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

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ClinicalTrials.gov Identifier: NCT02379572
Recruitment Status : Recruiting
First Posted : March 5, 2015
Last Update Posted : June 13, 2018
Sponsor:
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Glioblastoma Device: iMRI-guided surgery Drug: 5-ALA-guided surgery Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 276 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Impact of iMRI on the Extent of Resection in Patients With Newly Diagnosed Glioblastomas - A Prospective Multicenter Parallel Group Clinical Trial
Study Start Date : June 2015
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018


Arm Intervention/treatment
Experimental: iMRI-guided surgery
Resection of Glioblastomas with iMRI-guidance
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.

Active Comparator: 5-ALA-guided surgery
Resection of Glioblastomas with 5-ALA-fluorescence-guidance
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.




Primary Outcome Measures :
  1. Complete resections in the postoperative MRI (T1+/-CM) within 48 hours after surgery [ Time Frame: 48 hour ]
    Completeness of resection in the postoperative MRI within 48h after surgery. Blinded analysis by an independent radiologist.


Secondary Outcome Measures :
  1. Patients' clinical condition (KPS) [ Time Frame: preoperative (day before surgery), 1 week, 3Months, 6Months, 9Months, 12Months after surgery ]
    -KPS clinical scoring

  2. Patients' clinical condition (NIHSS) [ Time Frame: preoperative (day before surgery), 1 week, 3Months, 6Months, 9Months, 12Months after surgery ]
    -NIHSS stroke score

  3. Patients' clinical condition (QoL) [ Time Frame: preoperative (day before surgery), 1 week, 3Months, 6Months, 9Months, 12Months after surgery ]
    -quality of life (EORTC) questionnaire

  4. ICU and hospital stay after surgery [ Time Frame: Time of hospital stay (average 7days) ]
    -ICU and overall hospital stay after surgery

  5. Patients' adjuvant treatment [ Time Frame: 3Months, 6Months, 9Months, 12Months after surgery ]
    -adjuvant treatment each patient has received

  6. Recurrent tumor growth (RANO criteria) [ Time Frame: 3Months, 6Months, 9Months, 12Months after surgery ]
    -recurrent tumor growth (RANO criteria) according to local tumor boards and independent blinded analysis

  7. Follow-up imaging [ Time Frame: 3Months, 6Months, 9Months, 12Months after surgery ]
    -follow-up imaging 3, 6, 9, 12 months postoperative incl. independent blinded analysis

  8. Histology [ Time Frame: 1 week after surgery ]
    Histological analysis

  9. MGMT (O6-methylguanine-DNA-methyltransferase) analysis [ Time Frame: 1 week after surgery ]
    MGMT promoter analysis (Routine molecular diagnostics)

  10. IDH-1 (isocitrate dehydrogenase) analysis [ Time Frame: 1 week after surgery ]
    IDH-1 mutation analysis (Routine molecular diagnostics)

  11. Progression-free survival (PFS) [ Time Frame: Day of surgery - 6 months - 12 months ]
    6M&12M-PFS

  12. Overall survival (OS) [ Time Frame: Day of surgery - Death of patient (Max. 10 years follow-up) ]
    OS of patients


Other Outcome Measures:
  1. Preoperative tumor localization and resectability concerning eloquent regions [ Time Frame: Blinded analysis of preoperative imaging (not older than 3 days prior to surgery) ]
    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)



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02379572


Contacts
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Contact: Constantin Roder, Dr. +4970712980325 constantin.roder@uni-tuebingen.de
Contact: Manola Zago, Dr. +49 7071 29 85629 manola.zago@med.uni-tuebingen.de

Locations
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Germany
Department of Neurosurgery, Universitätsklinikum Bonn, Bonn, Germany Recruiting
Bonn, Germany
Contact: Hartmut Vatter         
Department of Neurosurgery, Universität zu Köln, Köln, Germany Recruiting
Cologne, Germany
Contact: Roland Goldbrunner, Prof. Dr.         
Städtisches Klinikum Dresden Friedrichstadt Recruiting
Dresden, Germany
Contact: Florian Stockhammer, Prof. Dr.         
Department of Neurosurgery, Heinrich-Heine-Universität Düsseldorf, Düsseldorf Recruiting
Düsseldorf, Germany
Contact: Michael Sabel, Prof. Dr.         
Department of Neurosurgery, Friedrich-Alexander-University Erlangen-Nürnberg Recruiting
Erlangen, Germany
Contact: Andreas Merkel, Dr.         
Department of Neurosurgery, Johann Wolfgang Goethe-University Frankfurt am Main Not yet recruiting
Frankfurt a.M., Germany
Contact: Christian Senft, Prof. Dr.         
Department of Neurosurgery, Georg-August-Universität Göttingen, Göttingen, Recruiting
Göttingen, Germany
Contact: Florian Stockhammer, PD Dr.         
Department of Neurosurgery, University of Ulm, Hospital Günzburg, Recruiting
Günzburg, Germany
Contact: Jan Coburger, Dr.         
Asklepios Klinik Hamburg, Klinik für Neurochirurgie Recruiting
Hamburg, Germany
Contact: Paul Kremer, Prof. Dr.         
International Neuroscience Institute Hannover, Hannover, Germany Not yet recruiting
Hannover, Germany
Contact: Mario Giordano, Dr.         
Department of Neurosurgery, Ruprecht-Karls-University Heidelberg Recruiting
Heidelberg, Germany
Contact: Moritz Scherer, Dr.         
Department of Neurosurgery, University of Schleswig-Holstein, Kiel, Germany Recruiting
Kiel, Germany
Contact: Felix Schwartz, Dr.         
Department of Neurosurgery, Westfälische Wilhelms-Universität Münster, Münster, Germany Recruiting
Münster, Germany
Contact: Walter Stummer, Prof. Dr.         
Department of Neurosurgery, Eberhard Karls University, Tübingen, Recruiting
Tübingen, Germany
Contact: Constantin Roder, Dr.         
Department of Neurosurgery, Julius-Maximilians-Universität Würzburg Recruiting
Würzburg, Germany
Contact: Mario Löhr, PD Dr.         
Sponsors and Collaborators
University Hospital Tuebingen
Investigators
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Principal Investigator: Constantin Roder, Dr. University Hospital Tuebingen, Department of Neurosurgery

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Responsible Party: University Hospital Tuebingen
ClinicalTrials.gov Identifier: NCT02379572     History of Changes
Other Study ID Numbers: Nch1
First Posted: March 5, 2015    Key Record Dates
Last Update Posted: June 13, 2018
Last Verified: May 2018
Keywords provided by University Hospital Tuebingen:
5-ALA
Intraoperative MRI
Extent of resection
Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Aminolevulinic Acid
Photosensitizing Agents
Dermatologic Agents