TEMOZOLOMIDE for Diffuse Midline Glioma, H3K27-altered

Inclusion criteria

• {"criterion_text":"- Age ≥ 4 years.\n- Able to attend all study visits.\n- Able and willing to give informed consent or have a legal guardian who is able and willing to do so.\n- Histologically/molecularly verified de novo pontine H3K27-altered diffuse midline glioma.\n- Main localization (‘center of mass’) in the brainstem. NB: some degree of extension beyond the brainstem, e.g. cerebellar peduncles, is allowed.\n- Karnofsky Performance Score (KPS) or Lansky Performance Score (LPS) of ≥ 70/ KPS or LPS 60 and WHO/ECOG performance status ≤ 2.\n- ASA-score of I-III.\n- Intention to treat with (TMZ chemo-) radiation and maintenance TMZ as per consensus of the local multidisciplinary tumor board.\n- 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.\n- If on steroids, stable or decreasing dose for at least 7 days prior to inclusion."}

Exclusion criteria

• {"criterion_text":"- Previous or ongoing participation in other clinical trials with other than standard-of-care tumor-directed treatment(s) for H3K27-altered DMG.\n- Known LVEF < 40 or unstable hemodynamics.\n- Severe hypertension, not adequately controlled with study compatible medication (Adults: RR systolic >180 and/ or RR diastolic >100; Children: >p95 + 12mmHg).\n- History of bleeding disorder and/or coagulopathy.\n- Treatment with anti-coagulant therapy.\n- Severely impaired renal function; creatinine clearance <30 mL/ min.\n- Subjects with significant liver dysfunction; Child Pugh classification C.\n- Known diagnosis of active or untreated hepatitis B, hepatitis C, tuberculosis.\n- Any other illness or medical condition that in the investigator's opinion precludes participation in this study.\n- Pregnant or lactating women.\n- Expected uncontrollable therapy non-compliance/ non-cooperation that is likely to interfere with the study procedure, as per judgement of the investigators.\n- 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.\n- Head circumference ≤ 49 cm.\n- Weight ≥ 135 kg.\n- Patient ≥ 18 years old, who requires general anesthesia to undergo the Exablate BBBO procedure.\n- Contra-indication for MRI procedures.\n- Known sensitivity to gadolinium-based contrast agents.\n- Known sensitivity to the resonator agent (perflutren; Luminity®).\n- 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.\n- Severe dysphagia with feeding tube dependency.\n- Evidence of acute clinically significant intracranial hemorrhage. NB: minimal hemorrhagic foci without obvious related clinical symptoms will not serve as grounds for exclusion.\n- Tumor not visible on any pre-therapy or post-radiation imaging.\n- 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.\n- 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.\n- Patients with right-to-left, bi-directional or transient right-to-left cardiac shunts."}

Primary endpoints

• {"endpoint_text":"- Any serious adverse events (SAE) related to the Exablate BBBO device- and procedure, classified according to the Common Terminology Criteria for Adverse Events (CTCAE) version 6.0.\n- Proportion of patients alive and progression-free at 6 months, based on standardized imaging criteria (e.g., RANO or RAPNO for DMG).","definition_or_measurement_approach":"SAE related to device/procedure will be classified per CTCAE v6.0. Progression-free at 6 months determined by standardized imaging criteria (e.g., RANO or RAPNO for DMG) assessing survival and radiographic progression at 6 months."}

Secondary endpoints

• {"endpoint_text":"- Time from diagnosis to disease progression or death, measured by standardized criteria (e.g., RANO/RAPNO).\n- Time from diagnosis to death from any cause.\n- Radiological response rate according to the response assessment in neuro-oncology criteria (RANO and RAPNO criteria)\n- Extent and consistency of BBB opening as confirmed by T1-weighted contrast-enhanced MRI after each Exablate BBBO session.\n- Incidence of adverse events (AE) over time related to the Exablate BBBO device- and procedure, classified according to the Common Terminology Criteria for Adverse Events (CTCAE) version 6.0.","definition_or_measurement_approach":"Progression and radiological response measured using standardized RANO/RAPNO criteria; overall survival measured as time to death from any cause; BBB opening evaluated by T1-weighted contrast-enhanced MRI after each session; AEs/Incidence classified per CTCAE v6.0."}

Netherlands

Earliest CTIS Part Ii Submission Date

03-02-2026

Latest Decision Or Authorization Date

07-04-2026

Processing Time Days

63

Number Of Sites

2

Number Of Participants

20

Primary sponsor

Full Name

Universitair Medisch Centrum Utrecht

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Third parties

• {"country":"Germany","full_name":"Insightec Europe GmbH","duties_or_roles":"Medical Device expertise; CTIS and Research Portal submission","organisation_type":"Pharmaceutical company"}