Clinical trial NCT05399524: Functional and Ultrasound Guided Resection of Glioblastoma
Official title: FUTURE-GB Trial (Functional and Ultrasound-guided Resection of Glioblastoma) A 2-Stage Trial. A Learning Phase Evaluation of Participating Centres, Followed by a Randomised, Controlled Multicentre Phase III Trial.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Glioma Glioblastoma Multiforme
Keywords: DTI
iUS
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: Imperial College Healthcare NHS Trust
name: Efficacy and Mechanism Evaluation (EME) Programme
First posted: 2022-06-01
Enrollment: 357
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: FUTURE-GB is a 2-Stage trial: Stage 1 is a non-randomised multicentre learning and evaluation Stage (IDEAL IIB study), and Stage 2 a prospective, multicentre definitive randomised controlled trial.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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).

Exclusion Criteria:

* Midline/basal ganglia/cerebellum/brainstem GB
* Multifocal GB
* Recurrent GB
* Suspected secondary GB
* Contraindication to MRI

Primary outcomes:
measure: 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.
timeFrame: Measured 6 weeks post-surgery
measure: 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)
timeFrame: Measured from baseline up to 24 months
Secondary outcomes:
measure: Stage 2: To assess if additional intraoperative imaging changes DFS where deterioration relates to physical and social functioning, and motor and communication dysfunction
timeFrame: Measured from baseline up to 24 months
measure: Stage 2: To assess whether additional intraoperative imaging to standard of care changes time to deterioration
timeFrame: Measured from baseline up to 24 months
measure: Stage 2: To assess whether additional intraoperative imaging to standard of care improves Overall Survival (OS)
timeFrame: To be recorded at 24 months
measure: 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)
timeFrame: MRI at 6 months post-op., and then 3 monthly up to 24 months or an MRI performed outside protocol if patient is symptomatic
measure: 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
timeFrame: Measured 1 week post-surgery
measure: 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
timeFrame: Measured from surgery up to 24 months
measure: 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
timeFrame: Measured 3 months post surgery
measure: Stage 2: To assess whether additional intraoperative imaging (DTI and iUS*) to standard of care (Neuronavigation and intraoperative 5-ALA) changes functional outcome postoperatively
timeFrame: Measured from baseline up to 24 months
measure: Stage 2: Assess the correlation of proxy to participant classification assessment of quality of life
timeFrame: Measured from baseline up to 24 months. Proxy will not complete questionnaires when participant stops completing them.
Other outcomes:
measure: Tertiary Mechanistic Objectives (on a sub set of participants): assessment of the sensitivity and specificity of the anatomico-spatial location of DTI fibre tracts compared to Standard of Care
timeFrame: 6 weeks post-surgery
measure: Tertiary Mechanistic Objectives (on a sub set of participants): assessment of the sensitivity and specificity of iUS to identify the tumour boundary when compared with 5-ALA.
timeFrame: 6 weeks post-surgery
Locations:
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital, University Hospitals Birmingham NHSFT
city: Brighton
country: United Kingdom
facility: Royal Sussex County Hospital
city: Bristol
country: United Kingdom
facility: Southmead Hospital, North Bristol NHST
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital, Cambridge University NHSFT
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales, Cardiff & Vale University Health Board
city: Coventry
country: United Kingdom
facility: University Hospital, Coventry
city: Dundee
country: United Kingdom
facility: Ninewells Hospital, NHS Tayside
city: Edinburgh
country: United Kingdom
facility: The Royal Infirmary of Edinburgh, NHS Lothian
city: Hull
country: United Kingdom
facility: Hull Royal Infirmary
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: Liverpool
country: United Kingdom
facility: The Walton Centre
city: London
country: United Kingdom
facility: Royal London Hospital, Barts Health NHS Trust
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: Charing Cross Hospital/St Mary's, Imperial College Healthcare NHS Trust
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital, South Tees Hospitals NHSFT
city: Newcastle Upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHSFT
city: Nottingham
country: United Kingdom
facility: Queen's Medical Centre, Nottingham University Hospitals NHST
city: Oxford
country: United Kingdom
facility: The John Radcliffe Hospital, Oxford University Hospitals NHSFT
city: Plymouth
country: United Kingdom
facility: Derriford Hospital, University Hospitals Plymouth NHS Trust
city: Preston
country: United Kingdom
facility: Royal Preston Hospital, Lancashire Teaching Hospitals NHSFT
city: Romford
country: United Kingdom
facility: Queen's Hospital, Barking, Havering and Redbridge University Hospitals NHST
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust
city: Southampton
country: United Kingdom
facility: Southampton General Hospital, University Hospital Southampton NHSFT
city: Stoke-on-Trent
country: United Kingdom
facility: Royal Stoke University Hospital, University Hospitals of North Midlands NHST
Study officials:
affiliation: University of Oxford
name: Puneet Plaha
role: STUDY_DIRECTOR
References: