The RESBIOP-study: Resection Versus Biopsy in High-grade Glioma Patients (ENCRAM 2202) (RESBIOP)

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.

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma; Glioblastoma Multiforme; Glioblastoma, IDH-wildtype; Glioblastoma Multiforme, Adult; Glioblastoma Multiforme of Brain
• Intervention / Treatment: Procedure: Tumor resection; Procedure: Tumor biopsy

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.

• Study Type: Observational
• Enrollment (Estimated): 564

Contacts and Locations

• Study Contact: Name: Jasper Gerritsen, MD PhD; Phone Number: +31107036130; Email: j.gerritsen@erasmusmc.nl
• Study Contact Backup: Name: Arnaud Vincent, MD PhD; Phone Number: +31107034211; Email: a.vincent@erasmusmc.nl

Study Locations

• Belgium
  • Leuven, Belgium
    • Recruiting
    • University Hospital Leuven
    • Contact: Steven De Vleeschouwer, MD PhD
• Germany
  • Heidelberg, Germany
    • Recruiting
    • University Hospital Heidelberg
    • Contact: Christine Jungk, Dr. med.
  • Bavaria
    • Munich, Bavaria, Germany, 74076
      • Not yet recruiting
      • Technical University Munich
      • Contact: Arthur Wagner, MD PhD
• Netherlands
  • The Hague, Netherlands
    • Recruiting
    • Haaglanden Medical Center
    • Contact: Marike Broekman, MD PhD
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3015 GD
      • Recruiting
      • Erasmus Medical Center
      • Contact: Jasper Gerritsen, MD PhD
• Switzerland
  • Bern, Switzerland, 3010
    • Not yet recruiting
    • INSELSPITAL Universitätsspital Bern
    • Contact: Philippe Schucht, MD PhD
• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California, San Francisco
      • Contact: Mitchel Berger, MD PhD
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Brian Nahed, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• 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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Tumor resection	Procedure: Tumor resection; Maximal safe resection of the tumor
Tumor biopsy	Procedure: Tumor biopsy; Biopsy of the tumor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Time from diagnosis to death from any cause	Up to 5 years postoperatively
Adjuvant treatment with chemotherapy and radiotherapy	Proportion of patients that have received adjuvant treatment with chemotherapy and radiotherapy after surgery	6 months postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurological morbidity at 6 weeks	NIHSS deterioration of 1 point or more at 6 weeks after surgery	6 weeks postoperatively
Neurological morbidity at 3 months	NIHSS deterioration of 1 point or more at 3 months after surgery	3 months postoperatively
Neurological morbidity at 6 months	NIHSS deterioration of 1 point or more at 6 months after surgery	6 months postoperatively
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
Quality of life at 6 weeks (EORTC QLQ C30)	Quality of life as assessed by the EORTC QLQ C30 questionnaire	6 weeks postoperatively
Quality of life at 6 weeks (EORTC QLQ BN20)	Quality of life as assessed by the EORTC QLQ BN20 questionnaire	6 weeks postoperatively
Quality of life at 6 weeks (EQ-5D)	Quality of life as assessed by the EQ-5D questionnaire	6 weeks postoperatively
Quality of life at 3 months (EORTC QLQ C30)	Quality of life as assessed by the EORTC QLQ C30 questionnaire	3 months postoperatively
Quality of life at 3 months (EORTC QLQ BN20)	Quality of life as assessed by the EORTC QLQ BN20 questionnaire	3 months postoperatively
Quality of life at 3 months (EQ-5D)	Quality of life as assessed by the EQ-5D questionnaire	3 months postoperatively
Quality of life at 6 months (EORTC QLQ C30)	Quality of life as assessed by the EORTC QLQ C30 questionnaire	6 months postoperatively
Quality of life at 6 months (EORTC QLQ BN20)	Quality of life as assessed by the EORTC QLQ BN20 questionnaire	6 months postoperatively
Quality of life at 6 months (EQ-5D)	Quality of life as assessed by the EQ-5D questionnaire	6 months postoperatively
Serious Adverse Events	Serious Adverse Events within 6 weeks postoperatively	6 weeks postoperatively

Collaborators and Investigators

• Sponsor: Jasper Gerritsen
• Collaborators: Massachusetts General Hospital; Universitaire Ziekenhuizen KU Leuven; University of California, San Francisco; University Hospital Heidelberg; Technical University of Munich; Haaglanden Medical Centre; Insel Gruppe AG, University Hospital Bern
• Investigators: Principal Investigator: Jasper Gerritsen, MD PhD, Erasmus Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: November 18, 2023
• First Submitted That Met QC Criteria: November 18, 2023
• First Posted (Actual): November 27, 2023

Study Record Updates

• Last Update Posted (Actual): November 27, 2023
• Last Update Submitted That Met QC Criteria: November 18, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Survival; Quality of life; Biopsy; Resection
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: MEC-2020-0812-3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No