This study is for people (children and adults) with a rare and aggressive brain tumor called H3K27-altered diffuse midline glioma (DMG) located in the pons, a deep part of the brainstem. These tumors are very difficult to treat because they grow into surrounding brain tissue and cannot be fully removed with surgery. Most patients currently survive less than one year after diagnosis, and treatment options are limited.
Current standard treatment The usual treatment is radiotherapy, sometimes combined with a chemotherapy drug called temozolomide (TMZ). This combination may slightly improve outcomes, but it is often not very effective for tumors in the pons. One possible reason is that the blood-brain barrier (BBB)-a natural protective filter in the brain-may be especially strong in this area, making it harder for medicines to reach the tumor.
What this study is testing This study is exploring a new approach to help chemotherapy reach the tumor more effectively. It uses MRI-guided focused ultrasound (with the Exablate system) to temporarily and safely open the blood-brain barrier in the tumor area. This may allow more temozolomide to enter the tumor.
Study goal
The main goal is to find out:
* Whether this technique is safe * Whether it may help slow tumor growth or extend survival
Who can join
* Adults and children aged 4 years and older * Diagnosed with H3K27-altered pontine DMG * Eligible for temozolomide after completing radiation therapy
The study will include 20 participants (about half children and half adults).
What participants will do
Participants will:
* Receive 6 cycles of temozolomide chemotherapy * Undergo focused ultrasound blood-brain barrier opening on the first day of each cycle * Have regular MRI scans and check-ups to monitor safety and tumor response
Each treatment cycle includes 5 days of chemotherapy followed by a rest period of 23 days.
What the study is measuring
Researchers will look at:
* Safety of the procedure and device * How long patients live without tumor progression (progression-free survival) * Overall survival * Tumor response to treatment * Whether the procedure is practical to use in clinical care
They will also compare results to data from previous patients in international brain tumor registries.
Why this study matters This study is testing whether temporarily opening the brain's natural barrier can help chemotherapy work better in a type of brain tumor that currently has very limited treatment options.
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 and WHO/ECOG performance status ≤ 2.
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.
UMC Utrecht
Lead sponsor
Princess Maxima Center for Pediatric Oncology
Collaborator