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

Oligodendroglioma Clinical Trial

— PRO-GLIO  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05190172
• Other study ID #: 265626
• Status: Recruiting
• Phase: N/A
• Start date: January 14, 2022
• Est. completion date: December 31, 2041

Study information

• Verified date: April 2024
• Source: Oslo University Hospital
• Contact: Petter Brandal, MD PhD
• Phone: +47 22934000
• Email: petter.brandal[@]ous-hf.no
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 225
• Est. completion date: December 31, 2041
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Radiation:
• Radiation therapy
Radiation therapy either with protons or photons

Locations

Country	Name	City	State
Norway	Oslo University Hospital	Oslo

Sponsors (12)

Lead Sponsor	Collaborator
Oslo University Hospital	Haukeland University Hospital, Karolinska University Hospital, Lund University Hospital, Ôrebro University Hospital, Sahlgrenska University Hospital, Sweden, St. Olavs Hospital, The Skandion Clinic, University Hospital of North Norway, University Hospital, Linkoeping, University Hospital, Umeå, Uppsala University Hospital

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	First intervention free survival (FIFS) at 2 years	Survival	2 years
Secondary	Total fatigue score assessed by the fatigue questionnaire developed by T. Chalder et al.	Symptom	2, 5, 10 and 15 years
Secondary	Change in cognitive functioning (composite score from CANTAB-tests) at 2 years	Objective examination	5 months and 2, 5, 10 and 15 years
Secondary	Overall survival	Survival	Median and at 2, 5, 10 and 15 years
Secondary	FIFS	Survival	Median, 5, 10 and 15 years
Secondary	Progression-free survival	Survival	Median and at 2, 5, 10 and 15 years
Secondary	Change in neurological function as assessed by the NANO scale	Objective examination	2, 5, 10 and 15 years
Secondary	Global cognitive impairment index	Neuropsychological endpoint	2, 5, 10 and 15 years
Secondary	Rate of local, distant and combined recurrences	Disease development	2, 5, 10 and 15 years
Secondary	Rate of patients without epileptic seizures	Symptom	5 months and 2, 5, 10 and 15 years
Secondary	EORTC QLQ C30-based algorithm score	Quality of life	2, 5, 10 and 15 years
Secondary	Incremental cost effectiveness ratio	Health economics	2, 5, 10 and 15 years
Secondary	Rate of adverse events	Toxicity	At 6 weeks, 3 and 5 months and 1 year, 2 , 5, 10 and 15 years
Secondary	Costs in Norwegian kroner related to loss of production caused by disease and treatment	Health economics	2, 5, 10 and 15 years