Improving Therapeutic Ratio With Hypo Fractionated Stereotactic Radiotherapy for Brain Metastases

Study Overview
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Brief Summary
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Randomized phase II trial. The study aims to investigate a different and potentially safer radio therapeutic treatment method for brain metastases. The current standard of stereotactic radiotherapy (SRT) in one or three fractions is compared to fractionated stereotactic radiotherapy (fSRT) in five fractions.

Detailed Description
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Randomized phase II trial. Stereotactic radiotherapy is one of the most frequently chosen treatment options for brain metastases. There are an increasing number of long term survivors. Brain necrosis (e.g. radio necrosis) is the most important long term side effect of the treatment, occurring in up to 40% of patients, dependent on the size of the metastasis and delivered radiotherapy dose. Retrospective studies have shown that the incidence of radio necrosis, as well as local tumor recurrence, can be decreased with a risk difference of around 20% by administrating fractionated stereotactic radiotherapy (fSRT, e.g. five fractions) over single fraction stereotactic radiotherapy, especially in large brain metastases. In this trial, one group is treated with SRT in one or three fractions. The other group is treated with fSRT in five fractions. Survival, toxicity and patient reported quality of life are monitored.

Official Title
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Improving Therapeutic Ratio With Hypo Fractionated Stereotactic Radiotherapy for Brain Metastases

Conditions
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Brain Metastases

Intervention / Treatment
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* Radiation: SRT
* Radiation: fSRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years At least one brain metastasis of large cell cancer suitable for SRT Ability to provide written informed consent- Exclusion Criteria: Contra-indication for MRI scan Primary tumor of small cell lung cancer, germinoma or lymphoma

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
Interventional Model Description: 1:1 randomization
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: SRT (stereotactic radiotherapy)<br>stereotactic radiotherapy in 1 or 3 fractions of 8 Gy up to 15-24 Gy | Radiation: SRT<br>* SRT<br>|
| Experimental: fSRT (hypo fractionated stereotactic radiotherapy)<br>hypo fractionated stereotactic radiotherapy in 5 fractions of 7 Gy up to 35 Gy. Brain stem metastases 5 fractions of 6 Gy up to 30 Gy | Radiation: fSRT<br>* fSRT<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| radio necrosis or local failure | Incidence of either radio necrosis or local failure according to Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM). | 2 years after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | median survival with Kaplan Meyer analysis | 2 years after treatment | 
| symptomatic radio necrosis (RN) or local failure (LF) | incidence of RN or LF within 2 years after SRT | 2 years after treatment | 
| salvage treatment | incidence of salvage treatment within 2 years after SRT | 2 years after treatment | 
| distant brain recurrences | incidence of distant brain recurrences within 2 years after SRT | 2 years after treatment | 
| Dose dexamethasone | Dose dexamethasone in mg per day | baseline - 2 years after treatment | 
| Anti-epileptic drug use | Anti-epileptic drug use in mg per day | baseline - 2 years after treatment | 
| Grade 2 or more toxicity (CTCAE v5.0) | incidence of Grade 2 or more toxicity according to CTCAE version 5.0 within 2 years after SRT | baseline - 2 years after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fractionated stereotactic radiotherapy