RE-irradiation of Diffuse MIdline Glioma paTients

Study Overview
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Brief Summary
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The REMIT (RE-irradiation of diffuse MIdline glioma paTients) study evaluates safety and the palliative efficacy of re-irradiation of patients with diffuse midline glioma (DMG). The study will introduce a standard re-irradiation treatment schedule for DMG patients who have progressed following primary treatment.

Detailed Description
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REMIT is a non-randomized, prospective, investigator-initiated, phase II, multi-centre observational study with two inclusion groups, arm A and B. Arm A and B will be offered the same treatment. Patients treated with primary radiotherapy 54Gy/30 fractions, either enrolled in the BIOMEDE 2.0 protocol or not, will be included in Arm A. DMG patients treated with any other total dose and fractionation than 54Gy/30F will be included in Arm B. The re-RT and follow up will be the same in both arms. As treatment 20Gy/10 fractions is given as first time re-irradiation with extended follow up on toxicity, performance status and quality of life.

Official Title
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RE-irradiation of Diffuse MIdline Glioma paTients

Conditions
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Diffuse Midline Glioma, H3 K27M-Mutant, Diffuse Intrinsic Pontine Glioma, Diffuse Glioma, Pontine Tumors, Thalamic Tumor, Brain Tumor, Pediatric

Intervention / Treatment
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* Radiation: Re-irradiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diffuse midline glioma diagnosis: verified radiologically or histologically Biopsy is not mandatory for REMIT Age ≥ 12 months to ≤21 years. Min. 180 days/6 months have elapsed from the first day of the 1st RT course 1st course of radiotherapy Full recovery from all acute and subacute toxicities of 1st RT course Clinical progression of symptoms and/or radiographic progression Karnofsky performance status scale or Lansky Play Scale > 50% The performance status should not take the neurological deficits per se into account. NB: Children and adults with a worsening performance status due to glioma-related motor deficit can be included. Life expectancy > 12 weeks after start of reRT Signed informed consent by patient and/or parents or legal guardian Exclusion Criteria: Presence of leptomeningeal spread or multifocal disease on MRI at progression Other co-morbidity that according to the treating physician would impair participation in the study >1 course of radiotherapy Neurofibromatosis type 1 Inability to complete the medical follow-up (geographic, social, or mental reasons)

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 21 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 |
| --- | --- |
| Other: A<br>Primary radiotherapy 54Gy/30 fractions | Radiation: Re-irradiation<br>* 20Gy on 10 fractions<br>|
| Other: B<br>Any other dose and fractionation for primary radiotherapy than 54gy/30 fractions. | Radiation: Re-irradiation<br>* 20Gy on 10 fractions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety of re-irradiation (reRT) | The primary endpoint will be the cumulative incidence of grade ≥4 CTCAE (The NCI Common Terminology Criteria for Adverse Events) events measured 4 weeks after the last day of reRT. | 4 weeks after end of re-irradiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The key secondary objective is to prospectively validate the palliative efficacy of reRT of DMG. Palliative efficacy is evaluated by two endpoints: overall survival and symptom relief. | Palliative efficacy measured as overall survival will be reported as 1) from date of diagnosis to date of death by any cause, and 2) from date of first radiological and/or clinical progression to date of death by any cause. | 4 weeks after end of re-irradiation | 
| Palliative efficacy measured as symptom relief | Symptom relief measured by 1) clinical performance status (Karnofsky or Lansky) assessed every second week, 2) a modified PEDI score before, during and 4 weeks after reRT, 3) steroid dose levels measured every second week, and 4) quality of life monitored before, during and 4 weeks after re-irradiation with PedsQL Cancer module questionnaire. | 4 weeks after end of re-irradiation | 
| Other secondary outcomes | Other secondary objectives are further defined as: Image-guided characterization of the anatomical site of progression compared to the primary lesion. Assessment of cumulated radiation dose to critical structures in the brain following the initial and reRT treatment. | through study completion |