Condition category
Cancer
Date applied
07/05/2020
Date assigned
14/08/2020
Last edited
14/08/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

Background and study aims
Glioblastoma (GB) is the most common primary brain tumour and is incurable. It grows very quickly from the brain tissue itself, rather than from a cancer elsewhere in the body. It is expected that the number of people with a brain tumour will rise by 6% in the UK between 2014 and 20351. However, prognosis (outcome) remains extremely poor, with most people surviving just over 12 months, and as a patients tumour grows patients experience a reduction (decline) in their quality of life. Therefore, we need to ensure quality of life, which remains difficult. The main treatments for GB are surgery, radiotherapy and chemotherapy, given in combination.
For patients where it is thought that surgery will benefit, a surgeon often removes as much tumour as possible, whilst limiting the risk of causing damage, such as weakness, speech, or cognitive difficulties. However, which technology a surgeon should use during surgery to remove the tumour safely is unclear. This can affect how soon the cancer returns, what effects of surgery or symptoms a patient develops, and how a patient feels.
High frequency sound waves that create an image, called Ultrasound (US), is one of the tools a surgeon can use during the operation to find the tumour and see how much is removed. Another technology, Diffusion Tensor Imaging (DTI), allows important nerve pathways involved in certain functions, for example, speech/language, vision and movement, to be avoided in surgery.
This trial aims to see if GB surgery with these extra technologies (tools) added to the standard ones, increases a patient’s good functioning quality of life, so-called Deterioration Free Survival (DFS).

Who can participate?
Adults aged 18 - 75 years, with a primary GB tumour which is maximally resectable and are suitable candidates for the treatment under investigation.

What does the study involve?
Participants will be randomly allocated to receive either brain surgery with standard methods without US and DTI, or surgery with the addition of US and DTI as well as standard tools. Patients may not know into which group they have been placed. They will be recruited from at least 15 NHS hospitals that routinely undertake GB surgery and have access to these tools. The trial will result in only minor changes to the present care pathway. After agreeing to take part, participants will be asked to complete questionnaires about their quality of life, such as their walking, ability to look after their personal hygiene, how they feel. They will also have a brief physical and cognitive/functional assessment before their surgery. Afterwards, the questionnaires and assessments will be repeated, before leaving hospital, and at three monthly intervals until 24 months after agreeing to take part (consenting). These will be combined with planned hospital visits. How long a patient lives will also be recorded.

What are the possible benefits and risks of participating?
There may not be any direct benefit to the patient, however, information gathered will benefit future patients.
There are no additional risks.

Where is the study run from?
John Radcliffe Hospital (UK)

When is the study starting and how long is it expected to run for?
April 2020 to September 2023

Who is funding the study?
National Institute for Health Research EME Programme (UK)

Who is the main contact?
Mr Damian Haywood, futuregb@nds.ox.ac.uk

Lay summary under review with external organisation

Trial website

Contact information

Type

Public

Primary contact

Ms Amy Jones

ORCID ID

http://orcid.org/0000-0002-8635-7953

Contact details

SITU
Botnar Research Centre
Windmill Road
Oxford
OX3 7LD
United Kingdom
+44 (0)1865 223464
futuregb@nds.ox.ac.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

IRAS 264482, CPMS 45956

Study information

Scientific title

Functional and Ultrasound guided Resection of Glioblastoma. A two stage trial. Stage 1 – Non-randomised collaborative learning and evaluation phase of participating centres (IDEAL Stage 2b study), followed by Stage 2 – A Multicentre Phase III trial with 2 mechanistic substudies.

Acronym

FUTURE-GB

Study hypothesis

This trial aims to see if GB surgery with ultrasound and diffusion tensor imaging added to the standard care, increases a patient’s good functioning quality of life, so-called Deterioration Free Survival (DFS).

Ethics approval

Not provided at time of registration

Study design

Multicentre randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Quality of life

Patient information sheet

Not available in web format. please use contact details to request a participant information sheet.

Condition

Glioblastoma

Intervention

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.

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measure

Stage 1:
Feasibility of using DTI and NiUS in addition to standard of care for neurosurgery assessed using:
1. Operation length measured using patient records, analysed post-operatively
2. Successful use of the technology measured using operating surgeon theatre reports completed during surgery and analysed post-operatively
3. Tumour resection shown by pre and post-op MRI scan
4. Surgical complications measured using number of return visits to theatre, and other medical complications and analysed at discharge

Stage 2:
Deterioration Free Survival (Global Health Status) measured using a composite measure obtained from the QLQ-C30 patient and proxy questionnaire at baseline, 5 days post-op/discharge, 6 weeks post-op, 3 month post-op, then every 3 months subsequently up to 24 months post-op, Progression-Free Survival (PFS) and Overall Survival (OS) measured using patient records

Secondary outcome measures

Measured at baseline, 5 days post-op/discharge, 6 weeks post-op, 3 month post-op, then every 3 months subsequently up to 24 months post-op (unless otherwise mentioned):
1. Physical functioning, social functioning measured using the QLQ-C30
2. Motor dysfunction and communication deficit measured using the QLQ-BN20
3. Time to deterioration measured using a composite measure obtained from the QLQ-C30 patient and proxy questionnaire, Progression-Free Survival (PFS) and Overall Survival (OS) measured using patient records
4. Progression Free Survival (PFS) measured as time from randomisation to radiological tumour progression on imaging
5. Extent of tumour resection measured as % of pre-operative tumour volume on postoperative contrast enhanced MRI at post-op review
6. Incidence of Surgical Complications measured using patient records
7. Number of patients eligible for adjuvant treatment (for radiotherapy and/or chemotherapy) following surgery measured using patient records
8. Functional Outcome measured by results from standardised assessments:
8.1. Activity ability measured using WHO performance status
8.2. Cognitive function measured using Montreal Cognitive Assessment (MOCA)
8.3. Performance in activities of daily living measured using the Barthel Index
8.4. Muscle power measured using MRC grading of power in all 4 limbs
9. Participant classification assessment of quality of life, measured by answers to QoL questions provided by the participant and their proxy

Stage 2 tertiary outcome measures:
1. Location of nerve tracts measured using DTI imaging pre and post-surgery
2. Location of nerve tracts measured using intraoperative direct electrical stimulation or motor evoked potential changes during surgery
3. Location of tumour boundary measured using intraoperative NiUS images
4. Location of tumour boundary measured using post-operative MRI scans
5. Location of tumour boundary measured using intraoperative biopsy samples

Overall trial start date

01/04/2020

Overall trial end date

01/09/2023

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Age 18 - 75 years
2. 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)
3. Patient is suitable for concomitant 6 weeks adjuvant radiotherapy and Temozolamide (TMZ) chemotherapy or adjuvant TMZ at the time of MDT decision
4. Willing and able to give informed consent
5. Able to understand written English to enable completion of trial questionnaires
6. Able to provide a proxy who is willing to complete questionnaires as requested

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

357

Participant exclusion criteria

1. Midline/basal ganglia/cerebellum/brainstem GB
2. Multifocal GB
3. Recurrent GB
4. Suspected secondary GB
5. Contraindication to MRI

Recruitment start date

01/01/2021

Recruitment end date

01/01/2022

Locations

Countries of recruitment

United Kingdom

Trial participating centre

John Radcliffe Hospital
Oxford University Hospitals NHS Trust Headley Way Headington
Oxford
OX3 9DU
United Kingdom

Sponsor information

Organisation

University of Oxford

Sponsor details

Research Services
University Offices
Wellington Square
Oxford
OX1 2JD
United Kingdom
+44 1865 289885
ctrg@admin.ox.ac.uk

Sponsor type

University/education

Website

https://researchsupport.admin.ox.ac.uk/ctrg

Funders

Funder type

Government

Funder name

National Institute for Health Research EME Programme

Alternative name(s)

NIHR

Funding Body Type

unknown

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal.

IPD sharing statement:
The current data sharing plans for this study are unknown and will be available at a later date.

Intention to publish date

01/01/2024

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

28/07/2020: Trial’s existence confirmed by National Institute for Health Research (NIHR).