FIDES: Focused Ultrasound-mediated Blood-Brain Barrier Opening In Pontine Diffuse Midline Glioma (DMG) to Enhance Systemic Therapy with Temozolomide – an exploratory pilot and feasibility trial

Trial details

Who runs it

Universitair Medisch Centrum Utrecht

Trial code

EU 2025-520814-78-00

Record updated

2026. június 26.

Original description

To evaluate the safety of the Exablate-BBBO procedure and device in patients with H3K27-altered pontine DMG receiving TMZ. To determine the 6-month progression-free survival (PFS6) in patients with H3K27-altered pontine DMG treated with Exablate BBBO to TMZ maintenance therapy.Read full original descriptionShow less

To evaluate the safety of the Exablate-BBBO procedure and device in patients with H3K27-altered pontine DMG receiving TMZ. To determine the 6-month progression-free survival (PFS6) in patients with H3K27-altered pontine DMG treated with Exablate BBBO to TMZ maintenance therapy.

Inclusion: Age ≥ 4 years; 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; 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 and WHO/ECOG performance status ≤ 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 toxicities must be resolved to grade 2 prior to inclusion; If on steroids, stable or decreasing dose for at least 7 days prior to inclusion.

Exclusion: Previous or ongoing participation in other clinical trials with other than standard-of-care tumor-directed treatment(s) for H3K27-altered DMG; Treatment with anti-coagulant therapy; Expected uncontrollable therapy non-compliance/ non-cooperation that is likely to interfere with the study procedure, as per judgement of the investigators; 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; Severe hypertension, not adequately controlled with study compatible medication (Adults: RR systolic >180 and/ or RR diastolic >100; Children: >p95 + 12mmHg); History of bleeding disorder and/or coagulopathy; Known diagnosis of active or untreated hepatitis B, hepatitis C, tuberculosis; Any other illness or medical condition that in the investigator's opinion precludes participation in this study; 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; Evidence of acute clinically significant intracranial hemorrhage. NB: minimal hemorrhagic foci without obvious related clinical symptoms will not serve as grounds for exclusion; 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; Severely impaired renal function; creatinine clearance <30 mL/ min; Patient ≥ 18 years old, who requires general anesthesia to undergo the Exablate BBBO procedure; Subjects with significant liver dysfunction; Child Pugh classification C; Pregnant or lactating women; Head circumference ≤ 49 cm; Weight ≥ 135 kg; Contra-indication for MRI procedures; Known sensitivity to gadolinium-based contrast agents; Known sensitivity to the resonator agent (perflutren; Luminity®/Definity®); 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.

EU CTIS 2025-520814-78-00