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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years - 65 Years
Gender	All

More Inclusion & Exclusion 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 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. More than 2 months from randomization to start radiotherapy. 4. Known CDKN2A/B homozygous deletion. 5. Presence of any medical, psychological, familial, sociological, or geographical characteristic that might impair patient compliance for study protocol procedures including follow-up. 6. Body weight > 150 kg

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05190172
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	N/A
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Oslo University Hospital
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Petter Brandal, MD PhD
Principal Investigator Affiliation	Head of Neurooncology
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	Norway
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Oligodendroglioma, Oligodendroglioma, Anaplastic, Diffuse Astrocytoma, IDH-Mutant

Additional Details

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.

Arms & Interventions

Arms

Experimental: Radiation therapy with protons

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

Active Comparator: Radiation therapy with photons

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

Interventions

Radiation: - Radiation therapy

Radiation therapy either with protons or photons

Contact a Trial Team

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International Sites

Oslo University Hospital, Oslo, Norway

Status

Recruiting

Address

Oslo University Hospital

Oslo, ,

Site Contact

Petter Brandal, MD Phd

[email protected]

+47 22935843

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