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

NCT ID: NCT06118723

Last Updated: 2024-02-22

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 784 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-01-01
• Study Completion Date: 2028-01-01

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.

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Supramaximal resection

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

Supramaximal resection

Intervention Type: PROCEDURE

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 of the contrast-enhancing part of the tumor

Maximal safe resection

Intervention Type: PROCEDURE

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

Interventions

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.

Intervention Type: PROCEDURE

Maximal safe resection

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

Intervention Type: PROCEDURE

Other Intervention Names

Supramarginal resection; FLAIRectomy; Resection of the non-contrast-enhancing tumor

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Haaglanden Medical Centre

OTHER

Sponsor Role: collaborator

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role: collaborator

University Hospital Heidelberg

OTHER

Sponsor Role: collaborator

Technical University of Munich

OTHER

Sponsor Role: collaborator

Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: collaborator

Jasper Gerritsen

OTHER

Sponsor Role: lead

Responsible Party

Jasper Gerritsen

Dr.

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jasper Gerritsen, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Erasmus Medical Center

Locations

University of California, San Francisco (UCSF)

San Francisco, California, United States

Site Status: RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

University Hospitals Leuven

Leuven, , Belgium

Site Status: RECRUITING

Universitätsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, Germany

Site Status: RECRUITING

Technical University Munich

Munich, Bavaria, Germany

Site Status: NOT_YET_RECRUITING

Erasmus Medical Center

Rotterdam, South Holland, Netherlands

Site Status: RECRUITING

Haaglanden Medical Centre

The Hague, South Holland, Netherlands

Site Status: RECRUITING

Inselspital Universitätsspital Bern

Bern, , Switzerland

Site Status: NOT_YET_RECRUITING

Countries

United States; Belgium; Germany; Netherlands; Switzerland

Central Contacts

Jasper Gerritsen, MD PhD

Role: CONTACT

j.gerritsen@erasmusmc.nl

+31107036130

Arnaud Vincent, MD PhD

Role: CONTACT

a.vincent@erasmusmc.nl

+31107034211

Facility Contacts

Mitchel Berger, MD

Role: primary

Brian Nahed, MD

Role: primary

Steven De Vleeschouwer, MD PhD

Role: primary

Christine Jungk, MD PhD

Role: primary

Sandro Krieg, MD MBA

Role: backup

Arthur Wagner, MD PhD

Role: primary

Jasper Gerritsen, MD PhD

Role: primary

Marike Broekman, MD PhD

Role: primary

Philippe Schucht, MD PhD

Role: primary

Other Identifiers

MEC-2020-0812-2

Identifier Type: -

Identifier Source: org_study_id