Proton vs. Photon Radiotherapy for Patients With WHO Grade 2-3 Glioma

NCT07750457 | Recruiting DMC

• 1 other identifier: EXT-201613_GliProPh
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

Patients with grade 2 and 3 gliomas who received photon radiation therapy as part of their standard treatment are at risk of developing cognitive impairments, depending on the tumor's location and the size of the target volume. The extent to which these are caused in individual cases by the brain tissue within the target volume, which is necessarily exposed to a high dose, or whether they can be modified by differences in the exposure of surrounding brain regions exposed to low or moderate doses, is unknown. With the help of proton therapy, the risk of neurocognitive dysfunction could potentially be reduced by decreasing the brain volumes outside the target volume that are exposed to radiation therapy and receive a low dose. Based on current knowledge of relative biological effectiveness, the efficacy of proton therapy on the tumor compared to photon therapy can be considered equivalent with lower levels of uncertainty. In the present study, the impact of photon irradiation versus proton irradiation on neurocognition will now be directly compared. A bicentric, randomized study will investigate whether treating patients with WHO Grade 2 and 3 gliomas with proton radiation results in a different temporal course of neurocognitive function after treatment compared to photon radiation therapy.

Conditions

Glioma

Keywords

glioma; photon therapy; proton therapy; neurocognitive function

Outcome Measures

Primary Outcomes (1)

• Neurocognition

  Composite Z-Score (Neurocognition) based on the cognitive domains assessed 3 years after completion of radiation therapy

  three years after finishing radiotherapy

Secondary Outcomes (9)

• Neurocognition

  4 weeks and 1, 2, 4, 5, and 6 years after completion of radiation therapy

• Decline of cognitive domains

  At 4 weeks and 1, 2, 3, 4, 5, and 6 years after completion of radiation therapy

• Quality of Life

  Pre radiation until 6 years after finishing radiotherapy

• Quality of Life

  Pre radiation until 6 years after finishing radiotherapy

• Overall survival

  From beginning until progression/death

Study Arms (2)

Photon therapy

ACTIVE COMPARATOR

Grade 2 gliomas: 5 × 1.8 GyRBE to a total of 54 GyRBE Grade 3 gliomas: 5 × 1.8 GyRBE to a total of 59.4 GyRBE (with concurrent chemotherapy) or 5 × 2.0 GyRBE to a total of 60 GyRBE

Radiation: Photon therapy

Proton therapy

EXPERIMENTAL

Grade 2 gliomas: 5 × 1.8 GyRBE to a total of 54 GyRBE Grade 3 gliomas: 5 × 1.8 GyRBE to a total of 59.4 GyRBE (with concurrent chemotherapy) or 5 × 2.0 GyRBE to a total of 60 GyRBE

Radiation: Proton therapy

Interventions

Proton therapy RADIATION

Grade 2 gliomas: 5 × 1.8 GyRBE to a total of 54 GyRBE Grade 3 gliomas: 5 × 1.8 GyRBE to a total of 59.4 GyRBE (with concurrent chemotherapy) or 5 × 2.0 GyRBE to a total of 60 GyRBE

Proton therapy

Photon therapy RADIATION

Grade 2 gliomas: 5 × 1.8 GyRBE to a total of 54 GyRBE Grade 3 gliomas: 5 × 1.8 GyRBE to a total of 59.4 GyRBE (with concurrent chemotherapy) or 5 × 2.0 GyRBE to a total of 60 GyRBE

Photon therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Histologically confirmed IDH-mutated WHO Grade 2 or 3 glioma with an indication for radiation therapy as determined by the local tumorboard at the study center
• \. Tumor classification according to the 2021 WHO Classification, including the presence of the following markers:
• IDH1/2 mutation
• ATRX and/or 1p19q codeletion status
• CDKN2A/B codeletion status
• \. A Karnofsky Performance Status of ≥ 70%
• \. Patients must be ≥ 18 years of age
• \. Radiation therapy must begin within 7 weeks of surgery in patients with CNS WHO Grade 2 IDH-mutated gliomas. In individual cases, the start may be delayed, but not later than 10 weeks after surgery
• \. For patients with WHO Grade 2 IDH-mutated CNS gliomas, the following applies:
• There is an indication for radiation therapy (partial tumor resection, age \> 40 years, relevant neurological deficit)
• Enrollment in the study at the time of tumor progression is possible, even without a time constraint relative to the initial surgery, if the following criteria are met:
• There was initially no indication for radiation therapy
• At the time of tumor progression, there is an indication for radiation therapy as determined by the local tumor board
• Radiation therapy must begin within 7 weeks after the recurrence MRI (or surgery, if a repeat surgery has been performed). In individual cases, treatment may begin later, but no later than 10 weeks after the recurrence MRI/surgery
• \. For patients with WHO Grade 3 IDH-mutated CNS gliomas, radiation therapy must begin within 7 weeks after surgery . In individual cases, treatment may begin later, but no later than 10 weeks after surgery

You may not qualify if:

• \. Concurrent participation in another clinical interventional study or participation in a clinical study that requires administration of an investigational drug within 30 days prior to study enrollment.
• \. A physical or mental condition of the patient that, in the judgment of the study physician, could endanger the patient, could bias the study results, or could negatively affect the patient's participation in the clinical trial.
• \. Known or ongoing abuse of drugs, alcohol, or medications.
• \. At the time of tumor recurrence in patients with WHO Grade 2 IDH-mutated CNS gliomas, there is evidence on MRI of malignancy (e.g., marked contrast enhancement indicating Grade 3-4).
• \. Previous radiation therapy to the head or head and neck region
• \. Previous chemotherapy due to a CNS neoplasm
• \. Severe comorbidities that limit compliance with study requirements
• \. Malignant invasive tumor disease with a tumor-free period of \< 3 years
• \. Evidence of leptomeningeal dissemination
• \. Spinal or infratentorial tumor location
• \. Patients with a known infection with the human immunodeficiency virus (HIV)
• \. Patients with a newly diagnosed hepatitis infection or-at the discretion of the responsible study physician-a significant risk of reactivation

Sponsors & Collaborators

• University Hospital, Essen: lead
• University Hospital Giessen and Marburg: collaborator

Study Sites (2)

Universitätsklinikum Essen

Essen, Germany

RECRUITING

Universitätsklinikum Gießen und Marburg

Giessen, Germany

RECRUITING

MeSH Terms

Conditions

Glioma

Interventions

Proton Therapy

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Heavy Ion Radiotherapy; Radiotherapy; Therapeutics

Central Study Contacts

Sied Kebir, PD Dr med.

CONTACT

+492017230; neuroonkologie@uk-essen.de

Christoph Oster, Dr. med.

CONTACT

+492017230; neuroonkologie@uk-essen.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PD Dr. med. Sied Kebir, Prof. Dr. Martin Stuschke und Prof. Dr. Beate Timmermann

Model Details: randomized in two arms: Proton vs. photon therapy. Chemotherapy according to local standard (sequential temozolomide or procarbazine/CCNU).

Study Record Dates

• First Submitted: July 29, 2026
• First Posted: August 6, 2026
• Study Start: January 15, 2019
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2033
• Last Updated: August 6, 2026

Record last verified: 2026-08

Locations

DE (2)