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

Phase

N/A

Condition

Oligodendroglioma

Astrocytoma

Treatment

Radiation therapy

Clinical Study ID

NCT05190172

265626

Ages 18-65
All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Patients must be 18 to 65 years old at the day of consenting
IDH-mutated astrocytoma grade II or III, or oligodendroglioma grade II or IIIaccording to WHO 2016
Indication for radiotherapy
WHO/ECOG performance status 0-2
Ability to undergo MRI
No significant contrast enhancing tumor (more than 1 or 2 punctate contrastenhancing foci) at the time of randomization. In recurrence patients, no contrastenhancement is allowed unless a new biopsy confirms the diagnosis of IDH-mutatedastrocytoma grade 2 or 3, or oligodendroglioma grade 2 or 3.
Ability and willingness to travel to The Skandion Clinic for proton therapy ifrandomized to the proton therapy arm
Women of child-bearing potential (WOCBP) must agree to use an effective method ofcontraception during radiotherapy, chemotherapy and 1 year after completion ofchemotherapy. Pregnancy is not an ineligibility criterium if radiotherapy isindicated and cannot be postponed
Ability to understand the information about the study and included treatment andgive a written informed consent
Signed informed consent
Ability to speak and understand Norwegian or Swedish language

Exclusion

Exclusion Criteria:

Prior treatment (except surgery) for diffuse glioma
Concomitant or previous malignancies. Exceptions are adequately treated basal cellcarcinoma or squamous cell carcinoma of the skin, or in situ carcinoma of the cervixuteri with a follow-up time of at least 3 years, or other previous malignancy with adisease-free interval of at least 5 years
Known CDKN2A/B homozygous deletion
Presence of any medical, psychological, familial, sociological, or geographicalcharacteristic that might impair patient compliance for study protocol proceduresincluding follow-up
Body weight > 150 kg

Study Design

Radiation therapy

January 14, 2022

December 31, 2043

Study 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.

Connect with a study center

Oslo University Hospital
Oslo,
Norway
Active - Recruiting

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