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

• ClinicalTrials.gov Identifier: NCT02379572
• Recruitment Status: Completed
• First Posted: March 5, 2015
• Last Update Posted: October 22, 2021
• Sponsor: University Hospital Tuebingen
• Information provided by (Responsible Party): University Hospital Tuebingen

Tracking Information

• First Submitted Date: February 18, 2015
• First Posted Date: March 5, 2015
• Last Update Posted Date: October 22, 2021
• Study Start Date: June 2015
• Actual Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 26, 2015)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 26, 2015)

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

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: February 26, 2015)

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)

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: 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

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 Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Condition: 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.

Study Arms

• Experimental: iMRI-guided surgery
  Resection of Glioblastomas with iMRI-guidance
  Intervention: Device: iMRI-guided surgery
• Active Comparator: 5-ALA-guided surgery
  Resection of Glioblastomas with 5-ALA-fluorescence-guidance
  Intervention: Drug: 5-ALA-guided surgery

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 10, 2020): 315
• Original Estimated Enrollment (submitted: February 26, 2015): 276
• Actual Study Completion Date: July 1, 2021
• Actual Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT02379572
• Other Study ID Numbers: Nch1
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: University Hospital Tuebingen
• Original Responsible Party: Same as current
• Current Study Sponsor: University Hospital Tuebingen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Constantin Roder, Dr.; University Hospital Tuebingen, Department of Neurosurgery

• PRS Account: University Hospital Tuebingen
• Verification Date: July 2020