RE-irradiation of Diffuse MIdline Glioma paTients (REMIT)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Diffuse Intrinsic Pontine Glioma; Diffuse Midline Glioma, H3 K27M-Mutant; Diffuse Glioma; Pontine Tumors; Brain Tumor, Pediatric; Thalamic Tumor
• Intervention / Treatment: Radiation: Re-irradiation

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.

• Study Type: Interventional
• Enrollment (Estimated): 59
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Daniella Østergaard; Phone Number: +4520822297; Email: daniella.elisabet.oestergaard.01@regionh.dk
• Study Contact Backup: Name: Maja V. Maraldo; Phone Number: +4535451117; Email: Maja.Vestmoe.Maraldo@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: A; Primary radiotherapy 54Gy/30 fractions	Radiation: Re-irradiation; 20Gy on 10 fractions
Other: B; Any other dose and fractionation for primary radiotherapy than 54gy/30 fractions.	Radiation: Re-irradiation; 20Gy on 10 fractions

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory analyses	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.	through study completion

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Collaborators: Karolinska University Hospital; Aarhus University Hospital; Sahlgrenska University Hospital, Sweden; Radiumhospitalet, Oslo University Hospital
• Investigators: Principal Investigator: Maja V Maraldo, Department of oncology and radiotherapy, Copenhagen University Hospital Rigshospitalet

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): November 1, 2029
• Study Completion (Estimated): November 1, 2029

Study Registration Dates

• First Submitted: September 8, 2023
• First Submitted That Met QC Criteria: October 16, 2023
• First Posted (Actual): October 23, 2023

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 16, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Infratentorial Neoplasms; Glioma; Diffuse Intrinsic Pontine Glioma; Brain Stem Neoplasms
• Other Study ID Numbers: REMIT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All data will be collected in a RedCap database.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No