Clinical trial NCT06146725: The RESBIOP-study: Resection Versus Biopsy in High-grade Glioma Patients (ENCRAM 2202)
Official title: The RESBIOP-study: Resection Versus Biopsy in High-grade Glioma Patients (ENCRAM 2202)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Glioblastoma
Glioblastoma, IDH-wildtype
Glioblastoma Multiforme
Glioblastoma Multiforme, Adult
Glioblastoma Multiforme of Brain
Keywords: Resection
Biopsy
Survival
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: 2023-11-27
Enrollment: 564
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 primary high-grade glioma 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: There are no guidelines or prospective studies defining the optimal surgical treatment for gliomas of older patients (≥70 years) or those with limited functioning performance at presentation (KPS ≤70). Therefore, the decision between resection and biopsy is varied, amongst neurosurgeons internationally and at times even within an instiutition. This study aims to compare the effects of maximal tumor resection versus tissue biopsy on survival, functional, neurological, and quality of life outcomes in these patient subgroups. Furthermore, it evaluates which modality would maximize the potential to undergo adjuvant treatment.

This study is an international, multicenter, prospective, 2-arm cohort study of observational nature. Consecutive HGG patients will be treated with resection or biopsy at a 3:1 ratio. Primary endpoints are: 1) overall survival (OS) and 2) proportion of patients that have received adjuvant treatment with chemotherapy and radiotherapy. Secondary 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 2) progression-free survival (PFS); 3) quality of life at 6 weeks, 3 months and 6 months after surgery and 4) frequency and severity of Serious Adverse Events (SAEs). Total duration of the study is 5 years. Patient inclusion is 4 years, follow-up is 1 year.

Detailed description: Trial design This is an international, multicenter, prospective, observational, 2-arm cohort study (registration: clinicaltrials.gov ID number TBA). Eligible patients are treated with either resection or biopsy with a 3:1 ratio with a sequential computer-generated random number as subject ID.

Study objectives The primary study objective is to evaluate safety and efficacy of resection versus biopsy in HGG patients as measured by overall survival (OS) and receipt of adjuvant treatment with chemotherapy and radiotherapy. Secondary study objectives are to evaluate postoperative neurological morbidity, progression-free survival (PFS), postoperative quality of life and SAEs after resection or biopsy as measured by NIHSS deteriration, tumor progression on MRI scans, quality of life questionnaires (QLQ C30, EORTC QLQ BN20, EQ 5D), and recording SAEs respectively.

Study setting and participants 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.

Study patients are allocated to either the supramaximal or maximum safe resection group and will undergo evaluation at presentation (baseline) and during the follow-up period at 6 weeks, 3 months, 6 months and 12 months postoperatively. Motor function will be evaluated using the NIHSS (National Institute of Health Stroke Scale) scale. Cognitive function will be assessed using the Montreal Cognitive Assessment (MOCA). Patient functioning with be assessed with the Karnofsky Performance Scale (KPS) and the ASA (American Society of Anesthesiologists) physical status classification system. Health-related quality of life (HRQoL) will be assessed with the EORTC QLQ C30, EORTC QLQ BN20 and EQ 5D questionnaires. Overall survival and progression-free survival will be assessed at 12 months postoperatively. We expect to complete patient inclusion in 4 years. The estimated duration of the study (including follow-up) will be 5 years.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years and ≤90 years
2. Tumor diagnosed as HGG (WHO grade III/IV) on MRI as assessed by the neurosurgeon
3. 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. Second primary malignancy within the past 5 years with the exception of adequately treated in situ carcinoma of any organ or basal cell carcinoma of the skin

Primary outcomes:
measure: Overall survival
timeFrame: Up to 5 years postoperatively
measure: Adjuvant treatment with chemotherapy and radiotherapy
timeFrame: 6 months postoperatively
Secondary outcomes:
measure: Progression-free survival
timeFrame: Up to 5 years postoperatively
measure: Neurological morbidity at 6 weeks
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: 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: Munich
country: Germany
facility: Technical University Munich
state: Bavaria
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg
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: