Clinical trial NCT02379572: Impact of iMRI on the Extent of Resection in Patients With Newly Diagnosed Glioblastomas
Official title: Impact of iMRI on the Extent of Resection in Patients With Newly Diagnosed Glioblastomas - A Prospective Multicenter Parallel Group Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Glioblastoma
Keywords: 5-ALA
Intraoperative MRI
Extent of resection
Lead sponsor: University Hospital Tuebingen
Sponsor class: OTHER
First posted: 2015-03-05
Enrollment: 315
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Complete resections in the postoperative MRI (T1+/-CM) within 48 hours after surgery
timeFrame: 48 hour
Secondary outcomes:
measure: Patients' clinical condition (KPS)
timeFrame: preoperative (day before surgery), 1 week, 3Months, 6Months, 9Months, 12Months after surgery
measure: Patients' clinical condition (NIHSS)
timeFrame: preoperative (day before surgery), 1 week, 3Months, 6Months, 9Months, 12Months after surgery
measure: Patients' clinical condition (QoL)
timeFrame: preoperative (day before surgery), 1 week, 3Months, 6Months, 9Months, 12Months after surgery
measure: ICU and hospital stay after surgery
timeFrame: Time of hospital stay (average 7days)
measure: Patients' adjuvant treatment
timeFrame: 3Months, 6Months, 9Months, 12Months after surgery
measure: Recurrent tumor growth (RANO criteria)
timeFrame: 3Months, 6Months, 9Months, 12Months after surgery
measure: Follow-up imaging
timeFrame: 3Months, 6Months, 9Months, 12Months after surgery
measure: Histology
timeFrame: 1 week after surgery
measure: MGMT (O6-methylguanine-DNA-methyltransferase) analysis
timeFrame: 1 week after surgery
measure: IDH-1 (isocitrate dehydrogenase) analysis
timeFrame: 1 week after surgery
measure: Progression-free survival (PFS)
timeFrame: Day of surgery - 6 months - 12 months
measure: Overall survival (OS)
timeFrame: Day of surgery - Death of patient (Max. 10 years follow-up)
Other outcomes:
measure: Preoperative tumor localization and resectability concerning eloquent regions
timeFrame: Blinded analysis of preoperative imaging (not older than 3 days prior to surgery)
Locations:
city: Bonn
country: Germany
facility: Department of Neurosurgery, Universitätsklinikum Bonn, Bonn, Germany
city: Cologne
country: Germany
facility: Department of Neurosurgery, Universität zu Köln, Köln, Germany
city: Dresden
country: Germany
facility: Städtisches Klinikum Dresden Friedrichstadt
city: Düsseldorf
country: Germany
facility: Department of Neurosurgery, Heinrich-Heine-Universität Düsseldorf, Düsseldorf
city: Erlangen
country: Germany
facility: Department of Neurosurgery, Friedrich-Alexander-University Erlangen-Nürnberg
city: Frankfurt a.M.
country: Germany
facility: Department of Neurosurgery, Johann Wolfgang Goethe-University Frankfurt am Main
city: Göttingen
country: Germany
facility: Department of Neurosurgery, Georg-August-Universität Göttingen, Göttingen,
city: Günzburg
country: Germany
facility: Department of Neurosurgery, University of Ulm, Hospital Günzburg,
city: Hamburg
country: Germany
facility: Asklepios Klinik Hamburg, Klinik für Neurochirurgie
city: Hannover
country: Germany
facility: International Neuroscience Institute Hannover, Hannover, Germany
city: Heidelberg
country: Germany
facility: Department of Neurosurgery, Ruprecht-Karls-University Heidelberg
city: Kiel
country: Germany
facility: Department of Neurosurgery, University of Schleswig-Holstein, Kiel, Germany
city: Münster
country: Germany
facility: Department of Neurosurgery, Westfälische Wilhelms-Universität Münster, Münster, Germany
city: Tübingen
country: Germany
facility: Department of Neurosurgery, Eberhard Karls University, Tübingen,
city: Würzburg
country: Germany
facility: Department of Neurosurgery, Julius-Maximilians-Universität Würzburg
Study officials:
affiliation: University Hospital Tuebingen, Department of Neurosurgery
name: Constantin Roder, Dr.
role: PRINCIPAL_INVESTIGATOR
References: