Glioblastoma MultiformePhase 1POBIGNCT03582514
PreOperative Brain Irradiation in Glioblastoma
A Phase 1 study testing Preoperative brain irradiation (single fraction) in people with Glioblastoma Multiforme, run by The Christie NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
PreOperative Brain Irradiation in Glioblastoma (POBIG) is a phase I study that will test the safety and feasibility of a single fraction of preoperative radiotherapy in patients with a new radiological diagnosis of glioblastoma (GBM). After the single fraction of radiotherapy, patients will receive standard treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme
- What is being tested?
- Preoperative brain irradiation (single fraction)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 19 Apr 2022to 30 Jun 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years.
- Male or female.
- New radiological diagnosis of glioblastoma.
- Performance status judged by World Health Organisation, Eastern Cooperative Oncology Group [ECOG] score = 0-1.
- Case has been reviewed by Neuro-oncology multidisciplinary team (MDT - neurosurgeon, clinical oncologist, radiologist and pathologist); MDT consensus that offering study entry is clinically appropriate and safe i.e. patient unlikely to come to harm (e.g. hydrocephalus) from delayed surgery and pre-operative radiotherapy based on available clinical information and imaging.
- Confirmation at first clinic visit that study entry is clinically appropriate and safe (e.g. lack of severe and debilitating symptoms of raised intracranial pressure).
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- Intention to treat with surgical resection and postoperative adjuvant therapy as per current standard of care (Stupp regimen).
- Tumour size, location and configuration meet radiotherapy treatment planning criteria (e.g. to secure cold spot/hot spot, meets dose constraints for organs at risk when accounting for post-operative radiotherapy).
- Adequate haematological and biochemical parameters for surgery and contrast agent administration (full blood count and coagulation profile deemed acceptable by clinical team, eGFR >30ml/min).
- Mental capacity to consent for treatment.
- Able and willing to give informed consent.
Who cannot join
- Planned biopsy procedure only.
- Suspicion of other tumour on CT body scan or known malignancy except non-melanoma skin cancer, completely resected cervical or prostate cancer (with Prostate Specific Antigen of less than or equal to 0.1 ng/ml) within the past 3 years.
- Contraindications to contrast-enhanced MRI scanning (e.g. claustrophobia, gadolinium allergy).
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
The Christie NHS Foundation Trust
Manchester, Greater Manchester, M20 4BX
Gerben R Borst, MD,PhD
About this study
PreOperative Brain Irradiation in Glioblastoma (POBIG) is a phase I study that will test the safety and feasibility of a single fraction of preoperative radiotherapy in patients with a new radiological diagnosis of glioblastoma (GBM). After the single fraction of radiotherapy, patients will receive standard treatment. The standard treatment consists of resection of the tumor followed by (chemo)radiation (i.e. radiotherapy +/- daily temozolomide (75mg/m2) for 6 weeks (60Gy/30fr) or for 3 weeks (40Gy/15fr)).
Read the detailed description
Glioblastoma is the most common primary malignant brain tumour in adults. Its outcomes are poor due to local disease progression in most patients. Current treatment includes surgery followed by chemotherapy and radiotherapy 4-6 weeks after surgery. In this time interval, some tumour cells do not receive any treatment. Furthermore, studies show that around half of all glioblastoma patients experience rapid early progression (REP) i.e. growth of the tumour in the time interval between surgery and postoperative chemotherapy/radiotherapy. REP is associated with a shorter survival and there are currently no effective treatments or preventative measures to address it. Radiotherapy delivered earlier before the operation could prevent REP and improve patient outcome. In this phase I study - PreOperative Brain Irradiation in Glioblastoma (POBIG), we will test the safety and feasibility of giving a single dose (fraction) of radiotherapy before surgery in patients with a new radiological diagnosis of glioblastoma. This study will be a dose escalation study to determine the maximum tolerated dose of preoperative radiotherapy and maximum volume of tumour that can be safely irradiated preoperatively. We hypothesise that preoperative radiotherapy will reduce the rate of REP and improve patient outcome.
- Conditions
- Glioblastoma Multiforme
- Being tested
- Preoperative brain irradiation (single fraction)
- Keywords
- Radiotherapy, Preoperative, Neoadjuvant
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Preoperative brain irradiation (single fraction)Radiation
Dose and volume escalation of preoperative single-fraction radiotherapy.
| Study group | Role | What they receive |
|---|---|---|
| Dose or volume radiation escalation | Experimental | Patients with a new radiological diagnosis of GBM (judged by the neuro-oncology multidisciplinary team) are to be considered for this study.
This study arm will use 5 radiotherapy doses (6 Gy, 8 Gy, 10 Gy, 12 Gy and 14 Gy) and three treatment volumes (<30 cm3, 30-60 cm3 and >60 cm3). The study will use 6 dosing levels based on a combination of radiotherapy dose and treatment volume. The stepwise inclusion process allows for variation in tumour volume and location. The study will commence with dosing level 1: 8 Gy to <30 cm3 and 6 Gy to 30-60 cm3. In collaboration with the Clinical Trials Unit, the Trial Management Group will enter outcome data for patients at a given dose level into the CRM model. The model output will then guide dose escalation to determine the next dose level. After the single fraction of radiotherapy, patients will receive the standard treatment. Receives: Radiation: Preoperative brain irradiation (single fraction) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) and maximum tolerated irradiation volume (MTIV) of single-fraction preoperative radiotherapy in patients with a new radiological diagnosis of glioblastoma
These will be determined by the following dose limiting complications:
- Radiotherapy related swelling leading to a change of the scheduled date of surgery.
- Post-operative radiotherapy commencement delayed to beyond 6 weeks after surgery due to radiation related symptoms and/or complications from surgery.
- Interruption of post-operative radiotherapy >5 days.
Measured: 18 months
Secondary outcomes (7)
Registration of postoperative surgical complications.
Measured: 18 months
Radiotherapy related complications
Measured: 18 months
Progression free survival.
Measured: 18 months
Overall survival.
Measured: 18 months
Steroid dose after preoperative radiotherapy.
Measured: 18 months
The tumor volume differences measured between the post-surgery MRI and pre-radiotherapy MRI
To confirm usability of the MRI to select GBM patients for preoperative single fraction radiotherapy.
Measured: 18 months
Concordance between MRI based diagnosis of glioblastoma and definitive histological diagnosis.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2018
- Study start19 Apr 2022
- Primary completion30 Jun 2025 (estimated)
- Study completion30 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- The study uses a Continual Reassessment Method (CRM) to inform dose escalation and determine the MTD and MTIV. This is a Bayesian statistics-based model. It uses all available data from previous doses to guide dose escalation.
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Christie NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Liverpool, The Netherlands Cancer Institute, Northern Care Alliance NHS Foundation Trust, University of Manchester
- Responsible party
- Sponsor
- Investigators
- Gerben R Borst, MD, PhD, Principal investigator, The Christie NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03582514
- Sponsor's protocol ID
- CFTSp200
- Other IDs
- 21/NW/0121
- Acronym
- POBIG
- Status last verified
- Nov 2023
- First submitted
- 30 May 2018
- Last updated
- 18 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Waqar M, Roncaroli F, Djoukhadar I, Akkari L, O'Leary C, Hewitt L, Forte G, Jackson R, Hessen E, Withington L, Beasley W, Richardson J, Golby C, Whitehurst P, Colaco R, Bailey M, Karabatsou K, D'Urso PI, McBain C, Coope DJ, Borst GR. Study protocol: PreOperative Brain Irradiation in Glioblastoma (POBIG) - A phase I trial. Clin Transl Radiat Oncol. 2023 Jan 18;39:100585. doi: 10.1016/j.ctro.2023.100585. eCollection 2023 Mar.
PubMed 36845633
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PreOperative Brain Irradiation in Glioblastoma
- ClinicalTrials.gov ID
- NCT03582514
- Acronym / sponsor ID
- POBIG / CFTSp200
- Conditions
- Glioblastoma Multiforme
- Keywords
- Radiotherapy, Preoperative, Neoadjuvant
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- The Christie NHS Foundation TrustUniversity, hospital or other
- Collaborators
- University of Liverpool, The Netherlands Cancer Institute, Northern Care Alliance NHS Foundation Trust, University of Manchester
- Study start
- 19 Apr 2022 (actual)
- Primary completion
- 30 Jun 2025 (estimated)
- Study completion
- 30 Jun 2025 (estimated)
- First posted
- 11 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
PreOperative Brain Irradiation in Glioblastoma (POBIG) is a phase I study that will test the safety and feasibility of a single fraction of preoperative radiotherapy in patients with a new radiological diagnosis of glioblastoma (GBM). After the single fraction of radiotherapy, patients will receive standard treatment. The standard treatment consists of resection of the tumor followed by (chemo)radiation (i.e. radiotherapy +/- daily temozolomide (75mg/m2) for 6 weeks (60Gy/30fr) or for 3 weeks (40Gy/15fr)).
Detailed description
Glioblastoma is the most common primary malignant brain tumour in adults. Its outcomes are poor due to local disease progression in most patients. Current treatment includes surgery followed by chemotherapy and radiotherapy 4-6 weeks after surgery. In this time interval, some tumour cells do not receive any treatment. Furthermore, studies show that around half of all glioblastoma patients experience rapid early progression (REP) i.e. growth of the tumour in the time interval between surgery and postoperative chemotherapy/radiotherapy. REP is associated with a shorter survival and there are currently no effective treatments or preventative measures to address it. Radiotherapy delivered earlier before the operation could prevent REP and improve patient outcome. In this phase I study - PreOperative Brain Irradiation in Glioblastoma (POBIG), we will test the safety and feasibility of giving a single dose (fraction) of radiotherapy before surgery in patients with a new radiological diagnosis of glioblastoma. This study will be a dose escalation study to determine the maximum tolerated dose of preoperative radiotherapy and maximum volume of tumour that can be safely irradiated preoperatively. We hypothesise that preoperative radiotherapy will reduce the rate of REP and improve patient outcome.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The study uses a Continual Reassessment Method (CRM) to inform dose escalation and determine the MTD and MTIV. This is a Bayesian statistics-based model. It uses all available data from previous doses to guide dose escalation.
| Arm | Type | Receives |
|---|---|---|
| Dose or volume radiation escalation | Experimental | Radiation: Preoperative brain irradiation (single fraction)Patients with a new radiological diagnosis of GBM (judged by the neuro-oncology multidisciplinary team) are to be considered for this study. This study arm will use 5 radiotherapy doses (6 Gy, 8 Gy, 10 Gy, 12 Gy and 14 Gy) and three treatment volumes (<30 cm3, 30-60 cm3 and >60 cm3). The study will use 6 dosing levels based on a combination of radiotherapy dose and treatment volume. The stepwise inclusion process allows for variation in tumour volume and location. The study will commence with dosing level 1: 8 Gy to <30 cm3 and 6 Gy to 30-60 cm3. In collaboration with the Clinical Trials Unit, the Trial Management Group will enter outcome data for patients at a given dose level into the CRM model. The model output will then guide dose escalation to determine the next dose level. After the single fraction of radiotherapy, patients will receive the standard treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age ≥18 years.
- Male or female.
- New radiological diagnosis of glioblastoma.
- Performance status judged by World Health Organisation, Eastern Cooperative Oncology Group [ECOG] score = 0-1.
- Case has been reviewed by Neuro-oncology multidisciplinary team (MDT - neurosurgeon, clinical oncologist, radiologist and pathologist); MDT consensus that offering study entry is clinically appropriate and safe i.e. patient unlikely to come to harm (e.g. hydrocephalus) from delayed surgery and pre-operative radiotherapy based on available clinical information and imaging.
Key exclusion criteria (3 listed)
- Planned biopsy procedure only.
- Suspicion of other tumour on CT body scan or known malignancy except non-melanoma skin cancer, completely resected cervical or prostate cancer (with Prostate Specific Antigen of less than or equal to 0.1 ng/ml) within the past 3 years.
- Contraindications to contrast-enhanced MRI scanning (e.g. claustrophobia, gadolinium allergy).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Preoperative brain irradiation (single fraction)Dose and volume escalation of preoperative single-fraction radiotherapy. | Radiation | Dose or volume radiation escalation |
Primary outcome
Maximum tolerated dose (MTD) and maximum tolerated irradiation volume (MTIV) of single-fraction preoperative radiotherapy in patients with a new radiological diagnosis of glioblastoma
Time frame: 18 months
These will be determined by the following dose limiting complications: * Radiotherapy related swelling leading to a change of the scheduled date of surgery. * Post-operative radiotherapy commencement delayed to beyond 6 weeks after surgery due to radiation related symptoms and/or complications from surgery. * Interruption of post-operative radiotherapy >5 days.
7 secondary outcomes
Registration of postoperative surgical complications.
Time frame: 18 months
Radiotherapy related complications
Time frame: 18 months
Progression free survival.
Time frame: 18 months
Overall survival.
Time frame: 18 months
Steroid dose after preoperative radiotherapy.
Time frame: 18 months
The tumor volume differences measured between the post-surgery MRI and pre-radiotherapy MRI
Time frame: 18 months
Concordance between MRI based diagnosis of glioblastoma and definitive histological diagnosis.
Time frame: 18 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2023.
- Derived from this study: PubMed 36845633Waqar M, Roncaroli F, Djoukhadar I, Akkari L, O'Leary C, Hewitt L, Forte G, Jackson R, Hessen E, Withington L, Beasley W, Richardson J, Golby C, Whitehurst P, Colaco R, Bailey M, Karabatsou K, D'Urso PI, McBain C, Coope DJ, Borst GR. Study protocol: PreOperative Brain Irradiation in Glioblastoma (POBIG) - A phase I trial. Clin Transl Radiat Oncol. 2023 Jan 18;39:100585. doi: 10.1016/j.ctro.2023.100585. eCollection 2023 Mar.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gerben R Borst, MD, PhD principal investigator
The Christie NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Preoperative brain irradiation (single fraction) in people with Glioblastoma Multiforme, run by The Christie NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Gerben R Borst, MD, PhD (0161 446 3000, gerben.borst@nhs.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) and maximum tolerated irradiation volume (MTIV) of single-fraction preoperative radiotherapy in patients with a new radiological diagnosis of glioblastoma (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03582514, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2023.