Brain Tumor, Pediatric, Diffuse Glioma, Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, H3 K27M-Mutant, Pontine Tumors, Thalamic Tumor
Conditions
Brief summary
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
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.
Interventions
RADIATIONRe-irradiation
20Gy on 10 fractions
Sponsors
Aarhus University Hospital
Sahlgrenska University Hospital
Karolinska University Hospital
Radiumhospitalet, Oslo University Hospital
Rigshospitalet, Denmark
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Primary radiotherapy treatment
Eligibility
Sex/Gender
ALL
Age
12 Months to 21 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the safety of re-irradiation (reRT) | 4 weeks after end of re-irradiation | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 4 weeks after end of re-irradiation | 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. |
| Palliative efficacy measured as symptom relief | 4 weeks after end of re-irradiation | 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. |
| Other secondary outcomes | through study completion | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory analyses | through study completion | * Delineation study A comparison of variations in delineation in tumour volume among the participating institutions. This will improve the delineation-related uncertainty and, consequently, the applied margins (and hence irradiated volume) can be diminished. This will ensure a more uniform treatment across countries. * The impact of reRT on the patients and their families An analysis of the value of reRT in terms of the practical, emotional, and existential impact on patients and their families. This will be done by using a qualitative method including interviewing the parents of a subgroup of the included patients. * Referral patterns A characterisation of referral patterns of DMG patients to reRT. This will be assessed through a screenings log of all DMG patients in the participating institutions. Date of diagnosis, date of death, reRT offered yes/no, and reason for not giving reRT will be registered prospectively. |
Contacts
Primary ContactDaniella Østergaard
Backup ContactMaja V. Maraldo
Outcome results
None listed