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

NCT ID: NCT02379572

Last Updated: 2021-10-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 315 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-30
• Study Completion Date: 2021-07-01

Brief Summary

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.

Conditions

Glioblastoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

iMRI-guided surgery

Resection of Glioblastomas with iMRI-guidance

Group Type: EXPERIMENTAL

iMRI-guided surgery

Intervention Type: DEVICE

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.

5-ALA-guided surgery

Resection of Glioblastomas with 5-ALA-fluorescence-guidance

Group Type: ACTIVE_COMPARATOR

5-ALA-guided surgery

Intervention Type: DRUG

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.

Interventions

iMRI-guided surgery

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.

Intervention Type: DEVICE

5-ALA-guided surgery

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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Tuebingen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Constantin Roder, Dr.

Role: PRINCIPAL_INVESTIGATOR

University Hospital Tuebingen, Department of Neurosurgery

Locations

Department of Neurosurgery, Universitätsklinikum Bonn, Bonn, Germany

Bonn, , Germany

Department of Neurosurgery, Universität zu Köln, Köln, Germany

Cologne, , Germany

Städtisches Klinikum Dresden Friedrichstadt

Dresden, , Germany

Department of Neurosurgery, Heinrich-Heine-Universität Düsseldorf, Düsseldorf

Düsseldorf, , Germany

Department of Neurosurgery, Friedrich-Alexander-University Erlangen-Nürnberg

Erlangen, , Germany

Department of Neurosurgery, Johann Wolfgang Goethe-University Frankfurt am Main

Frankfurt a.M., , Germany

Department of Neurosurgery, Georg-August-Universität Göttingen, Göttingen,

Göttingen, , Germany

Department of Neurosurgery, University of Ulm, Hospital Günzburg,

Günzburg, , Germany

Asklepios Klinik Hamburg, Klinik für Neurochirurgie

Hamburg, , Germany

International Neuroscience Institute Hannover, Hannover, Germany

Hanover, , Germany

Department of Neurosurgery, Ruprecht-Karls-University Heidelberg

Heidelberg, , Germany

Department of Neurosurgery, University of Schleswig-Holstein, Kiel, Germany

Kiel, , Germany

Department of Neurosurgery, Westfälische Wilhelms-Universität Münster, Münster, Germany

Münster, , Germany

Department of Neurosurgery, Eberhard Karls University, Tübingen,

Tübingen, , Germany

Department of Neurosurgery, Julius-Maximilians-Universität Würzburg

Würzburg, , Germany

Countries

Germany

References

Roder C, Stummer W, Coburger J, Scherer M, Haas P, von der Brelie C, Kamp MA, Lohr M, Hamisch CA, Skardelly M, Scholz T, Schipmann S, Rathert J, Brand CM, Pala A, Ernemann U, Stockhammer F, Gerlach R, Kremer P, Goldbrunner R, Ernestus RI, Sabel M, Rohde V, Tabatabai G, Martus P, Bisdas S, Ganslandt O, Unterberg A, Wirtz CR, Tatagiba M. Intraoperative MRI-Guided Resection Is Not Superior to 5-Aminolevulinic Acid Guidance in Newly Diagnosed Glioblastoma: A Prospective Controlled Multicenter Clinical Trial. J Clin Oncol. 2023 Dec 20;41(36):5512-5523. doi: 10.1200/JCO.22.01862. Epub 2023 Jun 19.

Reference Type: DERIVED

PMID: 37335962 (View on PubMed)

Other Identifiers

Nch1

Identifier Type: -

Identifier Source: org_study_id