Clinical trial NCT06118723: The SUPRAMAX Study: Supramaximal Resection Versus Maximal Resection for High-Grade Glioma Patients (ENCRAM 2201)
Official title: The SUPRAMAX-study: Supramaximal Resection Versus Maximal Resection for High-Grade Glioma Patients (ENCRAM 2201)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Glioblastoma
High-grade Glioma
Glioblastoma, IDH-wildtype
Glioblastoma, IDH-mutant
Glioblastoma Multiforme, Adult
Astrocytoma, Grade IV
Astrocytoma, Grade III
Astrocytoma, Malignant
Brain Neoplasms
Brain Neoplasm, Primary
Brain Neoplasms, Adult
Brain Neoplasm, Malignant
Keywords: Glioblastoma
Supramaximal resection
FLAIRectomy
Non-contrast enhancement
Neurological morbidity
Quality of life
Overall survival
Progression-free survival
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
Collaborators: name: Haaglanden Medical Centre
name: Universitaire Ziekenhuizen KU Leuven
name: University Hospital Heidelberg
name: Technical University of Munich
name: Insel Gruppe AG, University Hospital Bern
name: Massachusetts General Hospital
name: University of California, San Francisco
First posted: 2023-11-07
Enrollment: 784
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with primary high-grade glioma 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.

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years and ≤90 years
2. Tumor diagnosed as HGG (WHO grade III/IV) on MRI as assessed by the neurosurgeon
3. Written informed consent

Exclusion Criteria:

1. Tumors of the cerebellum, brainstem or midline
2. Multifocal contrast enhancing lesions
3. Medical reasons precluding MRI (e.g. pacemaker)
4. Inability to give written informed consent
5. Secondary high-grade glioma due to malignant transformation from low-grade glioma
6. 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

Primary outcomes:
measure: Overall survival
timeFrame: Up to 5 years postoperatively
measure: Neurological morbidity at 6 weeks
timeFrame: 6 weeks postoperatively
Secondary outcomes:
measure: Neurological morbidity at 3 months
timeFrame: 3 months postoperatively
measure: Neurological morbidity at 6 months
timeFrame: 6 months postoperatively
measure: Progression-free survival
timeFrame: Up to 5 years postoperatively
measure: Residual tumor volume
timeFrame: Within 72 hours postoperatively
measure: Onco-functional outcome
timeFrame: 6 weeks postoperatively
measure: Quality of life at 6 weeks (EORTC QLQ C30)
timeFrame: 6 weeks postoperatively
measure: Quality of life at 6 weeks (EORTC QLQ BN20)
timeFrame: 6 weeks postoperatively
measure: Quality of life at 6 weeks (EQ-5D)
timeFrame: 6 weeks postoperatively
measure: Quality of life at 3 months (EORTC QLQ C30)
timeFrame: 3 months postoperatively
measure: Quality of life at 3 months (EORTC QLQ BN20)
timeFrame: 3 months postoperatively
measure: Quality of life at 3 months (EQ-5D)
timeFrame: 3 months postoperatively
measure: Quality of life at 6 months (EORTC QLQ C30)
timeFrame: 6 months postoperatively
measure: Quality of life at 6 months (EORTC QLQ BN20)
timeFrame: 6 months postoperatively
measure: Quality of life at 6 months (EQ-5D)
timeFrame: 6 months postoperatively
measure: Serious Adverse Events
timeFrame: 6 weeks postoperatively
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco (UCSF)
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Leuven
country: Belgium
facility: University Hospitals Leuven
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
state: Baden-Württemberg
city: Munich
country: Germany
facility: Technical University Munich
state: Bavaria
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
state: Zuid-Holland
city: The Hague
country: Netherlands
facility: Haaglanden Medical Centre
state: Zuid-Holland
city: Bern
country: Switzerland
facility: Inselspital Universitätsspital Bern
Study officials:
affiliation: Erasmus Medical Center
name: Jasper Gerritsen, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: