Impact of iMRI on the Extent of Resection in Patients With Newly Diagnosed Glioblastomas

October 21, 2021 updated by: University Hospital Tuebingen

Impact of iMRI on the Extent of Resection in Patients With Newly Diagnosed Glioblastomas - A Prospective Multicenter Parallel Group Clinical Trial

Standard treatment of glioblastomas (GBMs) consists of microsurgical resection followed by concomitant chemoradiation. The extent of resection is one of the most important prognostic factors with significant influence on the survival of patients. State of the art technique to achieve the most radical resection possible in conventional surgery is fluorescence-guidance with 5-aminolevulinic acid (5-ALA). If available, intraoperative MRI (iMRI)-guided tumor resection enables an intraoperative resection control and subsequent continuation of surgery if contrast enhancing tumor remnants are found. Therefore a more radical resection and longer survival of patients might be possible. To date no comparison of these two leading technologies for GBM-surgery is available to identify the best surgical therapy of this fatal disease and to justify significant healthcare-economic differences between both technologies.

Goal of this study is to assess the value of iMRI guidance in the resection of GBMs in comparison to conventional 5-ALA microsurgery. Primary endpoint is the number of total resections (no residual contrast enhancement) in the postoperative MRI (T1+CM within 48 hours after surgery) in each group. Secondary endpoints are perioperative clinical data, progression free survival, patients' clinical condition and overall survival.

The study design was chosen to be a parallel-group approach to compare iMRI and 5-ALA centers (n=13) to exclude possible bias which might be found by randomizing patients within individual iMRI centers and to have surgeons with the most experience possible in use of each respective technology.

Study Overview

Status

Completed

Conditions

Study Type

Interventional

Enrollment (Actual)

315

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

      • Bonn, Germany
        • Department of Neurosurgery, Universitätsklinikum Bonn, Bonn, Germany
      • Cologne, Germany
        • Department of Neurosurgery, Universität zu Köln, Köln, Germany
      • Dresden, Germany
        • Städtisches Klinikum Dresden Friedrichstadt
      • Düsseldorf, Germany
        • Department of Neurosurgery, Heinrich-Heine-Universität Düsseldorf, Düsseldorf
      • Erlangen, Germany
        • Department of Neurosurgery, Friedrich-Alexander-University Erlangen-Nürnberg
      • Frankfurt a.M., Germany
        • Department of Neurosurgery, Johann Wolfgang Goethe-University Frankfurt am Main
      • Göttingen, Germany
        • Department of Neurosurgery, Georg-August-Universität Göttingen, Göttingen,
      • Günzburg, Germany
        • Department of Neurosurgery, University of Ulm, Hospital Günzburg,
      • Hamburg, Germany
        • Asklepios Klinik Hamburg, Klinik für Neurochirurgie
      • Hannover, Germany
        • International Neuroscience Institute Hannover, Hannover, Germany
      • Heidelberg, Germany
        • Department of Neurosurgery, Ruprecht-Karls-University Heidelberg
      • Kiel, Germany
        • Department of Neurosurgery, University of Schleswig-Holstein, Kiel, Germany
      • Münster, Germany
        • Department of Neurosurgery, Westfälische Wilhelms-Universität Münster, Münster, Germany
      • Tübingen, Germany
        • Department of Neurosurgery, Eberhard Karls University, Tübingen,
      • Würzburg, Germany
        • Department of Neurosurgery, Julius-Maximilians-Universität Würzburg

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 to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. In MRI suspected primary singular untreated GBM
  2. Planned total resection of the tumor according to the surgeon
  3. Patient ≥18 years, ≤80 years
  4. Preoperative KPS ≥ 60%, American Society of Anesthesiologists (ASA) score 1 and 2
  5. Patients' informed consent

Exclusion Criteria:

  1. Tumors of the midline, basal ganglia, cerebellum, brain stem, eloquent areas
  2. Multifocal glioblastoma
  3. Substantial (>50%), non-contrast enhancing tumor areas suggesting low-grade glioma with malignant transformation
  4. Contraindications to MRI
  5. Inability to give consent because of language barrier or dysphasia
  6. Histological diagnosis other than Glioblastoma multiforme WHO °IV
  7. Increased risk of thrombosis (e.g. Factor V Leiden)
  8. Pregnancy or breast feeding
  9. Hypersensibility for 5-ALA oder porphyrins
  10. Acute or chronic Porphyria
  11. Renal insufficiency
  12. Hepatic insufficiency
  13. High likelihood of inability to receive adjuvant therapy

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: iMRI-guided surgery
Resection of Glioblastomas with iMRI-guidance
For iMRI-guided glioma resections the surgery can be paused and a direct intraoperative resection control is possible by performing an intraoperative MRI scan. If residual tumor is found, the resection might be continued.
Active Comparator: 5-ALA-guided surgery
Resection of Glioblastomas with 5-ALA-fluorescence-guidance
For 5-ALA guided glioma resections patients have to drink 100ml of a solution with 5-Aminolevulinic acid 4-6 hours before surgery. Intraoperatively the light source of the surgical microscope can be switched to a certain wave length to enable fluorescence of the glioma cells, which helps resecting the tumor as radical as possible.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete resections in the postoperative MRI (T1+/-CM) within 48 hours after surgery
Time Frame: 48 hour
Completeness of resection in the postoperative MRI within 48h after surgery. Blinded analysis by an independent radiologist.
48 hour

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patients' clinical condition (KPS)
Time Frame: preoperative (day before surgery), 1 week, 3Months, 6Months, 9Months, 12Months after surgery
-KPS clinical scoring
preoperative (day before surgery), 1 week, 3Months, 6Months, 9Months, 12Months after surgery
Patients' clinical condition (NIHSS)
Time Frame: preoperative (day before surgery), 1 week, 3Months, 6Months, 9Months, 12Months after surgery
-NIHSS stroke score
preoperative (day before surgery), 1 week, 3Months, 6Months, 9Months, 12Months after surgery
Patients' clinical condition (QoL)
Time Frame: preoperative (day before surgery), 1 week, 3Months, 6Months, 9Months, 12Months after surgery
-quality of life (EORTC) questionnaire
preoperative (day before surgery), 1 week, 3Months, 6Months, 9Months, 12Months after surgery
ICU and hospital stay after surgery
Time Frame: Time of hospital stay (average 7days)
-ICU and overall hospital stay after surgery
Time of hospital stay (average 7days)
Patients' adjuvant treatment
Time Frame: 3Months, 6Months, 9Months, 12Months after surgery
-adjuvant treatment each patient has received
3Months, 6Months, 9Months, 12Months after surgery
Recurrent tumor growth (RANO criteria)
Time Frame: 3Months, 6Months, 9Months, 12Months after surgery
-recurrent tumor growth (RANO criteria) according to local tumor boards and independent blinded analysis
3Months, 6Months, 9Months, 12Months after surgery
Follow-up imaging
Time Frame: 3Months, 6Months, 9Months, 12Months after surgery
-follow-up imaging 3, 6, 9, 12 months postoperative incl. independent blinded analysis
3Months, 6Months, 9Months, 12Months after surgery
Histology
Time Frame: 1 week after surgery
Histological analysis
1 week after surgery
MGMT (O6-methylguanine-DNA-methyltransferase) analysis
Time Frame: 1 week after surgery
MGMT promoter analysis (Routine molecular diagnostics)
1 week after surgery
IDH-1 (isocitrate dehydrogenase) analysis
Time Frame: 1 week after surgery
IDH-1 mutation analysis (Routine molecular diagnostics)
1 week after surgery
Progression-free survival (PFS)
Time Frame: Day of surgery - 6 months - 12 months
6M&12M-PFS
Day of surgery - 6 months - 12 months
Overall survival (OS)
Time Frame: Day of surgery - Death of patient (Max. 10 years follow-up)
OS of patients
Day of surgery - Death of patient (Max. 10 years follow-up)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Preoperative tumor localization and resectability concerning eloquent regions
Time Frame: Blinded analysis of preoperative imaging (not older than 3 days prior to surgery)
Independent blinded analysis of the preoperative imaging data by a blinded neurosurgeon with extensive experience in the resection of gliomas. Analysis will be done before the final evaluation of results. (Within 12 months)
Blinded analysis of preoperative imaging (not older than 3 days prior to surgery)

Collaborators and Investigators

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

Investigators

  • Principal Investigator: Constantin Roder, Dr., University Hospital Tuebingen, Department of Neurosurgery

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

June 1, 2015

Primary Completion (Actual)

June 1, 2020

Study Completion (Actual)

July 1, 2021

Study Registration Dates

First Submitted

February 18, 2015

First Submitted That Met QC Criteria

February 26, 2015

First Posted (Estimate)

March 5, 2015

Study Record Updates

Last Update Posted (Actual)

October 22, 2021

Last Update Submitted That Met QC Criteria

October 21, 2021

Last Verified

July 1, 2020

More Information

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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