Surgery for Recurrent Glioblastoma

NCT ID: NCT02394626

Last Updated: 2026-02-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-05-01

Study Completion Date

2028-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Glioblastoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Second-line therapy alone

Second-line therapy alone

Group Type ACTIVE_COMPARATOR

Second-line therapy alone

Intervention Type PROCEDURE

Patients randomized to the non-surgical cohort receive second-line therapy according to local guidelines. Modalities thereof are not stipulated by study protocol.

Surgery followed by adjuvant second-line therapy

Surgery followed by adjuvant second-line therapy

Group Type EXPERIMENTAL

Surgery followed by adjuvant second-line therapy

Intervention Type PROCEDURE

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type 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.

Intervention Type PROCEDURE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role collaborator

Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Philippe Schucht, Prof. Dr. med.

Role: PRINCIPAL_INVESTIGATOR

Dep. of Neurosurgery, Inselspital Bern

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Universitätsklinikum Innsbruck

Innsbruck, , Austria

Site Status RECRUITING

Johannes Kepler University Linz University, Clinic for Neurosurgery

Linz, , Austria

Site Status RECRUITING

Medical University of Vienna, Department of Neurosurgery

Vienna, , Austria

Site Status RECRUITING

Centre Hospitalier Universitaire Dijon Bourgogne, Department of Neurosurgery

Dijon, , France

Site Status RECRUITING

Hospices Civils de Lyon - CHU de Lyon, Department of Neuro-Oncology

Lyon, , France

Site Status RECRUITING

Assistance Publique - Hôpitaux de Marseille, Department of Neuro-Oncology

Marseille, , France

Site Status RECRUITING

Centre Hospitalier Universitaire de Nice, Department of Neurosurgery

Nice, , France

Site Status RECRUITING

Assistance Publique - Hôpitaux de Paris (AP-HP), Department of Neurosurgery

Paris, , France

Site Status RECRUITING

Centre Hospitalier Universitaire de Saint-Étienne, Department of Neurosurgery

Saint-Etienne, , France

Site Status RECRUITING

Institut de Cancérologie Strasbourg Europe (ICANS), Department of Oncology

Strasbourg, , France

Site Status RECRUITING

Centre Hospitalier Régional et Universitaire de Tours (CHRU Tours), Department of Neurosurgery

Tours, , France

Site Status RECRUITING

Helios Klinikum Erfurt

Erfurt, , Germany

Site Status RECRUITING

Universitätsklinikum Münster

Münster, , Germany

Site Status RECRUITING

Department of Neurosurgery, Hospital of Larissa & General Hospital of Larissa

Larissa, , Greece

Site Status RECRUITING

Department of Neurosurgery, Amsterdam University Medical Center

Amsterdam, , Netherlands

Site Status RECRUITING

Department of Neurosurgery, Radboud University Medical Center, Nijmegen

Nijmegen, , Netherlands

Site Status RECRUITING

Department of Neurosurgery, Haaglanden Medical Center, The Hague

The Hague, , Netherlands

Site Status RECRUITING

Department of Neurosurgery, Centro Hospitalar Universitário Lisboa Norte - Hospital de Santa Maria

Lisbon, , Portugal

Site Status RECRUITING

Department of Neurosurgery, L'Hospitalet de Llobregat, Barcelona

Barcelona, , Spain

Site Status RECRUITING

University of Gothenburg, Department of Clinical Neuroscience

Gothenburg, , Sweden

Site Status NOT_YET_RECRUITING

University Hospital of Umeå, Department of Diagnostics and Intervention

Umeå, , Sweden

Site Status NOT_YET_RECRUITING

Universitätsspital Basel

Basel, , Switzerland

Site Status RECRUITING

Dep. of Neurosurgery, Bern University Hospital

Bern, , Switzerland

Site Status RECRUITING

Dep. of Neurosurgery, Centre hospitalier universitaire vaudois

Lausanne, , Switzerland

Site Status RECRUITING

Ospedale Regionale di Lugano

Lugano, , Switzerland

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Austria France Germany Greece Netherlands Portugal Spain Sweden Switzerland

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Philippe Schucht, MD

Role: CONTACT

+41 31 66 4 28 65

David Hasler

Role: CONTACT

+41 31 632 76 80

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Christian Freyschlag, MD

Role: primary

Johannes Kerschbaumer, MD

Role: backup

Andreas Gruber

Role: primary

+43 732 2468 0

Barbara Kiesel, MD

Role: primary

+43 1 40400-45650

Tuan Le Van

Role: primary

+33 380293752

Francois Ducray

Role: primary

+33478866634

Emeline Tabouret

Role: primary

+33 4 91 38 55 00

Fabien Almairac

Role: primary

+33492038450

Bertrand Mathon

Role: primary

+33 1 40 27 30 00

Fanélie Barral-Clavel

Role: primary

+33 4 77 82 80 00

Georges Noel

Role: primary

+33 3 68 76 67 67

Ilyess Zemmoura

Role: primary

+33 2 47 47 47 47

Rüdiger Gerlach, MD

Role: primary

Benjamin Brokinkel

Role: primary

Kostas Fountas, MD

Role: primary

Philip de Witt Hamer, MD

Role: primary

Mark ter Laan, MD

Role: primary

Marike Broekman, MD

Role: primary

Alexandre Rainha Campos, MD

Role: primary

Gerard Plans, MD

Role: primary

Jakola Asgeir

Role: primary

+46 31-786 00 00

Maria Sandström

Role: primary

+46 90 785 00 00

Dominik Cordier

Role: primary

Andreas Hottinger, MD

Role: primary

Francesco Marchi, MD

Role: primary

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

368/14

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.