The RECSUR-study: Resection Versus Best Oncological Treatment for Recurrent Glioblastoma (ENCRAM 2302)
- Conditions
- GlioblastomaGlioblastoma MultiformeGlioblastoma, IDH-wildtypeGlioblastoma Multiforme of BrainGlioblastoma Multiforme, AdultRecurrent GlioblastomaAstrocytoma, MalignantAstrocytoma of Brain
- Interventions
- Procedure: Re-resectionRadiation: Re-irradiationProcedure: Experimental therapyOther: Best supportive care
- Registration Number
- NCT06283927
- Lead Sponsor
- Jasper Gerritsen
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 464
- Age ≥18 years and ≤90 years
- Tumor recurrence according to the RANO criteria of a previously diagnosed glioblastoma based on the WHO 2021 classification for glioma
- The tumor is suitable for resection (according to neurosurgeon)
- Written informed consent
- Tumors of the cerebellum, brainstem, or midline
- Medical reasons precluding MRI (e.g., pacemaker)
- Inability to give written informed consent
- Secondary high-grade glioma due to malignant transformation from low-grade glioma
- Clinical data unavailable for the newly diagnosed setting
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Re-resection Re-resection Resection of the recurrent tumor Best oncological treatment Re-irradiation Best oncological treatment consisting of re-challenge temozolomide, re-irradiation, experimental therapy, or best supportive care Best oncological treatment Experimental therapy Best oncological treatment consisting of re-challenge temozolomide, re-irradiation, experimental therapy, or best supportive care Best oncological treatment Best supportive care Best oncological treatment consisting of re-challenge temozolomide, re-irradiation, experimental therapy, or best supportive care Best oncological treatment Temozolomide Best oncological treatment consisting of re-challenge temozolomide, re-irradiation, experimental therapy, or best supportive care Best oncological treatment Lomustine Best oncological treatment consisting of re-challenge temozolomide, re-irradiation, experimental therapy, or best supportive care
- Primary Outcome Measures
Name Time Method Neurological morbidity at 6 weeks 6 weeks postoperatively NIHSS deterioration of 1 point or more at 6 weeks after surgery
Overall survival Up to 5 years postoperatively Time from diagnosis to death from any cause
- Secondary Outcome Measures
Name Time Method Neurological morbidity at 3 months 3 months postoperatively NIHSS deterioration of 1 point or more at 3 months after surgery
Quality of life at 6 weeks (EORTC QLQ C30) 6 weeks postoperatively Quality of life as assessed by the EORTC QLQ C30 questionnaire
Quality of life at 6 weeks (EQ-5D) 6 weeks postoperatively Quality of life as assessed by the EQ-5D questionnaire
Neurological morbidity at 6 months 6 months postoperatively NIHSS deterioration of 1 point or more at 6 months after surgery
Progression-free survival Up to 5 years postoperatively 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
Residual tumor volume Within 72 hours postoperatively 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)
Quality of life at 3 months (EORTC QLQ C30) 3 months postoperatively Quality of life as assessed by the EORTC QLQ C30 questionnaire
Quality of life at 6 months (EORTC QLQ C30) 6 months postoperatively Quality of life as assessed by the EORTC QLQ C30 questionnaire
Quality of life at 3 months (EORTC QLQ BN20) 3 months postoperatively Quality of life as assessed by the EORTC QLQ BN20 questionnaire
Quality of life at 6 weeks (EORTC QLQ BN20) 6 weeks postoperatively Quality of life as assessed by the EORTC QLQ BN20 questionnaire
Quality of life at 6 months (EORTC QLQ BN20) 6 months postoperatively Quality of life as assessed by the EORTC QLQ BN20 questionnaire
Quality of life at 6 months (EQ-5D) 6 months postoperatively Quality of life as assessed by the EQ-5D questionnaire
Quality of life at 3 months (EQ-5D) 3 months postoperatively Quality of life as assessed by the EQ-5D questionnaire
Serious Adverse Events 6 weeks postoperatively Serious Adverse Events within 6 weeks postoperatively
Trial Locations
- Locations (8)
Technical University Munich
🇩🇪Munich, Germany
Erasmus MC
🇳🇱Rotterdam, Zuid-Holland, Netherlands
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University Hospital Leuven
🇧🇪Leuven, Belgium
Medical Center Haaglanden
🇳🇱The Hague, Zuid-Holland, Netherlands
University Hospital Heidelberg
🇩🇪Heidelberg, Germany
Inselspital Universitätsspital Bern
🇨🇭Bern, Switzerland
University of California, San Francisco
🇺🇸San Francisco, California, United States