) residual CE and NCE tumor volume on postoperative T1-contrast and FLAIR MRI scans 2) progression-free survival; 3) onco-functional outcome, and 4) quality of life at 6 weeks, 3 months, and 6 months postoperatively.

The study will be carried out by the centers affiliated with the European and North American Consortium and Registry for Intraoperative Mapping (ENCRAM).

This is an international, multicenter, prospective, observational, 2-arm cohort study (registration: clinicaltrials.gov ID number TBA). Eligible patients are operated with supramaximal resection versus maximal resection with a 1:3 ratio with a sequential computer-generated random number as subject ID. Intraoperative mapping techniques and/or surgical adjuncts can be used in both treatment arms to ensure the safety of the resection (to minimize the risk of postoperative deficits). Supramaximal resection is defined as 0 cm3 CE tumor and 5 cm3 or less NCE tumor, whereas maximal resection is defined as 0 cm3 CE tumor and \>5 cm3 NCE tumor (in line with the updated RANO criteria).

Study patients are allocated to either the supramaximal or maximal safe resection group and will undergo evaluation at presentation (baseline) and during the follow-up period at 6 weeks, 3 months, and 6 months postoperatively. Motor function will be evaluated using the NIHSS (National Institute of Health Stroke Scale) scale. Language function will be evaluated using a standard neurolinguistic test-battery consisting of the Aphasia Bedside Check (ABC), Shortened Token test, Verbal fluency, Picture description and Object naming. Cognitive function will be assessed using the Montreal Cognitive Assessment (MOCA). Patient functioning with be assessed with the Karnofsky Performance Scale (KPS) and the ASA (American Society of Anesthesiologists) physical status classification system. Health-related quality of life (HRQoL) will be assessed with the EORTC QLQ C30, EORTC QLQ BN20 and EQ 5D questionnaires. Overall survival and progression-free survival will be assessed. We expect to complete patient inclusion in 4 years. The estimated duration of the study (including follow-up) will be 5 years.

The primary study objective is to evaluate the safety and efficacy of supramaximal resection versus safe maximal resection in HGG patients as measured by overall survival (OS) and postoperative NIHSS deterioration. Secondary study objectives are to evaluate extent of resection of CE and NCE tumor, quality of life, progression-free survival (PFS), onco-functional outcome (OFO), and SAEs after SMR or maximal safe resections as measured by volumetric analyses of contrast-enhanced MRI images with gadolinium combined with FLAIR images, tumor progression on MRI scans, quality of life questionnaires (EORTC QLQ C30, EORTC QLQ BN20, EQ 5D), combining postoperative residual volume with NIHSS outcomes, and recording SAEs respectively.

Patients will be recruited from the neurosurgical or neurological outpatient clinic or through referral from general hospitals of the participating neurosurgical hospitals, located in Europe and the United States. The study is carried out by centers from the ENCRAM Consortium.

The SUPRAMAX Study: Supramaximal Resection Versus Maximal Resection for High-Grade Glioma Patients (ENCRAM 2201)

The SUPRAMAX-study: Supramaximal Resection Versus Maximal Resection for High-Grade Glioma Patients (ENCRAM 2201)

Time from diagnosis to death from any cause

NIHSS deterioration of 1 point or more at 6 weeks after surgery

NIHSS deterioration of 1 point or more at 3 months after surgery

NIHSS deterioration of 1 point or more at 6 months after surgery

Time from diagnosis to disease progression (occurrence of a new tumor lesions with a volume greater than 0.175 cm3, or an increase in residual tumor volume of more than 25%) or death, whichever comes first

Residual tumor volume of the contrast-enhancing and non-contrast enhancing part, as assessed by a neuroradiologist on postoperative MRI scan (T1 with contrast and FLAIR sequences) using manual or semi-automatic volumetric analyses (Brainlab Elements iPlan CMF Segmentation, Brainlab AG, Munich, Germany; or similar software)

According to the OFO classification, consisting of the combination of presence/absence of functional deterioration with gross-total resection

Quality of life as assessed by the EORTC QLQ C30 questionnaire

Quality of life as assessed by the EORTC QLQ BN20 questionnaire

Quality of life as assessed by the EQ-5D questionnaire

Serious Adverse Events within 6 weeks postoperatively

Haaglanden Medical Centre

Universitaire Ziekenhuizen KU Leuven

University Hospital Heidelberg

Technical University of Munich

Insel Gruppe AG, University Hospital Bern

Massachusetts General Hospital

University of California, San Francisco

Jasper Gerritsen

Recurrence

Disease Attributes

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

Immunomodulating Agents

Lomustine

Antineoplastic Agents, Alkylating

Alkylating Agents

Best oncological treatment consisting of re-challenge temozolomide, re-irradiation, experimental therapy, or best supportive care

Re-resection

Re-irradiation with single dose, fractionated, or hypofractionated radiation of the recurrent tumor

Re-irradiation

Experimental phase I therapy with oncolytic virotherapy or immunotherapy (this list is not exhaustive)

Experimental therapy

Best supportive care, focused on alleviating symptoms

Best supportive care

Mitchel Berger, MD PhD

Brian Nahed, MD PhD

Christine Jungk, Dr. med.

Arthur Wagner, MD

Jasper Gerritsen, MD

Previous evidence has indicated that resection for recurrent glioblastoma might benefit the prognosis of these patients in terms of overall survival. However, the demonstrated safety profile of this approach is contradictory in the literature and the specific benefits in distinct clinical and molecular patient subgroups remains ill-defined. The aim of this study, therefore, is to compare the effects of resection and best oncological treatment for recurrent glioblastoma as a whole and in clinically important subgroups.

This study is an international, multicenter, prospective observational cohort study. Recurrent glioblastoma patients will undergo tumor resection or best oncological treatment at a 1:1 ratio as decided by the tumor board. Primary endpoints are: 1) proportion of patients with NIHSS (National Institute of Health Stroke Scale) deterioration at 6 weeks after surgery and 2) overall survival. Secondary endpoints are: 1) progression-free survival (PFS), 2) NIHSS deterioration at 3 months and 6 months after surgery, 3) health-related quality of life (HRQoL) at 6 weeks, 3 months, and 6 months after surgery, and 4) frequency and severity of Serious Adverse Events (SAEs) in each arm. Estimated total duration of the study is 5 years. Patient inclusion is 4 years, follow-up is 1 year.

The study has been approved by the Medical Ethics Committee (METC Zuid-West Holland/Erasmus Medical Center; MEC-2020-0812). The results will be published in peer-reviewed academic journals and disseminated to patient organisations and media.

This is an international, multicenter, prospective, cohort study. Eligible patients are operated or receive best oncological treatment with a 1:1 ratio with a sequential computer-generated random number as subject ID. Intraoperative mapping techniques and/or surgical adjuncts can be used in both treatment arms to ensure the safety of the resection (to minimize the risk of postoperative deficits).

Study patients undergo tumor re-resection or receive best oncological treatment and will undergo evaluation at presentation (baseline) and during the follow-up period at 6 weeks, 3 months, and 6 months postoperatively. Motor function will be evaluated using the NIHSS (National Institute of Health Stroke Scale) and MRC (Medical Research Council) scale. Language function will be evaluated using a standard neurolinguistic test-battery consisting of the Aphasia Bedside Check (ABC), Shortened Token test, Verbal fluency, Picture description and Object naming. This neurolinguistic test-battery is the result of a consensus between the participating centers. Cognitive function will be assessed using the Montreal Cognitive Assessment (MOCA). Overall patient functioning with be assessed with the Karnofsky Performance Scale (KPS) and the ASA (American Society of Anesthesiologists) physical status classification system for comorbidities. Health-related quality of life (HRQoL) will be assessed with the EQ-5D questionnaire and the EORTC QLQ-C30 and EORTC QLQ-BN20 questionnaires. Overall survival and progression-free survival will be assessed. We expect to complete patient inclusion in 4 years. The estimated duration of the study, including follow-up, will be 5 years.

The primary study objective is to evaluate the safety and efficacy of re-resection versus best oncological treatment (neurological morbidity and overall survival) in recurrent glioblastoma patients as expressed by NIHSS scores and survival data. Secondary study objectives are to study the overall progressive-free survival (PFS), long-term neurological morbidity (3 months and 6 months postoperatively), health-related quality of life (HRQoL), and Serious Adverse Events (SAEs) after resection versus best oncological treatment as expressed by progression on follow up MRI scans based on the RANO criteria24 for tumor progression; NIHSS scores, quality of life questionnaires (EORTC QLQ C30, EORTC QLQ BN20, EQ-5D), and registration of SAEs.

Patients will be recruited for the study from the neurosurgical or neurological outpatient clinic or through referral from general hospitals of the participating neurosurgical hospitals of the ENCRAM Research Consortium, located in Europe and the United States.

The RECSUR-study: Resection Versus Best Oncological Treatment for Recurrent Glioblastoma (ENCRAM 2302)

The RECSUR-study: Resection Versus Best Oncological Treatment for Recurrent Glioblastoma: Study Protocol for An International Multicenter Prospective Cohort Study (ENCRAM 2302)

Postoperative Complications

Central Nervous System Depressants

Anesthetics

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.

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

Awake craniotomy

Craniotomy under general anesthesia

Giorgio Hallaert, MD PhD

Geert Jan Rutten, MD PhD

Michiel Wagemakers, MD PhD

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.

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

1. Proportion of patients with NIHSS deterioration at 6 weeks post-surgery
2. 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.

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

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

The SAFE-Trial: Safe Surgery for Glioblastoma Multiforme: Awake Craniotomy Versus Surgery Under General Anesthesia. A Multicenter Prospective Randomised Controlled Study

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 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 (HRQoL) at 6 weeks, 3 and 6 months after operation, where HRQol is measured with the EQ-5D questionnaire

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 (HRQoL) at 6 weeks, 3 and 6 months after operation, where HRQol is measured with the EORTC-QLQ-C30 questionnaire

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 (OS) at 12 months defined as time from diagnosis to death from any cause

Frequency and severity of (Serious) Adverse Effects in each group: Infections, intracerebral hemorrhage, epilepsy, aphasia, paresis/paralysis in arms or/and legs

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The SUPRAMAX Study: Supramaximal Resection Versus Maximal Resection for High-Grade Glioma Patients (ENCRAM 2201)	NCT06118723	Glioblastoma High-grade Glio... Glioblastoma, I... Glioblastoma, I... Glioblastoma Mu... Astrocytoma, Gr... Astrocytoma, Gr... Astrocytoma, Ma... Brain Neoplasms Brain Neoplasm,... Brain Neoplasms... Brain Neoplasm,...	Supramaximal re... Maximal safe re...	18 Years - 90 Years	Erasmus Medical Center
The SUPRAMAX Study: Supramaximal Resection Versus Maximal Resection for High-Grade Glioma Patients (ENCRAM 2201)	NCT06118723	Glioblastoma High-grade Glio... Glioblastoma, I... Glioblastoma, I... Glioblastoma Mu... Astrocytoma, Gr... Astrocytoma, Gr... Astrocytoma, Ma... Brain Neoplasms Brain Neoplasm,... Brain Neoplasms... Brain Neoplasm,...	Supramaximal re... Maximal safe re...	18 Years - 90 Years	Erasmus Medical Center
The RECSUR-study: Resection Versus Best Oncological Treatment for Recurrent Glioblastoma (ENCRAM 2302)	NCT06283927	Glioblastoma Glioblastoma Mu... Glioblastoma, I... Glioblastoma Mu... Glioblastoma Mu... Recurrent Gliob... Astrocytoma, Ma... Astrocytoma of ...	Re-resection Temozolomide Lomustine Re-irradiation Experimental th... Best supportive...	18 Years - 90 Years	Erasmus Medical Center
The SAFE-Trial: Awake Craniotomy Versus Surgery Under General Anesthesia for Glioblastoma Patients.	NCT03861299	Glioblastoma Glioblastoma Mu... Glioblastoma Mu... Astrocytoma, Gr... Brain Tumor Brain Cancer Brain Neoplasms	Awake craniotom... Craniotomy unde...	18 Years - 90 Years	Erasmus Medical Center

Spots Global Cancer Trial Database for neurological morbidity