The RECSUR-study: Resection Versus Best Oncological Treatment for Recurrent Glioblastoma (ENCRAM 2302)

Glioblastoma Clinical Trial

— RECSUR  

Official title:

The RECSUR-study: Resection Versus Best Oncological Treatment for Recurrent Glioblastoma: Study Protocol for An International Multicenter Prospective Cohort Study (ENCRAM 2302)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06283927
• Other study ID #: MEC-2020-0812-5
• Status: Recruiting
• Start date: January 1, 2023
• Est. completion date: January 1, 2028

Study information

• Verified date: February 2024
• Source: Erasmus Medical Center
• Contact: Jasper Gerritsen, MD PhD
• Phone: 31107036130
• Email: j.gerritsen[@]erasmusmc.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 464
• Est. completion date: January 1, 2028
• Est. primary completion date: January 1, 2027
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Astrocytoma
• Astrocytoma of Brain
• Glioblastoma
• Glioblastoma Multiforme
• Glioblastoma Multiforme of Brain
• Glioblastoma Multiforme, Adult
• Glioblastoma, IDH-wildtype
• Recurrence
• Recurrent Glioblastoma

Intervention

Procedure:
• Re-resection
Resection of the recurrent tumor

Drug:
• Temozolomide
Re-challenge Temozolomide chemotherapy
• Lomustine
Second line chemotherapy with Lomustine

Radiation:
• Re-irradiation
Re-irradiation with single dose, fractionated, or hypofractionated radiation of the recurrent tumor

Procedure:
• Experimental therapy
Experimental phase I therapy with oncolytic virotherapy or immunotherapy (this list is not exhaustive)

Other:
• Best supportive care
Best supportive care, focused on alleviating symptoms

Locations

Country	Name	City	State
Belgium	University Hospital Leuven	Leuven
Germany	University Hospital Heidelberg	Heidelberg
Germany	Technical University Munich	Munich
Netherlands	Erasmus MC	Rotterdam	Zuid-Holland
Netherlands	Medical Center Haaglanden	The Hague	Zuid-Holland
Switzerland	Inselspital Universitätsspital Bern	Bern
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of California, San Francisco	San Francisco	California

Sponsors (8)

Lead Sponsor	Collaborator
Jasper Gerritsen	Haaglanden Medical Centre, Insel Gruppe AG, University Hospital Bern, Massachusetts General Hospital, Technical University of Munich, Universitaire Ziekenhuizen KU Leuven, University Hospital Heidelberg, University of California, San Francisco

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Netherlands,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	Time from diagnosis to death from any cause	Up to 5 years postoperatively
Primary	Neurological morbidity at 6 weeks	NIHSS deterioration of 1 point or more at 6 weeks after surgery	6 weeks postoperatively
Secondary	Neurological morbidity at 3 months	NIHSS deterioration of 1 point or more at 3 months after surgery	3 months postoperatively
Secondary	Neurological morbidity at 6 months	NIHSS deterioration of 1 point or more at 6 months after surgery	6 months postoperatively
Secondary	Progression-free survival	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	Up to 5 years postoperatively
Secondary	Residual tumor volume	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)	Within 72 hours postoperatively
Secondary	Quality of life at 6 weeks (EORTC QLQ C30)	Quality of life as assessed by the EORTC QLQ C30 questionnaire	6 weeks postoperatively
Secondary	Quality of life at 3 months (EORTC QLQ C30)	Quality of life as assessed by the EORTC QLQ C30 questionnaire	3 months postoperatively
Secondary	Quality of life at 6 months (EORTC QLQ C30)	Quality of life as assessed by the EORTC QLQ C30 questionnaire	6 months postoperatively
Secondary	Quality of life at 6 weeks (EORTC QLQ BN20)	Quality of life as assessed by the EORTC QLQ BN20 questionnaire	6 weeks postoperatively
Secondary	Quality of life at 3 months (EORTC QLQ BN20)	Quality of life as assessed by the EORTC QLQ BN20 questionnaire	3 months postoperatively
Secondary	Quality of life at 6 months (EORTC QLQ BN20)	Quality of life as assessed by the EORTC QLQ BN20 questionnaire	6 months postoperatively
Secondary	Quality of life at 6 weeks (EQ-5D)	Quality of life as assessed by the EQ-5D questionnaire	6 weeks postoperatively
Secondary	Quality of life at 3 months (EQ-5D)	Quality of life as assessed by the EQ-5D questionnaire	3 months postoperatively
Secondary	Quality of life at 6 months (EQ-5D)	Quality of life as assessed by the EQ-5D questionnaire	6 months postoperatively
Secondary	Serious Adverse Events	Serious Adverse Events within 6 weeks postoperatively	6 weeks postoperatively