Role of Repeat Resection in Recurrent Glioblastoma

July 2, 2025 updated by: University of Alberta

Role of Repeat Resection in Recurrent Glioblastoma (4rGBM) Trial: a Randomized Care Trial for Patients With Recurrent GBM

Patients with recurrent Glioblastoma (GBM) are commonly presented to surgeons, along with the question of whether or not to re-resect the recurrence. There is no Level 1 evidence to support a role for repeat surgery in this context, but a multitude of observational research suggests that repeat surgery may improve quality survival. Unfortunately, these studies all suffer from selection bias.

The goal of this study is to provide a care trial context to help neurosurgeons manage patients presenting with recurrent GBM, with no additional risks, tests, or interventions than what they would normally encounter in routine care. Secondary goals include a test of the hypothesis that repeat resection can improve median overall survival, and that it can increase the number of days of survival outside of a hospital/nursing/palliative care facility.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Glioblastoma (GBM) is the most common malignant brain tumor (48.3% of malignant tumors).1 It has a predilection for Caucasian men with a mean age of 65.1, 2 There are approximately 13,000 new diagnoses of GBM made every year in the United States.1 Patients have an average survival of 12-15 months, with a 5-year survival rate of 6.8% despite various treatments.1 If the prognosis at the time of initial diagnosis is grim, it is even worse at the time of recurrence. Recurrence after the initial resection, which can be symptomatic or discovered on surveillance MRI imaging, occurs in nearly all patients, usually within the first year, even when the initial management is aggressive.3-6 There is no standard way to care for recurrent GBM patients and treatment may include one or more of the following: repeat surgery, radiation therapy, or second-line chemotherapy.7

Repeat surgical management carries a greater risk of wound infection and cerebrospinal fluid leak than the initial surgery, especially in patients who received radiation.8 When maximal resection was attempted at the time of the initial procedure, the second surgery is more at risk of neurological injury. Repeat surgical management often also entails a delay in the initiation of further chemotherapy, as these agents are not administered peri-operatively because of potentially deleterious effects on wound healing. Nonetheless, despite, or because of the desperate setting, patients and surgeons are often pressed to consider repeat surgery, which is performed in at least 10-30% of patients.9 Repeat surgical treatment may be more favorable with younger age (<60 years), and preoperative Karnofsky performance status (KPS) of at least 70.9 Median survival following repeat resection varies between 13-54 weeks,10, 11 but all reports suffer from the limitations of retrospective studies, the most obvious being selection bias in terms of patient age, functional status, tumor location and size.11, 12 Yet, despite favorable biases some studies report no improvement in terms of survival or quality of life.13, 14 Two recent systematic meta-analyses of case series offer conflicting conclusions about the merit of re-operation.15, 16

If the intent of repeat surgery is to improve quality and quantity of life, there is no level 1 evidence it is effective.3, 16, 17 Thus repeat surgery should be considered the experimental arm of a randomized trial designed in the best interest of the patient, being only offered as a 50% chance, always balanced by a 50% chance of being allocated non-surgical care, or a chance to escape what could turn out to be unnecessary or harmful surgery.18 For patients may be better served by being free to pursue other life priorities in the company of loved ones rather than being scheduled to endure repeat craniotomy and multiple clinical or research follow-up visits. There is sufficient community equipoise to support the conduct of such a randomized trial.19

Tria Design:

The trial is a simple, all-inclusive, prospective, multicenter, randomized care trial18 that allocates 1:1 re-operation (or not) for patients with recurrent Glioblastoma. The primary outcome is overall survival. Secondary outcomes include standard peri-operative safety outcomes and (a notion of) 'quality survival', or survival at home, measured by counting days of survival minus days in hospital/nursing home/palliative care setting. Blinding is not feasible; treatment allocation will not be masked. The trial allows for pre-randomization.22 The burden of the proof of benefit is on surgery. While some patients allocated non-surgical management may still want surgery, and some patients allocated surgery may prefer non-surgical management, we feel participating patients will be better informed by the discussion around trial participation.

Hypothesis:

Patients with recurrent Glioblastoma, at the time they are considered for repeat resection, who undergo repeat resection for the GBM, will experience an increase in median overall survival from 6 to 9 months.

Study Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

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

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 2B7
        • University of Alberta Division of Neurosurgery

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:

  • Age ≥ 18
  • Previously histologically confirmed and surgically resected Glioblastoma
  • Previous craniotomy for open tumor resection (needle biopsies alone do not count as resection)
  • The attending surgeon considers re-operation may improve quality survival

Exclusion Criteria:

  • Informed consent not possible

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: Repeat Surgical Resection
Standard surgical operative management according to local practices.
Procedure: Repeat Surgical Management of Recurrent GBM
Routine of surgical operative management. Details of treatment will be left to local centers, and recorded in the case report form (CRF).
Active Comparator: Management Without Re-operation
Non-surgical management with standard care according to local practices.
Procedure: Repeat Surgical Management of Recurrent GBM
Routine of surgical operative management. Details of treatment will be left to local centers, and recorded in the case report form (CRF).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Length of Overall Survival
Time Frame: Follow-up for 5 Years or until death
The primary outcome is time to death from any cause, starting from the time of inclusion.
Follow-up for 5 Years or until death

Secondary Outcome Measures

Outcome Measure
Time Frame
Total length of hospitalization / palliative care / nursing home
Time Frame: Follow-up for 5 Years or until death
Follow-up for 5 Years or until death
Discharge to a location other than home
Time Frame: Follow-up for 5 Years or until death
Follow-up for 5 Years or until death
Total number of days spent outside a hospital or nursing care facility.
Time Frame: Follow-up for 5 Years or until death
Follow-up for 5 Years or until death
Incidence of peri-operative non-neurological complications (wound infection, CSF leaks)
Time Frame: Follow-up for 5 Years or until death
Follow-up for 5 Years or until death
Incidence of new significant neurological deficits after surgery (defined as new or substantially worsened aphasia, or new weakness (MRC power < 3 in one or more limbs).
Time Frame: Follow-up for 5 Years or until death
Follow-up for 5 Years or until death

Collaborators and Investigators

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

Sponsor

University of Alberta

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

August 26, 2021

Primary Completion (Actual)

March 24, 2025

Study Completion (Actual)

March 24, 2025

Study Registration Dates

First Submitted

April 4, 2021

First Submitted That Met QC Criteria

April 6, 2021

First Posted (Actual)

April 9, 2021

Study Record Updates

Last Update Posted (Estimated)

July 8, 2025

Last Update Submitted That Met QC Criteria

July 2, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CC-210049

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data will be made available upon reasonable request.

IPD Sharing Time Frame

Indefinitely

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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