Repeat surgery for recurrent glioblastoma
| ISRCTN | ISRCTN12749687 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN12749687 |
| Integrated Research Application System (IRAS) | 358925 |
| Central Portfolio Management System (CPMS) | 62049 |
| Sponsor | University of Oxford |
| Funders | National Institute for Health and Care Research, BrainStorm Charity |
- Submission date
- 05/02/2026
- Registration date
- 25/02/2026
- Last edited
- 25/02/2026
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
Glioblastoma (GB) is the most common type of brain cancer in adults, with around 3,200 new cases in the UK each year. Without treatment, average survival is less than 6 months. With surgery to remove as much cancer as possible, followed by radiotherapy and chemotherapy (temozolomide), survival can extend to 14-16 months. Despite this, the tumour inevitably grows back and is called a ‘recurrent GB’. It is unclear what the most appropriate treatment for recurrent GB is. As a result, there is a wide variation in practice across the UK in whether or not patients are offered repeat surgery or whether to use only non-surgical treatments (chemotherapy and/or radiotherapy).
This study will determine if repeat surgery when a GB grows back, before further chemotherapy or radiotherapy, improves quality of life and survival. It was co-designed with UK-wide patient and relative advisory groups from the BrainsTrust charity, Brain Tumour Charity Research Involvement Network (BTC-RIN), Thames Valley Patient & Public Involvement (PPI) group, and specialist nurses who care for patients with GB.
Who can participate?
Adults will be recruited from at least 20 UK NHS hospitals who are aged 18 years and above, have previously undergone surgery to remove a GB, are now diagnosed with a recurrent GB, and have not experienced recurrence or progression within 6 weeks of completing radiotherapy (6-week or short course), with or without concomitant chemotherapy.
What does the study involve?
As part of routine NHS care, patients with recurrent GB will be discussed in a ‘multi-disciplinary team’ (MDT) meeting, where a group of medical specialists will discuss treatment options. If the MDT considers both repeat surgery and second-line chemotherapy reasonable, the patient will be invited to participate in this trial. If they agree to take part, they will be assigned at random to one of two groups:
Group 1: Offered repeat surgery followed by further chemotherapy and/or radiotherapy
Group 2: Offered further chemotherapy and/or radiotherapy without repeat surgery
Participants will be followed up weekly with three questions rating their general health and quality of life, plus additional questionnaires on various aspects of their health and quality of life every 6 weeks. Depending on participant preference, responses will be collected electronically via a smartphone app (RADAR-base) or via links to an online form sent by email/text, or via a telephone interview. If participants choose to complete questionnaires using the RADAR-based app, they will also be invited to provide optional short speech samples, which may offer insights into aspects of well-being.
The study also requires participants to nominate a ‘proxy’, ideally who will be their primary carer*/support through their treatment (family member/friend), to complete similar questionnaires about the participant’s quality of life, as they may not always feel well enough to respond and at three timepoints, their own quality of life. Nominated proxies will be provided with a Proxy Information Sheet and invited to give their consent to complete questionnaires on behalf of the participant. The follow-up period of the trial is up to 12 months post-randomisation. Due to the natural history of recurrent glioblastoma, some participants may pass away prior to this time point.
In addition to the health and quality of life questionnaires described above, participants will be invited to take part in an optional component of the trial, which aims to measure their physical activity levels using a smartwatch. Participants who wish to participate in this part of the trial will be provided with a complimentary smartwatch and asked to wear it for a minimum of 7 days every six weeks, to coincide with when they fill out their 6-weekly questionnaires. Physical activity data (e.g. activity levels, sleep patterns and, where supported by the device, time spent at home) will be collected remotely by researchers.
No additional blood tests or hospital visits are required from participants.
The trial will also look at the costs involved in treatment of recurrent glioblastoma to determine which treatment combination offers the best value for money to the NHS.
What are the possible benefits and risks of participating?
Benefits and risks not provided at time of registration
Where is the study run from?
John Radcliffe Hospital, Headington, UK.
When is the study starting and how long is it expected to run for?
April 2026 to March 2030.
Who is funding the study?
1. National Institute for Health and Care Research, UK.
2. BrainStorm Charity (Smartwatches for Substudy), UK.
Who is the main contact?
Recurrent GB team, recurrentgb@nds.ox.ac.uk
Contact information
Principal investigator, Scientific
John Radcliffe Hospital, Headington
Oxford
OX3 9DU
United Kingdom
| Phone | +441865 234838 |
|---|---|
| Puneet.Plaha@ouh.nhs.uk |
Public
Surgical Intervention Trials Unit (SITU)
University of Oxford
Botnar Research Centre
Nuffield Orthopaedic Centre
Old Road
Headington
Oxford
OX3 7LD
United Kingdom
| Phone | +447917101649 |
|---|---|
| recurrentgb@nds.ox.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Allocation | Randomized controlled trial |
| Masking | Open (masking not used) |
| Control | Active |
| Assignment | Parallel |
| Purpose | Treatment |
| Scientific title | RECURRENT-GB: Repeat ExCision Upon Recurrence: REthinking Neurosurgical Treatment of GlioBlastoma |
| Study acronym | RECURRENT-GB |
| Study objectives | Primary Objective: In participants with a recurrent GB, does repeat tumour resection surgery improve quality of life and survival when added to second-line medical therapy? |
| Ethics approval(s) |
Not yet submitted |
| Health condition(s) or problem(s) studied | Repeat surgery for patients with recurrent glioblastoma |
| Intervention | This is a two-arm, pragmatic randomised controlled trial in adults with recurrent glioblastoma (GB). Participants will be followed for a maximum of 12 months from randomisation. Intervention arm: Repeat maximal safe resection followed by second-line medical therapy Participants randomised to the intervention arm will undergo repeat surgical resection of recurrent GB in the hospital. The aim of surgery is maximal safe resection and it is expected that the operating surgeon will use pre-operative MRI with diffusion tensor imaging (DTI) tractography for neuronavigation, as well as 5-aminolevulinic acid (5-ALA) intra-operative fluorescence. The operating surgeon may additionally use other adjuncts at their discretion to maximise safe resection, including intra-operative neuromonitoring, awake craniotomy with neuropsychological assessment, intra-operative ultrasound, or intra-operative MRI. Post-operative care will follow routine NHS practice, including a brain MRI with gadolinium contrast within 48–72 hours to assess the extent of resection. Following recovery from surgery, participants will receive all appropriate second-line medical therapies as determined by their multidisciplinary team (MDT), in accordance with national guidance and local NHS policy. There are no protocol-imposed restrictions on systemic therapy. Comparator arm: Standard of care (SOC) alone Participants randomised to the control arm will receive second-line treatment as recommended by their neuro-oncology MDT and in line with national guidance and local NHS practice. As there is no single standard treatment for recurrent GB, management may include chemotherapy, radiotherapy, re-irradiation, and repeat surgery if clinically indicated. No trial-mandated surgical intervention is delivered in this arm. All other aspects of clinical care will be as per routine NHS practice. Follow-up and assessments All participants will receive standard NHS follow-up. Participants will be asked to complete patient-reported outcome questionnaires during follow-up, which may be completed remotely via an online link (sent via email or SMS), via a trial-specific app, or by phone with the research team. Participants will be followed for up to 12 months from randomisation. Randomisation Participants will be randomised in a 1:1 ratio to either repeat maximal safe resection followed by second-line medical therapy or second-line medical therapy alone. Randomisation will take place after confirmation of eligibility, informed consent, and completion of baseline assessments. Allocation will be performed by authorised site research staff using a secure, web-based REDCap system hosted by the Oxford Clinical Trials Research Unit (OCTRU). Minimisation with a random component will be used to ensure balance across treatment arms. A small number of initial participants will be allocated using simple randomisation to seed the minimisation algorithm. Minimisation factors are: Baseline QLQ-C30 Global Health Status score (<10 vs ≥10), Age (<70 vs ≥70 years), Tumour location (eloquent vs non-eloquent), Timing of recurrence (before vs after 6th cycle of adjuvant temozolomide), Previous radiotherapy (≤3-week vs standard 6-week course), MGMT methylation status (unknown grouped with unmethylated), Recruiting centre. |
| Intervention type | Procedure/Surgery |
| Primary outcome measure(s) |
|
| Key secondary outcome measure(s) |
|
| Completion date | 31/03/2030 |
Eligibility
| Participant type(s) | |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Upper age limit | 120 Years |
| Sex | All |
| Target sample size at registration | 150 |
| Key inclusion criteria | 1. Aged 18 years or above 2. First recurrence/progression of IDH wild-type GB following previous maximal safe resection (attempted gross total resection of contrast-enhancing tumour) as confirmed by local Neuro-oncology Multidisciplinary Team (MDT) 3. WHO Performance Status 0-2 4. Neuro-oncology MDT feels that the patient should be offered the trial and confirms that repeat maximal safe resection (>90%) is feasible and a reasonable treatment option 5. Able to give informed consent 6. Able to provide a proxy who is willing to complete the trial questionnaires |
| Key exclusion criteria | 1. Recurrence/progression of GB within 6 weeks of completion of radiotherapy (6 weeks or short course), with or without concomitant chemotherapy (See note* below) 2. Multifocal recurrence/progression of GB 3. Contraindication to MRI 4. Glioblastoma located in the brainstem, basal ganglia or the thalamus *In the UK, standard treatment for operable glioblastoma consists of surgery followed by radiotherapy (with or without concomitant chemotherapy), then a short treatment break before starting adjuvant chemotherapy. The exclusion criterion refers to recurrence or progression occurring within 6 weeks of completing radiotherapy. Patients are therefore only eligible for RECURRENT GB once they have completed radiotherapy and reached the point at which adjuvant chemotherapy would normally begin, or are further along in their treatment pathway. |
| Date of first enrolment | 01/04/2026 |
| Date of final enrolment | 31/03/2029 |
Locations
Countries of recruitment
- United Kingdom
- England
- Scotland
- Wales
Study participating centres
80 Newark Street
London
E1 2ES
England
A Floor - Belfast City Hospital
Lisburn Road
Belfast
BT9 7AB
England
Mindelsohn Way
Edgbaston
Birmingham
B15 2GW
England
Southmead Road
Westbury-on-trym
Bristol
BS10 5NB
England
Hills Road
Cambridge
CB2 0QQ
England
Maes-y-coed Road
Cardiff
CF14 4HH
Wales
Clifford Bridge Road
Coventry
CV2 2DX
England
2-4 Waterloo Place
Edinburgh
EH1 3EG
Scotland
Anlaby Road
Hull
HU3 2JZ
England
St Marys Hospital
South Wharf Road
London
W2 1BL
England
London
SE5 9RS
England
Beckett Street
Leeds
LS9 7TF
England
Fazakerley
Liverpool
L9 7LJ
England
Stott Lane
Salford
M6 8HD
England
Marton Road
Middlesbrough
TS4 3BW
England
Derby Road
Nottingham
NG7 2UH
England
Derriford Road
Derriford
Plymouth
PL6 8DH
England
Sharoe Green Lane
Fulwood
Preston
PR2 9HT
England
Rom Valley Way
Romford
RM7 0AG
England
Tremona Road
Southampton
SO16 6YD
England
Stoke-on-trent
ST4 6QG
England
London
NW1 2PG
England
Headley Way
Headington
Oxford
OX3 9DU
England
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|
Editorial Notes
12/02/2026: Study's existence confirmed by the National Institute for Health and Care Research (NIHR) (UK).
