Comparison of Proton and Photon Radiotherapy of Brain Tumors (ProtoChoice-Hirn)

Study Overview
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Brief Summary
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This protocol compares the toxicity of radiotherapy or radiochemotherapy applied with different radiation modalities - protons or photons. Patients with different kinds of brain tumours and foreseen high-dose radiotherapy can be included. The hypothesis of the trial is that the rate of chronic toxicity 1 year after the end of radiotherapy is 15% lower after proton compared to photon treatment.

Detailed Description
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Non-randomised 2-arm phase II trial on comparison of proton versus photon radiotherapy in brain tumours using standard doses and standard combined chemotherapy protocols. Patients are assigned to the treatment groups by their own choice or availability of the treatment. Patients are stratified into 4 groups, (1) supratentorial grad III/ IV tumours without pre-irradiation; (2) supratentorial grade I/II tumours without pre-irradiation; (3) infratentorial tumours without pre-irradiation; (4) patients with pre-irradiation >40 Gy in the tumour area. Radiotherapy doses of 54-60 Gy(RBE) are applied in group 1-3 using normal fractionated schedules. In group 4, 30 Gy(RBE)/ 5 Gy(RBE) per fraction or 36 Gy(RBE) with 2 Gy(RBE) per fraction are allowed. Primary endpoint is chronic toxicity and quality of life. The hypothesis of the trial is that the rate of chronic toxicity 1 year after the end of radiotherapy is 15% lower after proton compared to photon treatment. Events for chronic toxicity are toxicities observed later than 3 months after end of radiotherapy and scored CTC-AE4.0 >grade 2 or a decrease in Quality of life by >10% (EORTC-QLQ C30 and BN20) or a decrease in neuropsychological functioning by >10% (MoCa test). All statistical calculations apply to group (1), i.e. supratentorial grade II/IV tumours without pre-irradiation, all other arms are closed when group (1) is closed.

Official Title
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Comparison of Proton and Photon Radiotherapy of Brain Tumors: Efficiency and Side Effects in Clinical Standard Doses

Conditions
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Brain Tumors

Intervention / Treatment
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* Radiation: Radiation with protons
* Radiation: Radiation with photons


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: primary brain tumor: gliomas (low or high grade), intracerebral meningiomas, pituitary adenomas, craniopharyngioma and other rare brain tumors brain tumor recurrence without pre-irradiation brain tumor recurrence with pre-irradiation > 40 Gy in the overlap region with the recurrence region indication for radiotherapy or radiochemotherapy Both proton and photon therapy are possible from a medical point of view (that is no standard indication for protons or standard indication for example one-time stereotaxy age >= 18 years general condition ECOG ≤ 2, outpatient basis possible indication for high dose (except group 4) radiotherapy or radiochemotherapy capacity to consent and present written informed consent Exclusion Criteria: lack of capacity to consent or lack of written consent cerebral lymphomas brain metastases very small tumors (for example acoustic neuromas, very small recurrences) for this is a proton therapy from a medical point of view no alternative to a stereotactic radiotherapy inability to MRI planning (eg. contraindications to performing MRI) lack of compliance of the patient lack of or limited possibility of a reproducible storage (eg by severe restriction of mobility of the patient) missing or limited possibility of regular follow-up visits in accordance with the study protocol

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: supratentorial, grade III/IV, photon<br>Radiation with photons normofractionated 54-60 Gy. Not pre-irradiated patients. | Radiation: Radiation with photons<br> <br> |
| Experimental: supratentorial, grade III/IV, proton<br>Radiation with protons normofractionated 54-60 Gy(RBE). Not pre-irradiated patients. | Radiation: Radiation with protons<br> <br> |
| Active Comparator: supratentorial, grade I/II, photon<br>Radiation with photons normofractionated 54-60 Gy. Not pre-irradiated patients, bening tumors. | Radiation: Radiation with photons<br> <br> |
| Experimental: supratentorial, grade I/II, proton<br>Radiation with protons normofractionated 54-60 Gy(RBE). Not pre-irradiated patients, bening tumors. | Radiation: Radiation with protons<br> <br> |
| Active Comparator: infratentorial, photon<br>Radiation with photons normofractionated 54-60 Gy. Not pre-irradiated patients. | Radiation: Radiation with photons<br> <br> |
| Experimental: infratentorial, proton<br>Radiation with protons normofractionated 54-60 Gy(RBE). Not pre-irradiated patients. | Radiation: Radiation with protons<br> <br> |
| Active Comparator: pre-radiation, photon<br>> 40Gy in the region of recurrence. Radiation with photons normofractionated 54-60 Gy(RBE) or 5 Gy(RBE)/fraction until 30 Gy(RBE) or normofractionated 36 Gy(RBE). | Radiation: Radiation with photons<br> <br> |
| Experimental: pre-radiation, proton<br>> 40Gy in the region of recurrence. Radiation with protons normofractionated 54-60 Gy(RBE) or 5 Gy(RBE)/fraction until 30 Gy(RBE) or normofractionated 36 Gy(RBE). | Radiation: Radiation with protons<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| late toxicity as cumulative measure | Events for the endpoint are: any late toxicity CTCAE 4.0 ≥ grade II (except pre-existing conditions) decrease in Quality of life (EORTC-QLQ-C30 and BN20) by >10% decrease in brain function (MOCA test) by more than 10% | 1 year (or at least 6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local tumour control | Local tumour control as Regression or stable disease measured in follow-up MRI | 1 year and 2 years | 
| Overall survival | Overall survival | 1 year and 2 years | 
| Acute toxicity | Acute toxicity according to CTCAE4.0 score >/= grade II | 3 months after treatment | 
| late toxicity as cumulative measure | Events for the endpoint are: any late toxicity CTCAE 4.0 ≥ grade II (except pre-existing conditions) decrease in Quality of life (EORTC-QLQ-C30 and BN20) by >10% decrease in brain function (MOCA test) by more than 10% | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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brain tumors, proton radiotherapy, photon radiotherapy