Clinical trial NCT06273176: The RECMAP-study: Resection With or Without Intraoperative Mapping for Recurrent Glioblastoma
Official title: The RECMAP-study: Resection With or Without Intraoperative Mapping for Recurrent Glioblastoma: Study Protocol for An International Multicenter Prospective Cohort Study (ENCRAM 2301)
Study type: OBSERVATIONAL
Overall status: RECRUITING
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
Keywords: Glioblastoma
Recurrent
Re-resection
Resection
Intraoperative mapping
Awake mapping
Awake craniotomy
Asleep mapping
Motor mapping
Language mapping
Overall survival
Progression-free survival
Neurological morbidity
Quality of life
Functional area
Eloquent
Extent of resection
Residual tumor volume
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: 2024-02-22
Enrollment: 225
Sex: ALL
Maximum age (years): 90
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with recurrent glioblastoma 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: 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.

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

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