Diffuse Midline Glioma
Conditions
Interventions
Six cycles of TMZ maintenance therapy will be combined with MRI-guided Exablate BBBO on the first day of each cycle. One cycle consists of 5 consecutive days of oral TMZ, followed by 23 days of rest.
Sponsors
Universitair Medisch Centrum Utrecht
Eligibility
Age
2 Years to 99 Years
Inclusion criteria
Inclusion criteria: Age = 4 years. Histologically/molecularly verified de novo pontine H3K27-altered diffuse midline glioma.Main localization (‘center of mass’) in the brainstem. NB: some degree of extension beyond the brainstem, e.g. cerebellar peduncles, is allowed.Karnofsky Performance Score (KPS) or Lansky Performance Score (LPS) of = 70/ KPS or LPS 60-69 and WHO = 2.ASA-score of I-III. Intention to treat with (TMZ chemo-) radiation and maintenance TMZ as per consensus of the local multidisciplinary tumor board.Feasible to schedule the first Exablate BBBO procedure preferably within 4-6 weeks, acceptably within 12 weeks after successful completion of radiotherapy/ concomitant TMZ-chemoradiation, defined as: completed treatment as planned without reported CTCAEv6.0 grade 3-4 toxicities or, in case of reported CTCAEv6.0 grade 3-4 toxicities, the toxicitis must be resolved to grade 2 prior to inclusion.If on steroids, stable or decreasing dose for at least 7 days prior to inclusion.Able to attend all study visits.Able and willing to give informed consent or have a legal guardian who is able and willing to do so.
Exclusion criteria
Exclusion criteria: Previous or ongoing participation in other clinical trials with other than standard-of-care tumor-directed treatment(s) for H3K27-altered DMG.Multifocal or leptomeningeal metastasized disease. Multifocal disease is defined as multiple FLAIR-hyperintense lesions, separated by normal-appearing brain tissue, with or without gadolinium enhancement. Multiple enhancing regions within one continuous FLAIR lesion can be considered as unifocal disease. Signs/symptoms of elevated intracranial pressure (ICP) (e.g. headache, vomiting, impaired vision/papilledema, impaired consciousness), with corresponding radiographic findings on MRI at time of screening. Severe dysphagia with feeding tube dependency.Evidence of acute clinically significant intracranial hemorrhage. NB: minimal hemorrhagic foci without obvious related clinical symptoms will not serve as grounds for exclusion. Tumor not visible on any pre-therapy or post-radiation imaging.Presence of extracranial / intracranial structures (e.g. metal prostheses, implants, calcifications) on pre-treatment CT-scan/ MRI-scan, significantly interfering with acoustic impedance as per judgement of the researchers.Known co-occurring other malignancy that is progressing or has required active treatment within the past 3 years, with exception of: carcinomas in situ (CIS) and non-melanoma skin cancers. Patients with right-to-left, bi-directional or transient right-to-left cardiac shunts.Known LVEF < 40 or unstable hemodynamics.Severe hypertension, not adequately controlled with medication (Adults: RR systolic >180 and/ or RR diastolic >100; Children: >p95+12mmHg).History of bleeding disorder and/or coagulopathy.Treatment with anti-coagulant therapy.Severely impaired renal function; creatinine clearance <30 mL/ min.Subjects with significant liver dysfunction; Child Pugh classification C.Known diagnosis of active or untreated hepatitis B, hepatitis C, tuberculosis.Any illness or medical condition that in the investigator's opinion precludes participation in this study.Pregnant or lactating women.Expected uncontrollable therapy non-compliance/ non-cooperation that is likely to interfere with the study procedure, as per judgement of the investigators.Head circumference = 49 cm.Weight = 135 kg.Patient = 18 years old, who requires general anesthesia to undergo the Exablate BBBO procedure.Contra-indication for MRI procedures.Known sensitivity to gadolinium-based contrast agents.Known sensitivity to the resonator agent (perflutren; Luminity®).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoints are device and procedure-related safety and progression-free survival at 6 months. Safety will be evaluated through physical examination, laboratory exams and radiological assessments with MRI during both treatment and follow-up. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints are feasibility and efficacy-related outcome measures, including progression-free survival (PFS), response rate and overall survival (OS). For the secondary outcome measures, we will compare study participants to matched cases from historical cohorts/registries (e.g. the SIOPE DIPG Registry, International DIPG/DMG Registry and national DMG cohorts). | — |
Countries
Netherlands
Contacts
Public ContactT.J. Snijders
Universitair Medisch Centrum Utrecht
Outcome results
None listed