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

Not Applicable

Completed

• Conditions: Glioblastoma
• Interventions: Device: iMRI-guided surgery; Drug: 5-ALA-guided surgery

• Registration Number: NCT02379572
• Lead Sponsor: University Hospital Tuebingen

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-02-18
• Study First Submitted QC: 2015-02-26
• Study First Posted: 2015-03-05
• Study Start: 2015-06
• Primary Completion: 2020-06
• Status Verified: 2020-07
• Study Completion: 2021-07-01
• Last Update Submitted: 2021-10-21
• Last Update Posted: 2021-10-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 315

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
iMRI-guided surgery	iMRI-guided surgery	Resection of Glioblastomas with iMRI-guidance
5-ALA-guided surgery	5-ALA-guided surgery	Resection of Glioblastomas with 5-ALA-fluorescence-guidance

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (15)

International Neuroscience Institute Hannover, Hannover, Germany; 🇩🇪 Hannover, Germany

Department of Neurosurgery, Friedrich-Alexander-University Erlangen-Nürnberg; 🇩🇪 Erlangen, Germany

Department of Neurosurgery, University of Ulm, Hospital Günzburg,; 🇩🇪 Günzburg, Germany

Department of Neurosurgery, Georg-August-Universität Göttingen, Göttingen,; 🇩🇪 Göttingen, Germany

Department of Neurosurgery, Universität zu Köln, Köln, Germany; 🇩🇪 Cologne, Germany

Department of Neurosurgery, Ruprecht-Karls-University Heidelberg; 🇩🇪 Heidelberg, Germany

Department of Neurosurgery, University of Schleswig-Holstein, Kiel, Germany; 🇩🇪 Kiel, Germany

Städtisches Klinikum Dresden Friedrichstadt; 🇩🇪 Dresden, Germany

Department of Neurosurgery, Julius-Maximilians-Universität Würzburg; 🇩🇪 Würzburg, Germany

Department of Neurosurgery, Universitätsklinikum Bonn, Bonn, Germany; 🇩🇪 Bonn, Germany

Department of Neurosurgery, Johann Wolfgang Goethe-University Frankfurt am Main; 🇩🇪 Frankfurt a.M., Germany

Department of Neurosurgery, Westfälische Wilhelms-Universität Münster, Münster, Germany; 🇩🇪 Münster, Germany

Department of Neurosurgery, Eberhard Karls University, Tübingen,; 🇩🇪 Tübingen, Germany

Department of Neurosurgery, Heinrich-Heine-Universität Düsseldorf, Düsseldorf; 🇩🇪 Düsseldorf, Germany

Asklepios Klinik Hamburg, Klinik für Neurochirurgie; 🇩🇪 Hamburg, Germany