OligodendrogliomaPRO-GLIONCT05190172
PRO-GLIO: PROton Versus Photon Therapy in IDH-mutated Diffuse Grade II and III GLIOmas
A study testing Radiation therapy in people with Oligodendroglioma and Oligodendroglioma, Anaplastic, run by Oslo University Hospital at 1 site in Norway.
Trial summary
Proton therapy is a powerful tool enabling oncologists to spare normal tissue around the target for irradiation much better than what can be achieved with photon irradiation. The infiltrative nature of IDH-mutated grade II and III diffuse glioma, however, renders proton therapy a potential problem. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Oligodendroglioma, Oligodendroglioma, Anaplastic, Diffuse Astrocytoma, IDH-Mutant
- What is being tested?
- Radiation therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 225 participants
- Where
- 1 siteNorway
- Study dates
- 14 Jan 2022to 31 Dec 2045
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Prior treatment (except surgery) for diffuse glioma
- Concomitant or previous malignancies. Exceptions are adequately treated basal cell carcinoma or squamous cell carcinoma of the skin, or in situ carcinoma of the cervix uteri with a follow-up time of at least 3 years, or other previous malignancy with a disease-free interval of at least 5 years
- Known CDKN2A/B homozygous deletion
- Presence of any medical, psychological, familial, sociological, or geographical characteristic that might impair patient compliance for study protocol procedures including follow-up
- Body weight > 150 kg
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Norway1 site, 1 recruiting
- Recruiting
Oslo University Hospital
Oslo
Petter Brandal, MD Phd, +47 22935843, pebra@ous-hf.no
About this study
Proton therapy is a powerful tool enabling oncologists to spare normal tissue around the target for irradiation much better than what can be achieved with photon irradiation. The infiltrative nature of IDH-mutated grade II and III diffuse glioma, however, renders proton therapy a potential problem. A randomized controlled trial (RCT) is the only option when trying to ensure that chances of long-term survival are not impaired seeking to reduce unwanted late treatment effects. Non-inferiority of proton therapy compared to photon irradiation is the primary endpoint of the RCT.
Hence, PRO-GLIO has two main objectives. First, PRO-GLIO will evaluate if proton therapy is safe in patients with IDH-mutated grade II and III diffuse glioma, showing that survival figures at 2 years from radiotherapy are not poorer in the proton arm than in the photon arm. Second, we want to find the true number of patients in need of rehabilitation in both arms, and evaluate if proton therapy conveys a higher QoL than photon irradiation at 2 years from radiotherapy.
Read the detailed description
PRO-GLIO aims at establishing proton irradiation as standard radiotherapy for IDH-positive diffuse glioma grade II and III patients. First, PRO-GLIO will show that proton therapy is safe, despite the infiltrative nature of these tumors. Second, the HRQOL and neuropsychological investigating part of PRO-GLIO will show that patients irradiated with protons have a better outcome in this regard than those irradiated with photons. Inclusion criteria are a diagnosis of grade II or grade III IDH-mutated diffuse glioma, good performance status, indication for radiotherapy and age between 18 and 65 years.
Patients will be randomized to proton or photon radiotherapy and the study work will be divided in three work packages (WP).
- In WP1, survival data will be the main focus, but the estimation of QALY will also be an important part - concentrating on differences between the two study arms. If there is truly no difference between the proton and photon radiotherapy on the probability of FIFS after two years, then 224 randomized patients (112 in each treatment group) are required to be 80% certain that the upper limit of a two-sided 95% confidence interval will exclude a difference in favor of the photon radiotherapy of more than 15%. This assumes a 0.8 probability of FIFS in the control arm, and no drop-outs.
- In WP2, a battery of validated neuropsychological tests will be used to test the cognive abilities of the patients. All patients will be testes using an internet-based test (Cog-State) and 1/3 of patients will also have an in-depth neuropsychological evaluation. The two methods will be compared.
- In WP3, a battery of patient-reported outcome measures (PROMS) questionnaires will be used to establish which subjective challenges this patient group struggles the most with.
- Being tested
- Radiation therapy
- Keywords
- proton therapy, radiotherapy, IDH-mutated diffuse grade II astrocytoma, IDH-mutated diffuse grade III astrocytoma, oligodendroglioma
- Medical subject headings
- Oligodendroglioma, Astrocytoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Radiation therapyRadiation
Radiation therapy either with protons or photons
| Study group | Role | What they receive |
|---|---|---|
| Radiation therapy with protons | Experimental | Radiation therapy with protons Receives: Radiation: Radiation therapy |
| Radiation therapy with photons | Active comparator | Radiation therapy with photons at an University Hospital nearby subject's home address Receives: Radiation: Radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
First intervention free survival (FIFS) at 2 years
Survival
Measured: 2 years
Secondary outcomes (13)
Total fatigue score assessed by the fatigue questionnaire developed by T. Chalder et al.
Symptom
Measured: 2, 5, 10 and 15 years
Change in cognitive functioning (composite score from CANTAB-tests) at 2 years
Objective examination
Measured: 5 months and 2, 5, 10 and 15 years
Overall survival
Survival
Measured: Median and at 2, 5, 10 and 15 years
FIFS
Survival
Measured: Median, 5, 10 and 15 years
Progression-free survival
Survival
Measured: Median and at 2, 5, 10 and 15 years
Change in neurological function as assessed by the NANO scale
Objective examination
Measured: 2, 5, 10 and 15 years
Global cognitive impairment index
Neuropsychological endpoint
Measured: 2, 5, 10 and 15 years
Rate of local, distant and combined recurrences
Disease development
Measured: 2, 5, 10 and 15 years
Rate of patients without epileptic seizures
Symptom
Measured: 5 months and 2, 5, 10 and 15 years
EORTC QLQ C30-based algorithm score
Quality of life
Measured: 2, 5, 10 and 15 years
Incremental cost effectiveness ratio
Health economics
Measured: 2, 5, 10 and 15 years
Rate of adverse events
Toxicity
Measured: At 6 weeks, 3 and 5 months and 1 year, 2 , 5, 10 and 15 years
Costs in Norwegian kroner related to loss of production caused by disease and treatment
Health economics
Measured: 2, 5, 10 and 15 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2022
- Study start14 Jan 2022
- Primary completion31 Dec 2030 (estimated)
- Study completion31 Dec 2045 (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 OligodendrogliomaStudies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- * Experimental treatment arm with proton radiationtherapy * Standard treatment arm with photon radiationtherapy
- Masking
- None (open label)
- Enrolment
- 225 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Sahlgrenska University Hospital, The Skandion Clinic, University Hospital of North Norway, St. Olavs Hospital, Haukeland University Hospital, Lund University Hospital, Ôrebro University Hospital, Uppsala University Hospital, Karolinska University Hospital, University Hospital, Umeå, University Hospital, Linkoeping, Ryhov County Hospital
- Responsible party
- Principal investigator, Petter Brandal, Oslo University Hospital
- Investigators
- Petter Brandal, MD PhD, Principal investigator, Head of Neurooncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05190172
- Sponsor's protocol ID
- 265626
- Acronym
- PRO-GLIO
- Status last verified
- Apr 2026
- First submitted
- 15 Jul 2021
- Last updated
- 1 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: In accordance with Norwegian Data Protection Law, the dataset is only available by physical appearance at Oslo University Hospital, Norway upon request. To access data, please contact principal investigator Petter Brandal (petter.brandal@ous-hf.no). Data will not be shared before planned analyses are performed and published. The study protocol is also available upon request.
Publications
Heggebo LC, Borgen IMH, Rylander H, Kiserud C, Nordenmark TH, Hellebust TP, Evensen ME, Gustavsson M, Ramberg C, Sprauten M, Magelssen H, Blakstad H, Moorthy J, Andersson K, Raunert I, Henry T, Moe C, Granlund C, Goplen D, Brekke J, Johannessen TA, Solheim TS, Marienhagen K, Humberset O, Bergstrom P, Agrup M, Dahl L, Gubanski M, Gojon H, Brahme CJ, Ryden I, Jakola AS, Vik-Mo EO, Lie HC, Asphaug L, Hervani M, Kristensen I, Rueegg CS, Olsen IC, Ledal RJ, Degsell E, Werlenius K, Blomstrand M, Brandal P. Investigating survival, quality of life and cognition in PROton versus photon therapy for IDH-mutated diffuse grade 2 and 3 GLIOmas (PRO-GLIO): a randomised controlled trial in Norway and Sweden. BMJ Open. 2023 Mar 20;13(3):e070071. doi: 10.1136/bmjopen-2022-070071.
PubMed 36940951
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PRO-GLIO: PROton Versus Photon Therapy in IDH-mutated Diffuse Grade II and III GLIOmas
- ClinicalTrials.gov ID
- NCT05190172
- Acronym / sponsor ID
- PRO-GLIO / 265626
- Keywords
- proton therapy, radiotherapy, IDH-mutated diffuse grade II astrocytoma, IDH-mutated diffuse grade III astrocytoma, oligodendroglioma
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 225 participants (estimated)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Collaborators
- Sahlgrenska University Hospital, The Skandion Clinic, University Hospital of North Norway, St. Olavs Hospital, Haukeland University Hospital, Lund University Hospital, Ôrebro University Hospital, Uppsala University Hospital, Karolinska University Hospital, University Hospital, Umeå, University Hospital, Linkoeping, Ryhov County Hospital
- Study start
- 14 Jan 2022 (actual)
- Primary completion
- 31 Dec 2030 (estimated)
- Study completion
- 31 Dec 2045 (estimated)
- First posted
- 13 Jan 2022 (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.
Proton therapy is a powerful tool enabling oncologists to spare normal tissue around the target for irradiation much better than what can be achieved with photon irradiation. The infiltrative nature of IDH-mutated grade II and III diffuse glioma, however, renders proton therapy a potential problem. A randomized controlled trial (RCT) is the only option when trying to ensure that chances of long-term survival are not impaired seeking to reduce unwanted late treatment effects. Non-inferiority of proton therapy compared to photon irradiation is the primary endpoint of the RCT.
Hence, PRO-GLIO has two main objectives. First, PRO-GLIO will evaluate if proton therapy is safe in patients with IDH-mutated grade II and III diffuse glioma, showing that survival figures at 2 years from radiotherapy are not poorer in the proton arm than in the photon arm. Second, we want to find the true number of patients in need of rehabilitation in both arms, and evaluate if proton therapy conveys a higher QoL than photon irradiation at 2 years from radiotherapy.
Detailed description
PRO-GLIO aims at establishing proton irradiation as standard radiotherapy for IDH-positive diffuse glioma grade II and III patients. First, PRO-GLIO will show that proton therapy is safe, despite the infiltrative nature of these tumors. Second, the HRQOL and neuropsychological investigating part of PRO-GLIO will show that patients irradiated with protons have a better outcome in this regard than those irradiated with photons. Inclusion criteria are a diagnosis of grade II or grade III IDH-mutated diffuse glioma, good performance status, indication for radiotherapy and age between 18 and 65 years.
Patients will be randomized to proton or photon radiotherapy and the study work will be divided in three work packages (WP).
- In WP1, survival data will be the main focus, but the estimation of QALY will also be an important part - concentrating on differences between the two study arms. If there is truly no difference between the proton and photon radiotherapy on the probability of FIFS after two years, then 224 randomized patients (112 in each treatment group) are required to be 80% certain that the upper limit of a two-sided 95% confidence interval will exclude a difference in favor of the photon radiotherapy of more than 15%. This assumes a 0.8 probability of FIFS in the control arm, and no drop-outs.
- In WP2, a battery of validated neuropsychological tests will be used to test the cognive abilities of the patients. All patients will be testes using an internet-based test (Cog-State) and 1/3 of patients will also have an in-depth neuropsychological evaluation. The two methods will be compared.
- In WP3, a battery of patient-reported outcome measures (PROMS) questionnaires will be used to establish which subjective challenges this patient group struggles the most with.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- * Experimental treatment arm with proton radiationtherapy * Standard treatment arm with photon radiationtherapy
| Arm | Type | Receives |
|---|---|---|
| Radiation therapy with protons | Experimental | Radiation: Radiation therapyRadiation therapy with protons |
| Radiation therapy with photons | Active comparator | Radiation: Radiation therapyRadiation therapy with photons at an University Hospital nearby subject's home address |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (5 listed)
- Prior treatment (except surgery) for diffuse glioma
- Concomitant or previous malignancies. Exceptions are adequately treated basal cell carcinoma or squamous cell carcinoma of the skin, or in situ carcinoma of the cervix uteri with a follow-up time of at least 3 years, or other previous malignancy with a disease-free interval of at least 5 years
- Known CDKN2A/B homozygous deletion
- Presence of any medical, psychological, familial, sociological, or geographical characteristic that might impair patient compliance for study protocol procedures including follow-up
- Body weight > 150 kg
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 |
|---|---|---|
| Radiation therapyRadiation therapy either with protons or photons | Radiation | Radiation therapy with photons, Radiation therapy with protons |
Primary outcome
First intervention free survival (FIFS) at 2 years
Time frame: 2 years
Survival
13 secondary outcomes
Total fatigue score assessed by the fatigue questionnaire developed by T. Chalder et al.
Time frame: 2, 5, 10 and 15 years
Change in cognitive functioning (composite score from CANTAB-tests) at 2 years
Time frame: 5 months and 2, 5, 10 and 15 years
Overall survival
Time frame: Median and at 2, 5, 10 and 15 years
FIFS
Time frame: Median, 5, 10 and 15 years
Progression-free survival
Time frame: Median and at 2, 5, 10 and 15 years
Change in neurological function as assessed by the NANO scale
Time frame: 2, 5, 10 and 15 years
Global cognitive impairment index
Time frame: 2, 5, 10 and 15 years
Rate of local, distant and combined recurrences
Time frame: 2, 5, 10 and 15 years
Rate of patients without epileptic seizures
Time frame: 5 months and 2, 5, 10 and 15 years
EORTC QLQ C30-based algorithm score
Time frame: 2, 5, 10 and 15 years
Incremental cost effectiveness ratio
Time frame: 2, 5, 10 and 15 years
Rate of adverse events
Time frame: At 6 weeks, 3 and 5 months and 1 year, 2 , 5, 10 and 15 years
Costs in Norwegian kroner related to loss of production caused by disease and treatment
Time frame: 2, 5, 10 and 15 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2026.
- Derived from this study: PubMed 36940951Heggebo LC, Borgen IMH, Rylander H, Kiserud C, Nordenmark TH, Hellebust TP, Evensen ME, Gustavsson M, Ramberg C, Sprauten M, Magelssen H, Blakstad H, Moorthy J, Andersson K, Raunert I, Henry T, Moe C, Granlund C, Goplen D, Brekke J, Johannessen TA, Solheim TS, Marienhagen K, Humberset O, Bergstrom P, Agrup M, Dahl L, Gubanski M, Gojon H, Brahme CJ, Ryden I, Jakola AS, Vik-Mo EO, Lie HC, Asphaug L, Hervani M, Kristensen I, Rueegg CS, Olsen IC, Ledal RJ, Degsell E, Werlenius K, Blomstrand M, Brandal P. Investigating survival, quality of life and cognition in PROton versus photon therapy for IDH-mutated diffuse grade 2 and 3 GLIOmas (PRO-GLIO): a randomised controlled trial in Norway and Sweden. BMJ Open. 2023 Mar 20;13(3):e070071. doi: 10.1136/bmjopen-2022-070071.
- Individual participant dataSharing planned: Yes. In accordance with Norwegian Data Protection Law, the dataset is only available by physical appearance at Oslo University Hospital, Norway upon request. To access data, please contact principal investigator Petter Brandal (petter.brandal@ous-hf.no). Data will not be shared before planned analyses are performed and published. The study protocol is also available upon request.
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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.
Petter Brandal, MD PhD principal investigator
Head of Neurooncology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Radiation therapy in people with Oligodendroglioma and Oligodendroglioma, Anaplastic, run by Oslo University Hospital at 1 site in Norway.
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 0 inclusion and 5 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: looking for participants now, as of the sponsor's last update on 1 May 2026. 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 Norway. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Petter Brandal, MD PhD (+47 22934000, petter.brandal@ous-hf.no), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
First intervention free survival (FIFS) at 2 years (time frame: 2 years). 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 NCT05190172, 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 1 May 2026.