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

Glioblastoma Clinical Trial

— SUPRAMAX  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06118723
• Other study ID #: MEC-2020-0812-2
• Status: Recruiting
• Start date: January 1, 2022
• Est. completion date: January 1, 2028

Study information

• Verified date: February 2024
• Source: Erasmus Medical Center
• Contact: Jasper Gerritsen, MD PhD
• Phone: +31107036130
• Email: j.gerritsen[@]erasmusmc.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 784
• Est. completion date: January 1, 2028
• Est. primary completion date: January 1, 2027
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Astrocytoma
• Astrocytoma, Grade III
• Astrocytoma, Grade IV
• Brain Neoplasm, Malignant
• Brain Neoplasm, Primary
• Brain Neoplasms
• Glioblastoma
• Glioblastoma Multiforme, Adult
• Glioblastoma, IDH-mutant
• Glioblastoma, IDH-wildtype
• Glioma
• High-grade Glioma
• Neoplasms

Intervention

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

Locations

Country	Name	City	State
Belgium	University Hospitals Leuven	Leuven
Germany	Universitätsklinikum Heidelberg	Heidelberg	Baden-Württemberg
Germany	Technical University Munich	Munich	Bavaria
Netherlands	Erasmus Medical Center	Rotterdam	Zuid-Holland
Netherlands	Haaglanden Medical Centre	The Hague	Zuid-Holland
Switzerland	Inselspital Universitätsspital Bern	Bern
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of California, San Francisco (UCSF)	San Francisco	California

Sponsors (8)

Lead Sponsor	Collaborator
Jasper Gerritsen	Haaglanden Medical Centre, Insel Gruppe AG, University Hospital Bern, Massachusetts General Hospital, Technical University of Munich, Universitaire Ziekenhuizen KU Leuven, University Hospital Heidelberg, University of California, San Francisco

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Netherlands,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	Time from diagnosis to death from any cause	Up to 5 years postoperatively
Primary	Neurological morbidity at 6 weeks	NIHSS deterioration of 1 point or more at 6 weeks after surgery	6 weeks postoperatively
Secondary	Neurological morbidity at 3 months	NIHSS deterioration of 1 point or more at 3 months after surgery	3 months postoperatively
Secondary	Neurological morbidity at 6 months	NIHSS deterioration of 1 point or more at 6 months after surgery	6 months postoperatively
Secondary	Progression-free survival	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	Up to 5 years postoperatively
Secondary	Residual tumor volume	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)	Within 72 hours postoperatively
Secondary	Onco-functional outcome	According to the OFO classification, consisting of the combination of presence/absence of functional deterioration with gross-total resection	6 weeks postoperatively
Secondary	Quality of life at 6 weeks (EORTC QLQ C30)	Quality of life as assessed by the EORTC QLQ C30 questionnaire	6 weeks postoperatively
Secondary	Quality of life at 6 weeks (EORTC QLQ BN20)	Quality of life as assessed by the EORTC QLQ BN20 questionnaire	6 weeks postoperatively
Secondary	Quality of life at 6 weeks (EQ-5D)	Quality of life as assessed by the EQ-5D questionnaire	6 weeks postoperatively
Secondary	Quality of life at 3 months (EORTC QLQ C30)	Quality of life as assessed by the EORTC QLQ C30 questionnaire	3 months postoperatively
Secondary	Quality of life at 3 months (EORTC QLQ BN20)	Quality of life as assessed by the EORTC QLQ BN20 questionnaire	3 months postoperatively
Secondary	Quality of life at 3 months (EQ-5D)	Quality of life as assessed by the EQ-5D questionnaire	3 months postoperatively
Secondary	Quality of life at 6 months (EORTC QLQ C30)	Quality of life as assessed by the EORTC QLQ C30 questionnaire	6 months postoperatively
Secondary	Quality of life at 6 months (EORTC QLQ BN20)	Quality of life as assessed by the EORTC QLQ BN20 questionnaire	6 months postoperatively
Secondary	Quality of life at 6 months (EQ-5D)	Quality of life as assessed by the EQ-5D questionnaire	6 months postoperatively
Secondary	Serious Adverse Events	Serious Adverse Events within 6 weeks postoperatively	6 weeks postoperatively