Glioblastoma Radiotherapy Using IMRT or Proton Beams

Study Overview
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Brief Summary
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Radiation therapy is an integral part of the multimodal primary therapy of glioblastomas. As the overall prognosis in this tumor entity remains unfavorable, current research is focused on additional drug therapies, which are often accompanied by increases in toxicity. By using proton beams instead of photon beams, it is possible to protect large parts of the brain which are not affected by the tumor more effectively. An initial retrospective matched-pair analysis showed that this theoretical physical benefit is also clinically associated with a reduction in toxicity during therapy and in the first few months thereafter. The aim of the GRIPS study is to prospectively test this clinical benefit in a randomized, open-label Phase III study. Patients are treated in the study using either modern photon radiation techniques (standard arm) or proton beams (experimental arm). The primary endpoint is the cumulative toxicity CTC grade 2 and higher in the first 4 months. Secondary endpoints include overall survival, progression-free survival, quality of life, and neurocognition.

Official Title
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Glioblastoma Radiotherapy Using IMRT or Proton Beams

Conditions
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Glioblastoma

Intervention / Treatment
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* Radiation: Proton irradiation
* Radiation: Photon irradiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically confirmed gliomblastoma WHO IV (operated or after biopsy) Indication for radiotherapy / radiochemotherapy Informed consent KI ≥ 60% or ECOG 0/1 Age ≥ 18 years Sufficient effective contraception Exclusion Criteria: Patient is not able to consent Previous radiotherapy in the brain or skull base Active medical implants for which there is no ion radiation authorization at the time of treatment (e.g., cardiac pacemaker, defibrillator, ...) Contraindication to MRI imaging Simultaneous participation in another clinical trial that could influence the outcome of this study or other study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Proton irradiation<br>Irradiation applied with protons | Radiation: Proton irradiation<br>* proton irradiation applied as follows: 30 x 2 Gy(RBE) 33 x 1,8 Gy (RBE), or 15 x 2,67 Gy (RBE)<br>|
| Active Comparator: Arm B: Photon IMRT<br>Photon irradiation applied as intensity-modulated radiotherapy | Radiation: Photon irradiation<br>* proton irradiation applied as follows: 30 x 2 Gy 33 x 1,8 Gy, or 15 x 2,67 Gy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative rate of toxicity | Cumulative rate of toxicity ≥ grade 2 (until progress (max. month 4)) | from start of radiotherapy until progress (max. month 4) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | Progression free survival | 1 year and 2 years | 
| Overall survival | Overall survival | 1 year and 2 years | 
| Acute Toxicity | according to CTC AE V5.0 | start of therapy until 6 weeks after end of therapy (end of therapy up to month 4) | 
| Late Toxicity | according to CTC AE V5.0 | 6 weeks after end of therapy (end of therapy up to month 4) | 
| Quality of life according to EORTC QLQ-C30 | according to EORTC QLQ-C30 | 1 year and 2 years | 
| Quality of life according to EORTC QLQ-BN20 | according to EORTC QLQ-BN20 | 1 year and 2 years | 
| Neurocognition | according to Hopkins Verbal Learning Test-Revised | 1 year and 2 years | 
| Measuring number of Lymphocytes count |  | end of therapy up to month 4 |