Diffuse Midline Glioma, H3 K27-AlteredPhase 1/2FIDESNCT07562971
Focused Ultrasound Blood-Brain Barrier Opening in Pontine Diffuse Midline Glioma to Enhance Temozolomide Therapy: Pilot Feasibility Study (FIDES)
A Phase 1/2 study testing Focused Ultrasound (FUS) Blood-Brain Barrier Opening and Temozolomide (TMZ) in people with Diffuse Midline Glioma, H3 K27-Altered, run by UMC Utrecht at 2 sites in Netherlands.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 4 years and older
- Conditions the study is for
- Diffuse Midline Glioma, H3 K27-Altered
- What is being tested?
- Focused Ultrasound (FUS) Blood-Brain Barrier Opening and Temozolomide (TMZ)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesNetherlands
- Study dates
- May 2026to Nov 2031
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
- ASA-score of I-III.
- Intention to treat with (TMZ chemo-) radiation and maintenance TMZ as per consensus of the local multidisciplinary tumor board.
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- 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.
- 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.
Who cannot join
- 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.
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- 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 study compatible 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 other 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®).
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands2 sites
Princess Maxima Center for pediatric oncology
Utrecht, 3584 CS
Dannis G. van Vuurden, MD, PhD, +31 88 972 9736, secretariaatneuro-onco@prinsesmaximacentrum.nl
fides@umcutrecht.nl
UMC Utrecht
Utrecht, 3584 CX
Tom J. Snijders, MD, PhD, +31 88 75 679 95, fides@umcutrecht.nl
fides@umcutrecht.nl
About this study
Official title: Focused Ultrasound-mediated Blood-Brain Barrier Opening In Pontine Diffuse Midline Glioma (DMG) to Enhance Systemic Therapy With Temozolomide (FIDES) - an Exploratory Pilot and Feasibility Trial
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.
Read more
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.
- Conditions
- Diffuse Midline Glioma, H3 K27-Altered
- Being tested
- Focused Ultrasound (FUS) Blood-Brain Barrier Opening, Temozolomide (TMZ)
- Keywords
- DMG, DIPG, Focused ultrasound, Exablate, Temozolomide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Focused Ultrasound (FUS) Blood-Brain Barrier OpeningDevice
Also called Exablate BBBO, Exablate Neuro
FUS-BBB opening involves the application of acoustic energy at low frequencies from over 1000 individual transducers to induce localized and temporary blood-brain barrier disruption in patients. FUS-BBBO will be applied during each temozolomide cycle.
Temozolomide (TMZ)Drug
Patients will undergo six standard-of-care cycles of temozolomide maintenance therapy. Each cycle will be combined with FUS-BBBO.
| Study group | Role | What they receive |
|---|---|---|
| FUS-BBBO-mediated delivery of temozolomide | Experimental | The Exablate Model 4000 Type 2 system is used to induce localized and temporary blood-brain barrier opening in adult and pediatric patients with H3K27-altered pontine DMG undergoing standard of care temozolomide chemotherapy. Receives: Device: Focused Ultrasound (FUS) Blood-Brain Barrier Opening; Drug: Temozolomide (TMZ) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Device and procedure related adverse events
The number and severity of device and Exablate BBBO procedure related adverse events (CTCAE version 6.0), will be assessed based on radiographical and clinical parameters.
Measured: Up to 72 hours after each Exablate BBBO procedure
6-month progression-free survival (PFS6)
Proportion of patients alive and progression-free at 6 months, based on standardized imaging criteria (e.g., RANO or RAPNO for DMG).
Measured: From date of diagnosis until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2026
- Study startMay 2026 (estimated)
- Primary completionNov 2030 (estimated)
- Study completionNov 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Midline Glioma, H3 K27-AlteredStudies of the same condition, open and under way.
- More trials run by UMC UtrechtThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- Collaborators
- Princess Maxima Center for Pediatric Oncology
- Responsible party
- Principal investigator, Tom J. Snijders, MD PhD, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07562971
- Sponsor's protocol ID
- UMC_Utrecht
- Other IDs
- 2025-520814-78-00, NL-009201, 2025
- Acronym
- FIDES
- Status last verified
- Apr 2026
- First submitted
- 21 Apr 2026
- Last updated
- 1 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Metadata of FIDES will be published on a repository. Researchers may request IPD, the study team will decide if the request can be granted.
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Focused Ultrasound-mediated Blood-Brain Barrier Opening In Pontine Diffuse Midline Glioma (DMG) to Enhance Systemic Therapy With Temozolomide (FIDES) - an Exploratory Pilot and Feasibility Trial
- ClinicalTrials.gov ID
- NCT07562971
- Acronym / sponsor ID
- FIDES / UMC_Utrecht
- Conditions
- Diffuse Midline Glioma, H3 K27-Altered
- Keywords
- DMG, DIPG, Focused ultrasound, Exablate, Temozolomide
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- Collaborators
- Princess Maxima Center for Pediatric Oncology
- Study start
- May 2026 (estimated)
- Primary completion
- Nov 2030 (estimated)
- Study completion
- Nov 2031 (estimated)
- First posted
- 1 May 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| FUS-BBBO-mediated delivery of temozolomide | Experimental | Device: Focused Ultrasound (FUS) Blood-Brain Barrier Opening, Drug: Temozolomide (TMZ)The Exablate Model 4000 Type 2 system is used to induce localized and temporary blood-brain barrier opening in adult and pediatric patients with H3K27-altered pontine DMG undergoing standard of care temozolomide chemotherapy. |
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
- ASA-score of I-III.
Key exclusion criteria (25 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Focused Ultrasound (FUS) Blood-Brain Barrier OpeningAlso: Exablate BBBO, Exablate NeuroFUS-BBB opening involves the application of acoustic energy at low frequencies from over 1000 individual transducers to induce localized and temporary blood-brain barrier disruption in patients. FUS-BBBO will be applied during each temozolomide cycle. | Device | FUS-BBBO-mediated delivery of temozolomide |
| Temozolomide (TMZ)Patients will undergo six standard-of-care cycles of temozolomide maintenance therapy. Each cycle will be combined with FUS-BBBO. | Drug | FUS-BBBO-mediated delivery of temozolomide |
Primary outcome
Device and procedure related adverse events
Time frame: Up to 72 hours after each Exablate BBBO procedure
The number and severity of device and Exablate BBBO procedure related adverse events (CTCAE version 6.0), will be assessed based on radiographical and clinical parameters.
6-month progression-free survival (PFS6)
Time frame: From date of diagnosis until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months.
Proportion of patients alive and progression-free at 6 months, based on standardized imaging criteria (e.g., RANO or RAPNO for DMG).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2026.
- Individual participant dataSharing planned: Yes. Metadata of FIDES will be published on a repository. Researchers may request IPD, the study team will decide if the request can be granted.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Princess Maxima Center for pediatric oncology
Utrecht, Netherlands
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Focused Ultrasound (FUS) Blood-Brain Barrier Opening and Temozolomide (TMZ) in people with Diffuse Midline Glioma, H3 K27-Altered, run by UMC Utrecht at 2 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 1 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Device and procedure related adverse events (time frame: Up to 72 hours after each Exablate BBBO procedure). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2026; AzTrials last refreshed its copy on 7 Nov 2026.