PRO-GLIO: PROton Versus Photon Therapy in IDH-mutated Diffuse Grade II and III GLIOmas

NCT ID: NCT05190172

Last Updated: 2025-02-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 225 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-14
• Study Completion Date: 2043-12-31

Brief 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. 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).

1. 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.

2. 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.

3. 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.

Conditions

Oligodendroglioma; Oligodendroglioma, Anaplastic; Diffuse Astrocytoma, IDH-Mutant

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Radiation therapy with protons

Radiation therapy with protons at The Skandion Clinic, Uppsala, Sweden

Group Type: EXPERIMENTAL

Radiation therapy

Intervention Type: RADIATION

Radiation therapy either with protons or photons

Radiation therapy with photons

Radiation therapy with photons at an University Hospital nearby subject's home address

Group Type: ACTIVE_COMPARATOR

Radiation therapy

Intervention Type: RADIATION

Radiation therapy either with protons or photons

Interventions

Radiation therapy

Radiation therapy either with protons or photons

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

1. Patients must be 18 to 65 years old at the day of consenting

2. IDH-mutated astrocytoma grade II or III, or oligodendroglioma grade II or III according to WHO 2016

3. Indication for radiotherapy

4. WHO/ECOG performance status 0-2

5. Ability to undergo MRI

6. No significant contrast enhancing tumor (more than 1 or 2 punctate contrast enhancing foci) at the time of randomization. In recurrence patients, no contrast enhancement is allowed unless a new biopsy confirms the diagnosis of IDH-mutated astrocytoma grade 2 or 3, or oligodendroglioma grade 2 or 3.

7. Ability and willingness to travel to The Skandion Clinic for proton therapy if randomized to the proton therapy arm

8. Women of child-bearing potential (WOCBP) must agree to use an effective method of contraception during radiotherapy, chemotherapy and 1 year after completion of chemotherapy. Pregnancy is not an ineligibility criterium if radiotherapy is indicated and cannot be postponed

9. Ability to understand the information about the study and included treatment and give a written informed consent

10. Signed informed consent

11. Ability to speak and understand Norwegian or Swedish language

Exclusion Criteria

1. Prior treatment (except surgery) for diffuse glioma

2. 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

3. Known CDKN2A/B homozygous deletion

4. Presence of any medical, psychological, familial, sociological, or geographical characteristic that might impair patient compliance for study protocol procedures including follow-up

5. Body weight > 150 kg

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sahlgrenska University Hospital

OTHER

Sponsor Role: collaborator

The Skandion Clinic

UNKNOWN

Sponsor Role: collaborator

University Hospital of North Norway

OTHER

Sponsor Role: collaborator

St. Olavs Hospital

OTHER

Sponsor Role: collaborator

Haukeland University Hospital

OTHER

Sponsor Role: collaborator

Lund University Hospital

OTHER

Sponsor Role: collaborator

Ôrebro University Hospital

UNKNOWN

Sponsor Role: collaborator

Uppsala University Hospital

OTHER

Sponsor Role: collaborator

Karolinska University Hospital

OTHER

Sponsor Role: collaborator

University Hospital, Umeå

OTHER

Sponsor Role: collaborator

University Hospital, Linkoeping

OTHER

Sponsor Role: collaborator

Jönköping University Hospital

UNKNOWN

Sponsor Role: collaborator

Oslo University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Petter Brandal

Head of Neurooncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Petter Brandal, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Head of Neurooncology

Locations

Oslo University Hospital

Oslo, , Norway

Site Status: RECRUITING

Countries

Norway

Central Contacts

Petter Brandal, MD PhD

Role: CONTACT

petter.brandal@ous-hf.no

+47 22934000

Carin Granlund

Role: CONTACT

carvan@ous-hf.no

+4722934000

Facility Contacts

Petter Brandal, MD Phd

Role: primary

pebra@ous-hf.no

+47 22935843

References

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.

Reference Type: DERIVED

PMID: 36940951 (View on PubMed)

Other Identifiers

265626

Identifier Type: -

Identifier Source: org_study_id