Functional and Ultrasound Guided Resection of Glioblastoma (FUTURE-GB)

May 26, 2022 updated by: University of Oxford

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.

Functional and ultrasound-guided resection of glioblastoma: assessing the use of additional imaging during surgery to improve outcomes for patients with glioblastoma brain tumours

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

357

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United Kingdom
      • Birmingham, United Kingdom, B15 2TH
        • Not yet recruiting
        • Queen Elizabeth Hospital, University Hospitals Birmingham NHSFT
        • Contact:
      • Brighton, United Kingdom, BN2 5BE
      • Bristol, United Kingdom, BS10 5NB
      • Cambridge, United Kingdom, CB2 0QQ
        • Recruiting
        • Addenbrookes Hospital, Cambridge University NHSFT
        • Contact:
      • Cardiff, United Kingdom, CF14 4XW
        • Recruiting
        • University Hospital of Wales, Cardiff & Vale University Health Board
        • Contact:
      • Coventry, United Kingdom, CV2 2DX
      • Dundee, United Kingdom, DD2 1SG
      • Edinburgh, United Kingdom, EH16
        • Recruiting
        • The Royal Infirmary of Edinburgh, NHS Lothian
        • Contact:
      • Hull, United Kingdom, HU3 2JZ
      • Leeds, United Kingdom, LS1 3EX
      • Liverpool, United Kingdom, L9 7LJ
      • London, United Kingdom, SE5 9RS
        • Recruiting
        • King's College Hospital
        • Contact:
      • London, United Kingdom, E1 1BB
      • London, United Kingdom, W6 8RF
      • Middlesbrough, United Kingdom, TS4 3BW
        • Recruiting
        • James Cook University Hospital, South Tees Hospitals NHSFT
        • Contact:
      • Newcastle Upon Tyne, United Kingdom, NE1 4LP
        • Not yet recruiting
        • Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHSFT
        • Contact:
      • Nottingham, United Kingdom, NG7 2UH
      • Oxford, United Kingdom, OX3 9DU
        • Recruiting
        • The John Radcliffe Hospital, Oxford University Hospitals NHSFT
        • Contact:
      • Plymouth, United Kingdom, PL6 8DH
        • Recruiting
        • Derriford Hospital, University Hospitals Plymouth NHS Trust
        • Contact:
      • Preston, United Kingdom, PR2 9HT
        • Not yet recruiting
        • Royal Preston Hospital, Lancashire Teaching Hospitals NHSFT
        • Contact:
      • Romford, United Kingdom, RM7 0AG
        • Not yet recruiting
        • Queen's Hospital, Barking, Havering and Redbridge University Hospitals NHST
        • Contact:
      • Sheffield, United Kingdom, S10 2JF
        • Not yet recruiting
        • Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust
        • Contact:
      • Southampton, United Kingdom
        • Recruiting
        • Southampton General Hospital, University Hospital Southampton NHSFT
        • Contact:
      • Stoke-on-Trent, United Kingdom, ST4 6QG
        • Recruiting
        • Royal Stoke University Hospital, University Hospitals of North Midlands NHST
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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))
Other: Additional pre- and intra-operative imaging
Additional DTI scan during routine pre-operative tumour MRI scan, additional use of intraoperative ultrasound in addition to normal to standard of care (Neuronavigation and intraoperative 5-ALA)
Other Names:
  • DTI
  • IUS
Active Comparator: 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).
Other: Standard of Care
Neuronavigation and intraoperative 5-ALA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: 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.
Measured 6 weeks post-surgery
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)
Time Frame: 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.
Measured from baseline up to 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Stage 2: To assess if additional intraoperative imaging changes DFS where deterioration relates to physical and social functioning, and motor and communication dysfunction
Time Frame: 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.
Measured from baseline up to 24 months
Stage 2: To assess whether additional intraoperative imaging to standard of care changes time to deterioration
Time Frame: 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
Measured from baseline up to 24 months
Stage 2: To assess whether additional intraoperative imaging to standard of care improves Overall Survival (OS)
Time Frame: To be recorded at 24 months
OS (time from randomisation to death or trial closure)
To be recorded at 24 months
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)
Time Frame: 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.
MRI at 6 months post-op., and then 3 monthly up to 24 months or an MRI performed outside protocol if patient is symptomatic
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
Time Frame: Measured 1 week post-surgery
Extent of resection as percent of pre-operative tumour volume on postoperative contrast enhanced MRI
Measured 1 week post-surgery
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
Time Frame: Measured from surgery up to 24 months
Number and type of surgical complications
Measured from surgery up to 24 months
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
Time Frame: Measured 3 months post surgery
Number of patients eligible for adjuvant treatment
Measured 3 months post surgery
Stage 2: To assess whether additional intraoperative imaging (DTI and iUS*) to standard of care (Neuronavigation and intraoperative 5-ALA) changes functional outcome postoperatively
Time Frame: 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.
Measured from baseline up to 24 months
Stage 2: Assess the correlation of proxy to participant classification assessment of quality of life
Time Frame: 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.
Measured from baseline up to 24 months. Proxy will not complete questionnaires when participant stops completing them.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 6 weeks post-surgery

To assess the sensitivity and specificity of the anatomico-spatial location of DTI fibre tracts compared with intraoperative direct electrical stimulation/behavioural change without stimulation but related to adjacent white fibre tract in patients undergoing awake surgery, or motor evoked potential changes in patients undergoing surgery.

Measured by sensitivity and specificity calculation using pre and post-surgery MRI images
6 weeks post-surgery
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.
Time Frame: 6 weeks post-surgery

To assess the sensitivity and specificity of iUS* to identify the tumour boundary when compared with 5-ALA, navigated biopsies will be taken from tumour boundary tissue planned for resection.

Intra operative iUS* images and post-operative MRI scans and Intraoperative biopsy samples
6 weeks post-surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Oxford

Collaborators

Imperial College Healthcare NHS Trust
Efficacy and Mechanism Evaluation (EME) Programme

Investigators

  • Study Director: Puneet Plaha, University of Oxford

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2020

Primary Completion (Anticipated)

October 1, 2025

Study Completion (Anticipated)

November 1, 2025

Study Registration Dates

First Submitted

November 24, 2021

First Submitted That Met QC Criteria

May 26, 2022

First Posted (Actual)

June 1, 2022

Study Record Updates

Last Update Posted (Actual)

June 1, 2022

Last Update Submitted That Met QC Criteria

May 26, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 14763

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Glioma Glioblastoma Multiforme

Clinical Trials on Additional pre- and intra-operative imaging

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Burkina Faso

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe