The RECMAP-study: Resection With or Without Intraoperative Mapping for Recurrent Glioblastoma

NCT ID: NCT06273176

Last Updated: 2024-02-22

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 225 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-01-01
• Study Completion Date: 2028-01-01

Brief Summary

Resection of glioblastoma in or near functional brain tissue is challenging because of the proximity of important structures to the tumor site. To pursue maximal resection in a safe manner, mapping methods have been developed to test for motor and language function during the operation. Previous evidence suggests that these techniques are beneficial for maximum safe resection in newly diagnosed grade 2-4 astrocytoma, grade 2-3 oligodendroglioma, and recently, glioblastoma. However, their effects in recurrent glioblastoma are still poorly understood. The aim of this study, therefore, is to compare the effects of awake mapping and asleep mapping with no mapping in resections for recurrent glioblastoma.

This study is an international, multicenter, prospective 3-arm cohort study of observational nature. Recurrent glioblastoma patients will be operated with mapping or no mapping techniques with a 1:1 ratio. Primary endpoints are: 1) proportion of patients with NIHSS (National Institute of Health Stroke Scale) deterioration at 6 weeks, 3 months, and 6 months after surgery and 2) residual tumor volume of the contrast-enhancing and non-contrast-enhancing part as assessed by a neuroradiologist on postoperative contrast MRI scans. Secondary endpoints are: 1) overall survival (OS), 2) progression-free survival (PFS), 4) 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 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, 3-arm cohort study. Eligible patients are operated with or without mapping techniques with a 1:1 ratio with a sequential computer-generated random number as subject ID. Patients with motor-eloquent tumors will be treated in all study arms, while speech-eloquent tumors will only be treated in either the awake mapping or no mapping arm. The RECMAP study is similar to the SAFE-trial24 (awake craniotomy versus craniotomy under general anesthesia for glioblastoma patients, NCT03861299) and is initiated by the same center, however, the presented study will be different in various ways: the RECMAP study (1) will be an observational, prospective cohort study, (2) will include asleep mapping as an additional treatment arm, (3) will evaluate the extent of resection of the non-contrast-enhancing part of the tumor as well, (4) only includes recurrent tumors (5) will include neurosurgical centers in the United States and is part of the ENCRAM Research Consortium18. The RECMAP study is also similar to the PROGRAM study25 (awake mapping versus asleep mapping versus no mapping for high-grade glioma patients, NCT04708171), with the difference that the RECMAP study includes recurrent tumors (while the PROGRAM study includes newly diagnosed tumors), and that the RECMAP study includes recurrent glioblastoma, while the PRGORAM study includes WHO grade 3 and 4 gliomas.

Study patients are operated with either awake mapping, asleep mapping or no mapping 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) scales. 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 resections with or without mapping techniques (neurological morbidity and residual CE and NCE tumor volume) in recurrent glioblastoma patients as expressed by NIHSS scores and volumetric data. Secondary study objectives are to study the overall survival (OS), progressive-free survival (PFS), health-related quality of life (HRQoL), and Serious Adverse Events (SAEs) after resections with or without mapping techniques as expressed by survival data, progression on follow up MRI scans based on the RANO criteria26 for tumor progression, quality of life questionnaires (EORTC QLQ C30, EORTC QLQ BN20, EQ-5D), and registration of SAEs.

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, IDH-wildtype; Glioblastoma; Glioblastoma Multiforme of Brain; Astrocytoma, Malignant; Brain Neoplasms; Brain Neoplasms, Adult, Malignant; Brain Neoplasms, Adult; Recurrent Adult Brain Tumor; Recurrent Glioblastoma

Study Design

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

Study Groups

Awake mapping

Awake mapping: Tumor resection with intraoperative awake motor or language mapping

Awake mapping under local anesthesia

Intervention Type: PROCEDURE

During an awake craniotomy, the patient is awake and cooperative during the resection of the tumor while the surgeon uses electro(sub)cortical mapping to prevent damage to eloquent areas.

Asleep mapping

Asleep mapping: Tumor resection with intraoperative asleep motor mapping

Asleep mapping under general anesthesia

Intervention Type: PROCEDURE

During asleep mapping under general anesthesia, the surgeon uses electro(sub)cortical mapping with evoked potentials (MEPs, SSEPs or continuous dynamic mapping) to prevent damage to eloquent areas.

No mapping

No mapping: Tumor resection without intraoperative mapping

Resection under general anesthesia without mapping

Intervention Type: PROCEDURE

During resection under general anesthesia without mapping, the surgeon does not use any intraoperative stimulation mapping techniques to identify eloquent areas.

Interventions

Awake mapping under local anesthesia

During an awake craniotomy, the patient is awake and cooperative during the resection of the tumor while the surgeon uses electro(sub)cortical mapping to prevent damage to eloquent areas.

Intervention Type: PROCEDURE

Asleep mapping under general anesthesia

During asleep mapping under general anesthesia, the surgeon uses electro(sub)cortical mapping with evoked potentials (MEPs, SSEPs or continuous dynamic mapping) to prevent damage to eloquent areas.

Intervention Type: PROCEDURE

Resection under general anesthesia without mapping

During resection under general anesthesia without mapping, the surgeon does not use any intraoperative stimulation mapping techniques to identify eloquent areas.

Intervention Type: PROCEDURE

Other Intervention Names

Awake craniotomy; Asleep motor mapping; Continous dynamic mapping; Evoked potentials

Eligibility Criteria

Inclusion Criteria

1. Age ≥18 years and ≤90 years

2. Tumor recurrence according to the RANO criteria of a previously diagnosed glioblastoma based on the WHO 2021 classification for glioma

3. Tumors situated in or near eloquent areas; motor cortex, sensory cortex, subcortical pyramidal tract, speech areas or visual areas as indicated on MRI (Sawaya Grading II and II)19

4. The tumor is suitable for resection (according to neurosurgeon)

5. 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. Clinical data unavailable for the newly diagnosed setting

• 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

Erasmus Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Jasper Gerritsen

MD PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jasper Gerritsen, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Erasmus Medical Center

Locations

University of California, San Francisco

San Francisco, California, United States

Site Status: RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

University Hospital Leuven

Leuven, , Belgium

Site Status: RECRUITING

Universitätsklinikum Heidelberg

Heidelberg, , Germany

Site Status: RECRUITING

Technical University Munich

Munich, , Germany

Site Status: NOT_YET_RECRUITING

Erasmus Medical Center

Rotterdam, South Holland, Netherlands

Site Status: RECRUITING

Haaglanden Medical Center

The Hague, , 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 PhD

Role: primary

Brian Nahed, MD PhD

Role: primary

Steven De Vleeschouwer, MD PhD

Role: primary

Christine Jungk, MD PhD

Role: primary

Sandro Krieg, MD PhD

Role: backup

Arthur Wagner, MD

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

Identifier Type: -

Identifier Source: org_study_id