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Using focused ultrasound to improve temozolomide treatment for patients with diffuse midline glioma

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What is this study about?

This study is being conducted to evaluate the safety and feasibility of using a specific procedure to help improve the effectiveness of medication for patients with Diffuse Midline Glioma, H3K27-altered. This is a rare type of brain tumor located in the brainstem, which is the part of the brain that connects to the spinal cord. The research focuses on how a method called focused ultrasound-mediated blood-brain barrier opening can assist the delivery of temozolomide, an oral medication used to treat these tumors. The blood-brain barrier is a natural protective layer that prevents many substances from entering the brain, and this procedure aims to temporarily open that barrier to allow the medicine to reach the tumor more effectively.

During the study, participants may undergo the Exablate-BBBO procedure, which uses ultrasound waves to create openings in the protective barrier of the brain. Following this, the medication temozolomide is administered. The study will monitor how well the procedure works and check for any side effects. Effectiveness is also observed through MRI, a medical imaging technique used to create detailed pictures of the inside of the body, to see how the tumor responds to the combined treatment.

Who Can Join the Study?

  • You must be at least 4 years old.
  • You must be able to attend all scheduled study visits, which are the appointments required for the trial.
  • You or your legal guardian must be able and willing to provide informed consent, which is a formal agreement to participate after understanding all study details.
  • A doctor must have confirmed through histology (examining tissue under a microscope) or molecular testing (looking at the genetic makeup of the cells) that you have de novo pontine H3K27-altered diffuse midline glioma. This is a specific type of brain tumor that starts in the brainstem (the part of the brain that controls basic life functions).
  • The main part of the tumor must be located in the brainstem, though some spread to nearby areas like the cerebellar peduncles (structures that connect the brainstem to the cerebellum) is allowed.
  • You must have a functional status score, such as the Karnofsky Performance Score (KPS) or Lansky Performance Score (LPS), of at least 70/70 or 60/60. These scores measure how well a patient can perform daily activities.
  • Your WHO/ECOG performance status, which is a scale used to measure how much a person’s disease affects their daily living abilities, must be 2 or less.
  • You must have an ASA score of I to III. The ASA score is a system used by doctors to measure how healthy a patient is before undergoing medical procedures.
  • You must plan to receive TMZ (a type of chemotherapy medication) and radiation therapy as recommended by your medical team.
  • The first Exabate BBBO procedure must be scheduled within 4 to 6 weeks after finishing radiation or combined radiation and chemotherapy, and no later than 12 weeks after.
  • You must have completed your previous treatments without any grade 3-4 toxicities, which refers to severe or life-threatening side effects. If you did have these side effects, they must have improved to grade 2 (moderate side effects) before joining the study.
  • If you are taking steroids (medicines used to reduce swelling), your dose must have been stable (the same amount) or decreasing for at least 7 days before joining.

Who Cannot Join the Study?

  • Taking part in other clinical trials that use treatments other than the standard care for this specific tumor.
  • Having a low Left Ventricular Ejection Fraction (LVEF), which is a measurement of how much blood the heart pumps out with each beat, or having unstable hemodynamics, which means unstable blood flow and pressure in the body.
  • Having severe hypertension, which is very high blood pressure that is not well-controlled by medicine.
  • A history of bleeding disorders or coagulopathy, which are conditions that prevent blood from clotting properly.
  • Using anti-coagulant therapy, which refers to medications that thin the blood to prevent clots.
  • Having severely impaired renal function, meaning the kidneys are not working well, measured by a creatinine clearance (a test showing how well kidneys filter waste) of less than 30 mL/min.
  • Having significant liver dysfunction, meaning the liver is not working correctly, specifically categorized as Child-Pugh Class C, which is a scale used to measure the severity of liver disease.
  • Having an active or untreated diagnosis of hepatitis B, hepatitis C, or tuberculosis.
  • Any other illness or health problem that the researchers believe makes it unsafe or impossible to join the study.
  • Being pregnant or breastfeeding.
  • Being unable or unwilling to follow the study rules or procedures as decided by the doctors.
  • Having multifocal or leptomeningeal metastasized disease, which means the cancer has spread to multiple spots in the brain or to the protective layers surrounding the brain and spinal cord.
  • Having a head circumference of 49 cm or less.
  • Having a weight of 135 kg or more.
  • Being an adult who requires general anesthesia, which is a state of controlled unconsciousness used during surgery, to undergo the procedure.
  • Having any reason that prevents you from having an MRI (a medical imaging test that uses strong magnets).
  • Having a known allergy or sensitivity to gadolinium-based contrast agents, which are dyes used during imaging to make certain structures clearer.
  • Having a known sensitivity to the resonator agent (a specific substance called perflutren used in the procedure).
  • Showing signs of elevated intracranial pressure (ICP), which means there is too much pressure inside the skull, causing symptoms like headaches, vomiting, vision problems, or changes in consciousness.
  • Having severe dysphagia, which is a serious difficulty in swallowing that requires the use of a feeding tube.
  • Showing evidence of acute intracranial hemorrhage, which is sudden bleeding inside the brain.
  • The tumor cannot be seen on imaging scans before or after radiation treatment.
  • Having metal implants, prostheses, or calcium deposits in or near the head that might interfere with the sound waves used in the treatment.
  • Having another type of cancer that is growing or has been treated in the last 3 years, except for very minor skin cancers.
  • Having a cardiac shunt, which is an abnormal connection or “leak” between the different sides of the heart that allows blood to flow in the wrong direction.

Where you can join this trial?

Verified and Recommended Sites

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Verified Sites

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Other Sites

Site Name City Country Status
Universitair Medisch Centrum Utrecht Utrecht The Netherlands
Prinses Maxima Centrum voor Kinderoncologie B.V. Utrecht The Netherlands

Want to learn more about this study or check if you can participate? Contact us.

Trial status

Country Status Recruitment Start
The Netherlands The Netherlands
Not yet recruiting
01.03.2026

Trial locations

Investigated drugs:

Temozolomide is an oral chemotherapy medication used as a maintenance therapy to help treat certain types of brain tumors.

Exablate-BBBO is a procedure that uses focused ultrasound to temporarily open the blood-brain barrier, which is a protective layer in the brain. This is done to allow medications to reach the tumor more effectively.

Diffuse Midline Glioma, H3K27-altered – This is a type of brain tumor that develops in the central part of the brain, specifically in areas like the pons. These tumors are characterized by a specific genetic change in the H3K27 protein. The disease typically involves the uncontrolled growth of cells within these midline structures. As the tumor grows, it can expand within the brain tissue and affect surrounding nerve pathways. The progression is marked by the continued development of the tumor mass in the central nervous system.

Trial ID:
2025-520814-78-00
Protocol code:
23U-0160
Trial Phase:
Human Pharmacology (Phase I) – Other

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