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

Sponsor
Oslo University Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT05190172
Collaborator
Sahlgrenska University Hospital, Sweden (Other), The Skandion Clinic (Other), University Hospital of North Norway (Other), St. Olavs Hospital (Other), Haukeland University Hospital (Other), Lund University Hospital (Other), Ôrebro University Hospital (Other), Uppsala University Hospital (Other), Karolinska University Hospital (Other), University Hospital, Umeå (Other), University Hospital, Linkoeping (Other)
225
Enrollment
1
Location
2
Arms
239.5
Anticipated Duration (Months)
0.9
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or DiseaseIntervention/TreatmentPhase
  • Radiation: Radiation therapy
N/A

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
225 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Experimental treatment arm with proton radiationtherapy Standard treatment arm with photon radiationtherapyExperimental treatment arm with proton radiationtherapy Standard treatment arm with photon radiationtherapy
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
PRO-GLIO: PROton Versus Photon Therapy in IDH-mutated Diffuse Grade II and III GLIOmas
Actual Study Start Date :
Jan 14, 2022
Anticipated Primary Completion Date :
Dec 31, 2025
Anticipated Study Completion Date :
Dec 31, 2041

Arms and Interventions

ArmIntervention/Treatment
Experimental: Radiation therapy with protons

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

Radiation: Radiation therapy
Radiation therapy either with protons or photons

Active Comparator: Radiation therapy with photons

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

Radiation: Radiation therapy
Radiation therapy either with protons or photons

Outcome Measures

Primary Outcome Measures

  1. First intervention free survival (FIFS) at 2 years [2 years]

    Survival

Secondary Outcome Measures

  1. Total fatigue score assessed by the fatigue questionnaire developed by T. Chalder et al. [2, 5, 10 and 15 years]

    Symptom

  2. Planning working memory raw scores as assessed by the CANTAB Connect battery [5 months and 2, 5, 10 and 15 years]

    Objective examination

  3. Overall survival [Median and at 2, 5, 10 and 15 years]

    Survival

  4. FIFS [5, 10 and 15 years]

    Survival

  5. Median progression-free survival [Through study completion, approximately 15 years]

    Survival

  6. Change in neurological function as assessed by the NANO scale [2, 5, 10 and 15 years]

    Objective examination

  7. Global cognitive impairment index [2, 5, 10 and 15 years]

    Neuropsychological endpoint

  8. Rate of local, distant and combined recurrences [2, 5, 10 and 15 years]

    Disease development

  9. Rate of patients without epileptic seizures [5 months and 2, 5, 10 and 15 years]

    Symptom

  10. EORTC QLQ C30-based algorithm score [2, 5, 10 and 15 years]

    Quality of life

  11. Incremental cost effectiveness ratio [2, 5, 10 and 15 years]

    Health economics

  12. Rate of adverse events [At 6 weeks, 3 and 5 months and 1 year, 2 , 5, 10 and 15 years]

    Toxicity

  13. Costs in Norwegian kroner related to loss of production caused by disease and treatment [2, 5, 10 and 15 years]

    Health economics

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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. Available MRI not older than 2 months at study inclusion, preferably including volumetric FLAIR-imaging

  6. No significant contrast enhancing tumor at the time of randomization

  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

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

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Oslo University HospitalOsloNorway

Sponsors and Collaborators

  • Oslo University Hospital
  • Sahlgrenska University Hospital, Sweden
  • 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

Investigators

  • Principal Investigator: Petter Brandal, MD PhD, Head of Neurooncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Petter Brandal, Head of Neurooncology, Oslo University Hospital
ClinicalTrials.gov Identifier:
NCT05190172
Other Study ID Numbers:
  • 265626
First Posted:
Jan 13, 2022
Last Update Posted:
Jan 18, 2022
Last Verified:
Jan 1, 2022
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Petter Brandal, Head of Neurooncology, Oslo University Hospital
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jan 18, 2022