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

Primary Purpose

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

Status
Recruiting
Phase
Not Applicable
Locations
Norway
Study Type
Interventional
Intervention
Radiation therapy
Sponsored by
Oslo University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Oligodendroglioma focused on measuring proton therapy, radiotherapy, IDH-mutated diffuse grade II astrocytoma, IDH-mutated diffuse grade III astrocytoma, oligodendroglioma

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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:

  11. Prior treatment (except surgery) for diffuse glioma
  12. 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
  13. More than 2 months from randomization to start radiotherapy
  14. Known CDKN2A/B homozygous deletion
  15. Presence of any medical, psychological, familial, sociological, or geographical characteristic that might impair patient compliance for study protocol procedures including follow-up

Sites / Locations

  • Oslo University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Radiation therapy with protons

Radiation therapy with photons

Arm Description

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

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

Outcomes

Primary Outcome Measures

First intervention free survival (FIFS) at 2 years
Survival

Secondary Outcome Measures

Total fatigue score assessed by the fatigue questionnaire developed by T. Chalder et al.
Symptom
Change in cognitive functioning (composite score from CANTAB-tests) at 2 years
Objective examination
Overall survival
Survival
FIFS
Survival
Progression-free survival
Survival
Change in neurological function as assessed by the NANO scale
Objective examination
Global cognitive impairment index
Neuropsychological endpoint
Rate of local, distant and combined recurrences
Disease development
Rate of patients without epileptic seizures
Symptom
EORTC QLQ C30-based algorithm score
Quality of life
Incremental cost effectiveness ratio
Health economics
Rate of adverse events
Toxicity
Costs in Norwegian kroner related to loss of production caused by disease and treatment
Health economics

Full Information

First Posted
July 15, 2021
Last Updated
February 28, 2023
Sponsor
Oslo University Hospital
Collaborators
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
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1. Study Identification

Unique Protocol Identification Number
NCT05190172
Brief Title
PRO-GLIO: PROton Versus Photon Therapy in IDH-mutated Diffuse Grade II and III GLIOmas
Acronym
PRO-GLIO
Official Title
PRO-GLIO: PROton Versus Photon Therapy in IDH-mutated Diffuse Grade II and III GLIOmas
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 14, 2022 (Actual)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
December 31, 2041 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Oslo University Hospital
Collaborators
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

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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). 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oligodendroglioma, Oligodendroglioma, Anaplastic, Diffuse Astrocytoma, IDH-Mutant
Keywords
proton therapy, radiotherapy, IDH-mutated diffuse grade II astrocytoma, IDH-mutated diffuse grade III astrocytoma, oligodendroglioma

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Experimental treatment arm with proton radiationtherapy Standard treatment arm with photon radiationtherapy
Masking
None (Open Label)
Allocation
Randomized
Enrollment
225 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Radiation therapy with protons
Arm Type
Experimental
Arm Description
Radiation therapy with protons at The Skandion Clinic, Uppsala, Sweden
Arm Title
Radiation therapy with photons
Arm Type
Active Comparator
Arm Description
Radiation therapy with photons at an University Hospital nearby subject's home address
Intervention Type
Radiation
Intervention Name(s)
Radiation therapy
Intervention Description
Radiation therapy either with protons or photons
Primary Outcome Measure Information:
Title
First intervention free survival (FIFS) at 2 years
Description
Survival
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Total fatigue score assessed by the fatigue questionnaire developed by T. Chalder et al.
Description
Symptom
Time Frame
2, 5, 10 and 15 years
Title
Change in cognitive functioning (composite score from CANTAB-tests) at 2 years
Description
Objective examination
Time Frame
5 months and 2, 5, 10 and 15 years
Title
Overall survival
Description
Survival
Time Frame
Median and at 2, 5, 10 and 15 years
Title
FIFS
Description
Survival
Time Frame
Median, 5, 10 and 15 years
Title
Progression-free survival
Description
Survival
Time Frame
Median and at 2, 5, 10 and 15 years
Title
Change in neurological function as assessed by the NANO scale
Description
Objective examination
Time Frame
2, 5, 10 and 15 years
Title
Global cognitive impairment index
Description
Neuropsychological endpoint
Time Frame
2, 5, 10 and 15 years
Title
Rate of local, distant and combined recurrences
Description
Disease development
Time Frame
2, 5, 10 and 15 years
Title
Rate of patients without epileptic seizures
Description
Symptom
Time Frame
5 months and 2, 5, 10 and 15 years
Title
EORTC QLQ C30-based algorithm score
Description
Quality of life
Time Frame
2, 5, 10 and 15 years
Title
Incremental cost effectiveness ratio
Description
Health economics
Time Frame
2, 5, 10 and 15 years
Title
Rate of adverse events
Description
Toxicity
Time Frame
At 6 weeks, 3 and 5 months and 1 year, 2 , 5, 10 and 15 years
Title
Costs in Norwegian kroner related to loss of production caused by disease and treatment
Description
Health economics
Time Frame
2, 5, 10 and 15 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 III according to WHO 2016 Indication for radiotherapy WHO/ECOG performance status 0-2 Ability to undergo MRI 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. Ability and willingness to travel to The Skandion Clinic for proton therapy if randomized to the proton therapy arm 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 Ability to understand the information about the study and included treatment and give a written informed consent Signed informed consent Ability to speak and understand Norwegian or Swedish language Exclusion Criteria: Prior treatment (except surgery) for diffuse glioma 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 More than 2 months from randomization to start radiotherapy Known CDKN2A/B homozygous deletion Presence of any medical, psychological, familial, sociological, or geographical characteristic that might impair patient compliance for study protocol procedures including follow-up Body weight > 150 kg
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Petter Brandal, MD PhD
Phone
+47 22934000
Email
petter.brandal@ous-hf.no
First Name & Middle Initial & Last Name or Official Title & Degree
Carin Granlund
Phone
+4722934000
Email
carvan@ous-hf.no
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Petter Brandal, MD PhD
Organizational Affiliation
Head of Neurooncology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Oslo University Hospital
City
Oslo
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Petter Brandal, MD Phd
Phone
+47 22935843
Email
pebra@ous-hf.no

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
In accordance with Norwegian Data Protection Law, the dataset is only available by physical appearance at Oslo University Hospital, Norway upon request. To access data, please contact principal investigator Petter Brandal (petter.brandal@ous-hf.no). Data will not be shared before planned analyses are performed and published. The study protocol is also available upon request.
IPD Sharing Time Frame
Data will be available following publication of the primary and key secondary endpoints. The study protocol is available upon request from this date
IPD Sharing Access Criteria
Physical appearance at Oslo University Hospital, Norway.

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

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