Surgery for Recurrent Glioblastoma (RESURGE)

July 17, 2023 updated by: Insel Gruppe AG, University Hospital Bern

RESURGE - Randomized Controlled Comparative Phase II Trial on Surgery for Glioblastoma Recurrence

Patients with glioblastoma face a grim prognosis. Despite recent advancement in neurosurgical technology and neuro-oncology glioblastomas almost invariably progress or recur after a median of 4-8 months. The strategy to repeat tumor resection at recurrence in order to minimize tumor load and thus to facilitate subsequent second-line therapy has been shown to be feasible and safe.

However, evidence for a survival benefit of surgery for recurrent glioblastoma is scarce and relies entirely on retrospective analyses. While most retrospective analyses report an apparent survival benefit, an EORTC meta-analysis on second-line therapies found no survival difference in patients with or without surgery at recurrence. With regard to the risks and costs inherent to surgery for glioblastoma, a randomized controlled trial is required.

The purpose of the study is to compare the effect of craniotomy and tumor resection followed by adjuvant second-line therapy to no surgery followed by second-line therapy on overall survival, neurological status, and quality of life. Analysis of overall survival will be used to improve sample size estimation of a subsequent phase III trial for craniotomy and tumor resection of glioblastoma recurrence in cooperation with the EORTC.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Background

Glioblastoma is a malignant, locally invasive brain tumor whose prognosis remains grim despite various intense treatment modalities. In the past, radical surgery was met with skepticism due to the aggressive infiltrative character of the tumor. However, an increasing number of retrospective studies over the last decade suggest a survival benefit for surgery. A recent post-hoc analysis of a randomized controlled trial on the use of the surgical adjunct 5-ALA reported a prolonged overall survival from 11.9 to 16.7 months (evidence level 2a) after more extensive resection. Thus, maximal safe resection has become a mainstay of treatment for newly diagnosed glioblastoma, followed by adjuvant radio-chemotherapy.

Glioblastoma almost invariably recurs after a median of 6.9 months, leaving but few options for further treatment. Recurrence of glioblastoma after surgery and concomitant adjuvant therapy represents an additional therapeutic challenge and may be treated with second-line pharmacotherapy. In addition, a second surgery may also be considered in highly selected patients.

The rationale for surgery - maximum safe resection - is to prolong survival through reduction of tumor load, and, maybe due to an increased efficacy of adjuvant treatment. However, surgery carries risks of complications, that may result in a decreased functional and survival outcome. The crucial question therefore is whether, to what extent, and at what costs in terms of neurological risks a second resection prolongs survival.

Objective

The primary objective of this randomized trial is to compare survival outcome after surgery followed by adjuvant second-line therapy to no surgery followed by second-line therapy in recurrent glioblastoma. An auxiliary objective to primary objective is to compare the survival outcomes of operated patients to control in the subgroups stratified by extent of resection: incomplete resection (non-CRET) vs complete resection (CRET).

Secondary objectives are: assessment of recruitment for all screened patients, comparison of progression-free survival between treatment arms, evaluation of crossover and comparison of patient quality of life between treatment arms.

Safety objectives are: to assess neurological deficits, local infections and morbidity associated to surgery and hospital stay after surgery and during follow-up.

Methods

All patients (≥18 years) with a radiological suspicion of first recurrence of glioblastoma are screened for this trial. Patients eligible for study participation are informed on the treatment options for recurrent glioblastoma (surgery followed by adjuvant second-line therapy, second-line therapy, or palliative therapy alone) by the center investigators. Patients randomized to the control group will receive second-line therapy according to local guidelines. Patients randomized to the interventional group will receive a craniotomy and resection of the tumor followed by adjuvant second-line therapy. Outcome will be measured at 3 months intervals.

Recruitment rate and reason for non-inclusion will be monitored.

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Austria
  • Germany
      • Erfurt, Germany, 99089
      • Frankfurt, Germany, 60590
        • Recruiting
        • Department of Neurosurgery, Universitätsklinikum Frankfurt
        • Contact:
          • Forster Marie-Thérèse, MD
      • Freiburg, Germany, 79106
        • Recruiting
        • Dep. of Neurosurgery, Universitätsklinikum Freiburg
        • Contact:
          • Schnell Oliver, MD
      • Giessen, Germany, 35392
      • Köln, Germany, 50937
        • Recruiting
        • Department of Neurosurgery, Universitätsklinikum Köln
        • Contact:
          • Boris Krischek, MD
      • Mainz, Germany
        • Recruiting
        • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
        • Contact:
          • Naureen Keric, MD
      • Münster, Germany, 48149
  • Greece
      • Larissa, Greece, 412 21
        • Recruiting
        • Department of Neurosurgery, Hospital of Larissa & General Hospital of Larissa
        • Contact:
          • Kostas Fountas, MD
      • Thessaloníki, Greece, 546 21
        • Recruiting
        • Department of Neurosurgery, AHEPA University Hospital
        • Contact:
          • Nicolas Foroglou, MD
  • Italy
  • Portugal
      • Lisboa, Portugal, 1649-035
        • Recruiting
        • Department of Neurosurgery, Centro Hospitalar Universitário Lisboa Norte - Hospital de Santa Maria
        • Contact:
          • Alexandre Rainha Campos, MD
  • Romania
      • Bucharest, Romania, 041915
        • Recruiting
        • Department of Neurosurgery, Spitalul Clinic De Urgență "Bagdasar-Arseni"
        • Contact:
          • George Petrescu, MD
  • Switzerland
      • Aarau, Switzerland, 5001
        • Recruiting
        • Kantonsspital Aarau
        • Contact:
      • Basel, Switzerland, 4031
      • Bern, Switzerland, 3010
        • Recruiting
        • Dep. of Neurosurgery, Bern University Hospital
        • Principal Investigator:
          • Philippe Schucht
      • Geneva, Switzerland, 1205
        • Recruiting
        • Dep. of Neurosurger, Hôpitaux Universitaires de Genève
        • Principal Investigator:
          • Torstein Mehling
      • Lausanne, Switzerland, 1011
        • Recruiting
        • Dep. of Neurosurgery, Centre hospitalier universitaire vaudois
        • Principal Investigator:
          • Andreas Hottinger
      • Lugano, Switzerland, 6900
      • Luzern, Switzerland, 6000
      • Saint Gallen, Switzerland, 9007
        • Recruiting
        • Department of Neurosurgery, Kantonsspital St. Gallen
        • Contact:
          • Evangelos Kogias, MD
      • Zurich, Switzerland, 8091
        • Recruiting
        • Dep. of Neurosurgery, University Hospital of Zurich
        • Principal Investigator:
          • Luca Regli

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Written informed consent
  • ≥18 years of age
  • Prior resection of glioblastoma confirmed by histology
  • Glioblastoma pretreated with standard radiotherapy without or with temozolomide
  • First progression according to RANO criteria
  • First progression not within 3 months after completion of radiation therapy
  • Complete removal of contrast-enhancing lesion considered feasible without significant risk of permanent speech or motor function according to MRI as confirmed by study eligibility committee after screening and prior to recruitment
  • No encroachment of the M1 or A1 segments of the medial and anterior cerebral artery on MRI
  • No contrast enhancement in presumed speech and primary motor areas on MRI
  • No midline shift on MRI
  • No contrast enhancing ventricular spread, multifocal recurrence, meningeosis carcinomatosa or infiltration of the contra-lateral hemisphere on MRI
  • No contra-indication for surgery
  • Good functional status (KPS ≥ 70)

Exclusion Criteria

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Surgery followed by adjuvant second-line therapy
Procedure: Surgery followed by adjuvant second-line therapy

Surgery:

Surgery must take place between day 1 and 14 after study inclusion and within 21 days from the MRI on which recurrence was diagnosed. The modalities of surgery and the choice of pre- and intra-operative technical adjuncts is at the treating neurosurgery discretion. Surgery must take place between day 1 and 14 after study inclusion and within 21 days from the MRI on which recurrence was diagnosed. The modalities of surgery and the choice of pre- and intra-operative technical adjuncts is at the treating neurosurgery discretion. However, some form of intra-operative resection control (iMRI or intra-operative fluorescence) and function control (electrophysiology) should be available to the surgeon and used when warranted.

Adjuvant second-line therapy:

Patients will be seen after surgery by the treating neurooncologist. Modalities of adjuvant second-line therapy are individually defined according to local guidelines and are not stipulated by study protocol.
Active Comparator: Second-line therapy alone
Procedure: Second-line therapy alone
Patients randomized to the non-surgical cohort receive second-line therapy according to local guidelines. Modalities thereof are not stipulated by study protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Overall survival from the date of inclusion
Time Frame: From the date of inclusion until death/end of study, assessed up to 5.7 years
From the date of inclusion until death/end of study, assessed up to 5.7 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Recruitment rate for all screened patients
Time Frame: Screening and inclusion
Screening and inclusion
Progression-free survival
Time Frame: From the date of inclusion until the date of objective progression or the date of patient's death, whichever occurs first, assessed up to 5.7 years
From the date of inclusion until the date of objective progression or the date of patient's death, whichever occurs first, assessed up to 5.7 years
Morbidity of surgery
Time Frame: Every 3 months up to 2 years or until death, assessed up to 5.7 years
Every 3 months up to 2 years or until death, assessed up to 5.7 years
Total number of days spent at home after recurrence
Time Frame: From the date of inclusion until death/end of study, assessed up to 5.7 years
From the date of inclusion until death/end of study, assessed up to 5.7 years
Total number of days spent outside home after recurrence
Time Frame: From the date of inclusion until death/end of study, assessed up to 5.7 years
From the date of inclusion until death/end of study, assessed up to 5.7 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Insel Gruppe AG, University Hospital Bern

Collaborators

European Organisation for Research and Treatment of Cancer - EORTC

Investigators

  • Principal Investigator: Philippe Schucht, Prof. Dr. med., Dep. of Neurosurgery, Inselspital Bern

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2015

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

March 11, 2015

First Submitted That Met QC Criteria

March 19, 2015

First Posted (Estimated)

March 20, 2015

Study Record Updates

Last Update Posted (Actual)

July 18, 2023

Last Update Submitted That Met QC Criteria

July 17, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 368/14

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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