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

Glioblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02379572
• Other study ID #: Nch1
• Status: Completed
• Phase: N/A
• Start date: June 2015
• Est. completion date: July 1, 2021

Study information

• Verified date: July 2020
• Source: University Hospital Tuebingen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 315
• Est. completion date: July 1, 2021
• Est. primary completion date: June 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Glioblastoma

Intervention

Device:
• 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.

Drug:
• 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.

Locations

Country	Name	City	State
Germany	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	Hannover
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

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Tuebingen

Country where clinical trial is conducted

Germany, 

Outcome

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