Functional and Ultrasound Guided Resection of Glioblastoma
- Conditions
- Glioma Glioblastoma Multiforme
- Interventions
- Other: Additional pre- and intra-operative imagingOther: Standard of Care
- Registration Number
- NCT05399524
- Lead Sponsor
- University of Oxford
- Brief Summary
Functional and ultrasound-guided resection of glioblastoma: assessing the use of additional imaging during surgery to improve outcomes for patients with glioblastoma brain tumours
- Detailed Description
Stage 1 (IDEAL IIB study) of the trial is observational only and all participants will receive all technologies during surgery.
Stage 2 will be randomised. Randomisation will be via the web-based service provided by the Oxford Clinical Trials Research Unit (OCTRU), using the method of minimisation. Participants will be randomised 1:1 to either:
1. Standard care surgery (neuronavigation based on preoperative imaging and intraoperative use of 5-ALA)(Control arm)
2. Standard care surgery (neuronavigation based on preoperative imaging and intraoperative use of 5-ALA) AND of DTI neuronavigation and NiUS (Intervention arm)
At baseline all participants will undergo a routine preoperative neuronavigation MRI scan. Those participants randomised to the experimental arm, will also have a DTI scan (additional 5 minutes in the MRI). All participants will then undergo the planned resection of their tumour, with the additional technologies if they are in the experimental arm. Following surgery, participants in both arms have the same follow up schedule and undergo standard clinical care for a total of 24 months.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 357
- Age 18-70 years
- Neuro-oncology Multi-Disciplinary Team (MDT) decision that the imaging shows a primary GB tumour which is maximally resectable (attempted gross total resection of all enhancing tumour)
- Patient is suitable for concomitant adjuvant radiotherapy and Temozolomide (TMZ) chemotherapy or adjuvant TMZ at the time of MDT decision
- Able to receive 5-ALA
- Willing and able to give informed consent
- Able to complete trial questionnaires, this may be with support where English is not their first language. (Stage 2 only)
- Able to provide a proxy who is willing to complete questionnaires as requested (Stage 2 only).
- Midline/basal ganglia/cerebellum/brainstem GB
- Multifocal GB
- Recurrent GB
- Suspected secondary GB
- Contraindication to MRI
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Additional pre- and intra-operative imaging Additional pre- and intra-operative imaging Surgery to resect the GB using Diffusion Tensor Imaging (DTI) and intraoperative Ultrasound (iUS) (navigated iUS where available) in addition to standard care (i.e. neuronavigation based on preoperative MRI and intraoperative use of 5-aminolevulinic acid (5-ALA)) Standard of Care Standard of Care The comparator is standard care as per current NICE guidelines (i.e. neuronavigation based on preoperative MRI and intraoperative use of 5-ALA).
- Primary Outcome Measures
Name Time Method Stage 2 Primary Outcome: to assess whether additional imaging to standard of care changes Deterioration Free Survival (DFS) (Where deterioration relates to global health status only) Measured from baseline up to 24 months This is measured by a composite of:
1. Change in global health status domain of the QLQ-C30 questionnaire (Quality of Life Questionnaire Cancer) from baseline to final questionnaire completion. Questionnaires are administered at baseline, 6 weeks, then every 3 months until 24months.
2. Progression Free Survival (PFS). This is measured by radiological tumour progression on imaging, which is taken 3-months post-op and 3-monthly thereafter.
3. Overall Survival (OS) with an event defined as either deterioration, progression or death.Stage 1 Primary Outcome: to demonstrate the feasibility of using DTI and iUS in addition to standard of care for neurosurgery using a combination of qualitative and quantitative data to prove workflow capability at each site. Measured 6 weeks post-surgery Sites are qualitatively assessed through a standardisation stage, providing feedback to enable learning and ensure the workflow is followed. Sites with satisfactory data will "progress" and pass into Stage 2.
The measures assessed in combination are:
1. Operation length, in normal range for this surgery.
2. Use of DTI neuronavigation \& iUS to achieve maximal safe tumour resection without major neurological deficit, measured by getting clear, relevant images for the DTI \& US scans, and accurate pre-operative tractography.
3. Extent of tumour resection (cm³ remaining) on postoperative MRI scan.
4. Surgical Complications/Serious Adverse Events-measured from recorded post-operative complications and a 6-month notes check to ensure patient safety.
If the assessment panel is satisfied with the data after \~3 recruits, a site will progress into Stage 2 of the trial, the RCT. Data will be analysed for Stage 1 once all sites have progressed through into Stage 2 of the trial.
- Secondary Outcome Measures
Name Time Method Stage 2: To assess whether additional intraoperative imaging (DTI and iUS*) to standard of care (Neuronavigation and intraoperative 5-ALA) changes Progression Free Survival (PFS) MRI at 6 months post-op., and then 3 monthly up to 24 months or an MRI performed outside protocol if patient is symptomatic PFS (time from randomisation to radiological tumour progression on imaging, as agreed in local MDT
This involves using the post-operative MRI scan as a reference point and making comparisons will the ensuing MRI reports that are recieved 3 months post-surgery and 3 monthly thereafter until 24 months post-surgery.Stage 2: Assess the correlation of proxy to participant classification assessment of quality of life Measured from baseline up to 24 months. Proxy will not complete questionnaires when participant stops completing them. Assessed using comparisons between the patient and proxy responses to the Quality of Life questionnaires administered. Specifically comparisons between the answers to questions 29 and 30 of the QLQ-C30.
Stage 2: To assess whether additional intraoperative imaging (DTI and iUS*) to standard of care (Neuronavigation and intraoperative 5-ALA) changes the incidence of surgical complications Measured from surgery up to 24 months Number and type of surgical complications
Stage 2: To assess whether additional intraoperative imaging to standard of care changes time to deterioration Measured from baseline up to 24 months Defined similar to DFS with the exception that progression is excluded as an event (i.e. only deterioration or death are considered). There will be five time to deterioration outcomes, one for each of the domains utilised in the primary and secondary DFS outcomes, used in turn to define deterioration
Stage 2: To assess whether additional intraoperative imaging to standard of care improves Overall Survival (OS) To be recorded at 24 months OS (time from randomisation to death or trial closure)
Stage 2: To assess whether additional intraoperative imaging (DTI and iUS*) to standard of care (Neuronavigation and intraoperative 5-ALA) changes the number of patients eligible for adjuvant treatment following surgery Measured 3 months post surgery Number of patients eligible for adjuvant treatment
Stage 2: To assess whether additional intraoperative imaging (DTI and iUS*) to standard of care (Neuronavigation and intraoperative 5-ALA) changes functional outcome postoperatively Measured from baseline up to 24 months Measured by any change in the functional performance assessment which consistes of a combination of:
1. The WHO (World Health Organisation) performance status
2. A 5-minute telephone mini-MoCA (The Montreal Cognitive Assessment, Montreal Version)
3. Barthel Index
4. MRC (Medical Research Council) grading of power in all 4 limbs
Assessments are made at baseline, at hospital discharge, 6 weeks post-op, 3 months post-op, then 3 monthly thereafter until 24 months.Stage 2: To assess if additional intraoperative imaging changes DFS where deterioration relates to physical and social functioning, and motor and communication dysfunction Measured from baseline up to 24 months This is measured using a combination of specific questions (physical functioning and social functioning) in the QLQ-C30 (Quality of Life Questionnaire Cancer) and BN20 questionnaire (Quality of Life Questionnaire Brain) (motor dysfunction and communication deficit questions), combined with the values of Progression Free Survival (PFS) and overall survival (OS) taken from the primary outcome.
Questionnaires are administered at baseline, 6 weeks, then every 3 months until 24months.Stage 2: To assess whether additional intraoperative imaging (DTI and iUS*) to standard of care (Neuronavigation and intraoperative 5-ALA) changes the extent of tumour resection Measured 1 week post-surgery Extent of resection as percent of pre-operative tumour volume on postoperative contrast enhanced MRI
Trial Locations
- Locations (24)
Addenbrookes Hospital, Cambridge University NHSFT
🇬🇧Cambridge, United Kingdom
University Hospital, Coventry
🇬🇧Coventry, United Kingdom
Queen's Medical Centre, Nottingham University Hospitals NHST
🇬🇧Nottingham, United Kingdom
Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust
🇬🇧Sheffield, United Kingdom
Southampton General Hospital, University Hospital Southampton NHSFT
🇬🇧Southampton, United Kingdom
Royal Stoke University Hospital, University Hospitals of North Midlands NHST
🇬🇧Stoke-on-Trent, United Kingdom
Queen Elizabeth Hospital, University Hospitals Birmingham NHSFT
🇬🇧Birmingham, United Kingdom
Southmead Hospital, North Bristol NHST
🇬🇧Bristol, United Kingdom
Royal Sussex County Hospital
🇬🇧Brighton, United Kingdom
University Hospital of Wales, Cardiff & Vale University Health Board
🇬🇧Cardiff, United Kingdom
Hull Royal Infirmary
🇬🇧Hull, United Kingdom
King's College Hospital
🇬🇧London, United Kingdom
Royal London Hospital, Barts Health NHS Trust
🇬🇧London, United Kingdom
Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHSFT
🇬🇧Newcastle Upon Tyne, United Kingdom
The John Radcliffe Hospital, Oxford University Hospitals NHSFT
🇬🇧Oxford, United Kingdom
Royal Preston Hospital, Lancashire Teaching Hospitals NHSFT
🇬🇧Preston, United Kingdom
Queen's Hospital, Barking, Havering and Redbridge University Hospitals NHST
🇬🇧Romford, United Kingdom
The Royal Infirmary of Edinburgh, NHS Lothian
🇬🇧Edinburgh, United Kingdom
Ninewells Hospital, NHS Tayside
🇬🇧Dundee, United Kingdom
Leeds General Infirmary
🇬🇧Leeds, United Kingdom
The Walton Centre
🇬🇧Liverpool, United Kingdom
James Cook University Hospital, South Tees Hospitals NHSFT
🇬🇧Middlesbrough, United Kingdom
Charing Cross Hospital/St Mary's, Imperial College Healthcare NHS Trust
🇬🇧London, United Kingdom
Derriford Hospital, University Hospitals Plymouth NHS Trust
🇬🇧Plymouth, United Kingdom