Clinical trial NCT06283927: The RECSUR-study: Resection Versus Best Oncological Treatment for Recurrent Glioblastoma (ENCRAM 2302)
Official title: The RECSUR-study: Resection Versus Best Oncological Treatment for Recurrent Glioblastoma: Study Protocol for An International Multicenter Prospective Cohort Study (ENCRAM 2302)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Glioblastoma
Glioblastoma Multiforme
Glioblastoma, IDH-wildtype
Glioblastoma Multiforme of Brain
Glioblastoma Multiforme, Adult
Recurrent Glioblastoma
Astrocytoma, Malignant
Astrocytoma of Brain
Keywords: Glioblastoma
Radiotherapy
Chemotherapy
Re-resection
Resection
Overall survival
Progression-free survival
Neurological morbidity
Safety
Serious Adverse Events
Quality of life
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: 2024-02-28
Enrollment: 464
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 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: Previous evidence has indicated that resection for recurrent glioblastoma might benefit the prognosis of these patients in terms of overall survival. However, the demonstrated safety profile of this approach is contradictory in the literature and the specific benefits in distinct clinical and molecular patient subgroups remains ill-defined. The aim of this study, therefore, is to compare the effects of resection and best oncological treatment for recurrent glioblastoma as a whole and in clinically important subgroups.

This study is an international, multicenter, prospective observational cohort study. Recurrent glioblastoma patients will undergo tumor resection or best oncological treatment at a 1:1 ratio as decided by the tumor board. Primary endpoints are: 1) proportion of patients with NIHSS (National Institute of Health Stroke Scale) deterioration at 6 weeks after surgery and 2) overall survival. Secondary endpoints are: 1) progression-free survival (PFS), 2) NIHSS deterioration at 3 months and 6 months after surgery, 3) 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 has been approved by the Medical Ethics Committee (METC Zuid-West Holland/Erasmus Medical Center; MEC-2020-0812). The results will be published in peer-reviewed academic journals and disseminated to patient organisations and media.

Detailed description: This is an international, multicenter, prospective, cohort study. Eligible patients are operated or receive best oncological treatment with a 1:1 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).

Study patients undergo tumor re-resection or receive best oncological treatment 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) 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. 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 re-resection versus best oncological treatment (neurological morbidity and overall survival) in recurrent glioblastoma patients as expressed by NIHSS scores and survival data. Secondary study objectives are to study the overall progressive-free survival (PFS), long-term neurological morbidity (3 months and 6 months postoperatively), health-related quality of life (HRQoL), and Serious Adverse Events (SAEs) after resection versus best oncological treatment as expressed by progression on follow up MRI scans based on the RANO criteria24 for tumor progression; NIHSS scores, quality of life questionnaires (EORTC QLQ C30, EORTC QLQ BN20, EQ-5D), and registration of SAEs.

Patients will be recruited for the study from the neurosurgical or neurological outpatient clinic or through referral from general hospitals of the participating neurosurgical hospitals of the ENCRAM Research Consortium, located in Europe and the United States.

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

Exclusion Criteria:

1. Tumors of the cerebellum, brainstem, or midline
2. Medical reasons precluding MRI (e.g., pacemaker)
3. Inability to give written informed consent
4. Secondary high-grade glioma due to malignant transformation from low-grade glioma
5. Clinical data unavailable for the newly diagnosed setting

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: 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
measure: Serious Adverse Events
timeFrame: 6 weeks 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: University Hospital Heidelberg
city: Munich
country: Germany
facility: Technical University Munich
city: Rotterdam
country: Netherlands
facility: Erasmus MC
state: Zuid-Holland
city: The Hague
country: Netherlands
facility: Medical Center Haaglanden
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: