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

NCT02379572 | Completed DMC

• 1 other identifier: Nch1
• Study Type: interventional
• Target: 315
• Locations: 1 country
• Sites: 15

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

Keywords

5-ALA; Intraoperative MRI; Extent of resection

Outcome Measures

Primary Outcomes (1)

• Complete resections in the postoperative MRI (T1+/-CM) within 48 hours after surgery

  Completeness of resection in the postoperative MRI within 48h after surgery. Blinded analysis by an independent radiologist.

  48 hour

Secondary Outcomes (12)

• Patients' clinical condition (KPS)

  preoperative (day before surgery), 1 week, 3Months, 6Months, 9Months, 12Months after surgery

• Patients' clinical condition (NIHSS)

  preoperative (day before surgery), 1 week, 3Months, 6Months, 9Months, 12Months after surgery

• Patients' clinical condition (QoL)

  preoperative (day before surgery), 1 week, 3Months, 6Months, 9Months, 12Months after surgery

• ICU and hospital stay after surgery

  Time of hospital stay (average 7days)

• Patients' adjuvant treatment

  3Months, 6Months, 9Months, 12Months after surgery

Other Outcomes (1)

• Preoperative tumor localization and resectability concerning eloquent regions

  Blinded analysis of preoperative imaging (not older than 3 days prior to surgery)

Study Arms (2)

iMRI-guided surgery

EXPERIMENTAL

Resection of Glioblastomas with iMRI-guidance

Device: iMRI-guided surgery

5-ALA-guided surgery

ACTIVE COMPARATOR

Resection of Glioblastomas with 5-ALA-fluorescence-guidance

Drug: 5-ALA-guided surgery

Interventions

iMRI-guided surgery 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.

iMRI-guided surgery

5-ALA-guided surgery 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.

5-ALA-guided surgery

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (15)

Department of Neurosurgery, Universitätsklinikum Bonn, Bonn, Germany

Bonn, Germany

Location

Department of Neurosurgery, Universität zu Köln, Köln, Germany

Cologne, Germany

Location

Städtisches Klinikum Dresden Friedrichstadt

Dresden, Germany

Location

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

Düsseldorf, Germany

Location

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

Erlangen, Germany

Location

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

Frankfurt a.M., Germany

Location

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

Göttingen, Germany

Location

Department of Neurosurgery, University of Ulm, Hospital Günzburg,

Günzburg, Germany

Location

Asklepios Klinik Hamburg, Klinik für Neurochirurgie

Hamburg, Germany

Location

International Neuroscience Institute Hannover, Hannover, Germany

Hanover, Germany

Location

Department of Neurosurgery, Ruprecht-Karls-University Heidelberg

Heidelberg, Germany

Location

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

Kiel, Germany

Location

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

Münster, Germany

Location

Department of Neurosurgery, Eberhard Karls University, Tübingen,

Tübingen, Germany

Location

Department of Neurosurgery, Julius-Maximilians-Universität Würzburg

Würzburg, Germany

Location

Related Publications (1)

• 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.

  PMID: 37335962 DERIVED

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Constantin Roder, Dr.

  University Hospital Tuebingen, Department of Neurosurgery

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2015
• First Posted: March 5, 2015
• Study Start: June 1, 2015
• Primary Completion: June 1, 2020
• Study Completion: July 1, 2021
• Last Updated: October 22, 2021

Record last verified: 2020-07

Locations

DE (15)