Trial Outcomes & Findings for Non-Invasive Focused Ultrasound (FUS) With Oral Panobinostat in Children With Progressive Diffuse Midline Glioma (DMG) (NCT NCT04804709)

Last Updated: 2025-06-08

Results Overview

Safety will be assessed by evaluation of physical and neurologic examinations, laboratory studies, radiographic studies, and by adverse events as per the CTCAE version 5.0. An adverse event is any new or worsening symptom or clinical finding which occurs during the study period. Adverse events are to be recorded irrespective of causality on the adverse event form. Each event will be described by its severity (mild, moderate, severe, life-threatening), duration, and relation to the study medication (unrelated, unlikely, possible, probable, and definite).

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

5 participants

Primary outcome timeframe

Up to 7 months

Results posted on

2025-06-08

Participant Flow

5 participants in total consented, but only 3 participants went on to take part in the study. The study was halted prematurely due to the withdrawal of Panobinostat from the US Market and did not meet the target enrollment of 15.

Participant milestones

Participant milestones
Measure	FUS Using Oral Panobinostat All patients enrolled in the study will be treated with oral Panobinostat after receiving Focused Ultrasound treatment (FUS) with microbubbles and neuro-navigator-controlled sonication. Panobinostat 15 MG: After each instance of opening the BBB using specific parameters of focused ultrasound in the specific number of tumor sites (one, two, or three), the subjects will receive oral Panobinostat (15 mg/m\^2). Focused Ultrasound with neuro-navigator-controlled sonication: The purpose of this study is to evaluate the feasibility of opening the BBB safely using specific parameters of focused ultrasound in progressive/recurrent diffuse midline gliomas in one, two, or three tumor sites. The trial will follow a 3+3 Number of Tumor Sites (NOTS) escalation scheme. The "number of tumor sites" in reference to here is the number of openings in the blood-brain barrier using Focused Ultrasound (FUS). Subjects will start the first cycle of the treatment arm with 1 tumor site and move on to incrementing NOTS levels if no dose-limiting toxicities (DLTs) are observed.
Overall Study STARTED	3
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Non-Invasive Focused Ultrasound (FUS) With Oral Panobinostat in Children With Progressive Diffuse Midline Glioma (DMG)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FUS Using Oral Panobinostat n=3 Participants All patients enrolled in the study will be treated with oral Panobinostat after receiving Focused Ultrasound treatment (FUS) with microbubbles and neuro-navigator-controlled sonication. Panobinostat 15 MG: After each instance of opening the BBB using specific parameters of focused ultrasound in the specific number of tumor sites (one, two, or three), the subjects will receive oral Panobinostat (15 mg/m\^2). Focused Ultrasound with neuro-navigator-controlled sonication: The purpose of this study is to evaluate the feasibility of opening the BBB safely using specific parameters of focused ultrasound in progressive/recurrent diffuse midline gliomas in one, two, or three tumor sites. The trial will follow a 3+3 Number of Tumor Sites (NOTS) escalation scheme. The "number of tumor sites" in reference to here is the number of openings in the blood-brain barrier using Focused Ultrasound (FUS). Subjects will start the first cycle of the treatment arm with 1 tumor site and move on to incrementing NOTS levels if no dose-limiting toxicities (DLTs) are observed.
Age, Categorical <=18 years	2 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 7 months

Outcome measures

Outcome measures
Measure	FUS Using Oral Panobinostat n=3 Participants All patients enrolled in the study will be treated with oral Panobinostat after receiving Focused Ultrasound treatment (FUS) with microbubbles and neuro-navigator-controlled sonication. Panobinostat 15 MG: After each instance of opening the BBB using specific parameters of focused ultrasound in the specific number of tumor sites (one, two, or three), the subjects will receive oral Panobinostat (15 mg/m\^2). Focused Ultrasound with neuro-navigator-controlled sonication: The purpose of this study is to evaluate the feasibility of opening the BBB safely using specific parameters of focused ultrasound in progressive/recurrent diffuse midline gliomas in one, two, or three tumor sites. The trial will follow a 3+3 Number of Tumor Sites (NOTS) escalation scheme. The "number of tumor sites" in reference to here is the number of openings in the blood-brain barrier using Focused Ultrasound (FUS). Subjects will start the first cycle of the treatment arm with 1 tumor site and move on to incrementing NOTS levels if no dose-limiting toxicities (DLTs) are observed.
Number of Adverse Events	31 adverse events

SECONDARY outcome

Timeframe: Up to 6 months

PFS is defined as the duration of the time from the start of FUS treatment to time of progression or death from any cause, whichever occurs first. Response and progression will be evaluated in this study using the international criteria proposed by the updated Pediatric Response Assessment in Neuro-oncology (RANO) guidelines.

Outcome measures

Outcome measures
Measure	FUS Using Oral Panobinostat n=3 Participants All patients enrolled in the study will be treated with oral Panobinostat after receiving Focused Ultrasound treatment (FUS) with microbubbles and neuro-navigator-controlled sonication. Panobinostat 15 MG: After each instance of opening the BBB using specific parameters of focused ultrasound in the specific number of tumor sites (one, two, or three), the subjects will receive oral Panobinostat (15 mg/m\^2). Focused Ultrasound with neuro-navigator-controlled sonication: The purpose of this study is to evaluate the feasibility of opening the BBB safely using specific parameters of focused ultrasound in progressive/recurrent diffuse midline gliomas in one, two, or three tumor sites. The trial will follow a 3+3 Number of Tumor Sites (NOTS) escalation scheme. The "number of tumor sites" in reference to here is the number of openings in the blood-brain barrier using Focused Ultrasound (FUS). Subjects will start the first cycle of the treatment arm with 1 tumor site and move on to incrementing NOTS levels if no dose-limiting toxicities (DLTs) are observed.
Progression Free Survival at 6 Months (PFS6)	70 days Interval 16.0 to 142.0

SECONDARY outcome

Timeframe: Up to 7 months

Overall survival is defined as the duration of time from the start of FUS treatment to death from any cause. OS will be measured by follow-up with a study participant every 3-6 months until death for any reason.

Outcome measures

Outcome measures
Measure	FUS Using Oral Panobinostat n=3 Participants All patients enrolled in the study will be treated with oral Panobinostat after receiving Focused Ultrasound treatment (FUS) with microbubbles and neuro-navigator-controlled sonication. Panobinostat 15 MG: After each instance of opening the BBB using specific parameters of focused ultrasound in the specific number of tumor sites (one, two, or three), the subjects will receive oral Panobinostat (15 mg/m\^2). Focused Ultrasound with neuro-navigator-controlled sonication: The purpose of this study is to evaluate the feasibility of opening the BBB safely using specific parameters of focused ultrasound in progressive/recurrent diffuse midline gliomas in one, two, or three tumor sites. The trial will follow a 3+3 Number of Tumor Sites (NOTS) escalation scheme. The "number of tumor sites" in reference to here is the number of openings in the blood-brain barrier using Focused Ultrasound (FUS). Subjects will start the first cycle of the treatment arm with 1 tumor site and move on to incrementing NOTS levels if no dose-limiting toxicities (DLTs) are observed.
Overall Survival at 6 Months (OS6)	91 days Interval 70.0 to 192.0

SECONDARY outcome

Timeframe: Up to 8 months

MRI and other radiological evidence to show successful blood brain barrier (BBB) opening and closing will be reviewed and tallied.

Outcome measures

Outcome measures
Measure	FUS Using Oral Panobinostat n=3 Participants All patients enrolled in the study will be treated with oral Panobinostat after receiving Focused Ultrasound treatment (FUS) with microbubbles and neuro-navigator-controlled sonication. Panobinostat 15 MG: After each instance of opening the BBB using specific parameters of focused ultrasound in the specific number of tumor sites (one, two, or three), the subjects will receive oral Panobinostat (15 mg/m\^2). Focused Ultrasound with neuro-navigator-controlled sonication: The purpose of this study is to evaluate the feasibility of opening the BBB safely using specific parameters of focused ultrasound in progressive/recurrent diffuse midline gliomas in one, two, or three tumor sites. The trial will follow a 3+3 Number of Tumor Sites (NOTS) escalation scheme. The "number of tumor sites" in reference to here is the number of openings in the blood-brain barrier using Focused Ultrasound (FUS). Subjects will start the first cycle of the treatment arm with 1 tumor site and move on to incrementing NOTS levels if no dose-limiting toxicities (DLTs) are observed.
Number of Subjects With Blood Brain Barrier/Tumor Imaging Changes	3 Participants

Adverse Events

FUS Using Oral Panobinostat

Serious events: 1 serious events

Other events: 3 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	FUS Using Oral Panobinostat n=3 participants at risk All patients enrolled in the study will be treated with oral Panobinostat after receiving Focused Ultrasound treatment (FUS) with microbubbles and neuro-navigator-controlled sonication. Panobinostat 15 MG: After each instance of opening the BBB using specific parameters of focused ultrasound in the specific number of tumor sites (one, two, or three), the subjects will receive oral Panobinostat (15 mg/m\^2). Focused Ultrasound with neuro-navigator-controlled sonication: The purpose of this study is to evaluate the feasibility of opening the BBB safely using specific parameters of focused ultrasound in progressive/recurrent diffuse midline gliomas in one, two, or three tumor sites. The trial will follow a 3+3 Number of Tumor Sites (NOTS) escalation scheme. The "number of tumor sites" in reference to here is the number of openings in the blood-brain barrier using Focused Ultrasound (FUS). Subjects will start the first cycle of the treatment arm with 1 tumor site and move on to incrementing NOTS levels if no dose-limiting toxicities (DLTs) are observed.
Cardiac disorders Grade 5 Cardiac Arrest	33.3% 1/3 • Number of events 1 • Up to 7 months

Other adverse events

Other adverse events
Measure	FUS Using Oral Panobinostat n=3 participants at risk All patients enrolled in the study will be treated with oral Panobinostat after receiving Focused Ultrasound treatment (FUS) with microbubbles and neuro-navigator-controlled sonication. Panobinostat 15 MG: After each instance of opening the BBB using specific parameters of focused ultrasound in the specific number of tumor sites (one, two, or three), the subjects will receive oral Panobinostat (15 mg/m\^2). Focused Ultrasound with neuro-navigator-controlled sonication: The purpose of this study is to evaluate the feasibility of opening the BBB safely using specific parameters of focused ultrasound in progressive/recurrent diffuse midline gliomas in one, two, or three tumor sites. The trial will follow a 3+3 Number of Tumor Sites (NOTS) escalation scheme. The "number of tumor sites" in reference to here is the number of openings in the blood-brain barrier using Focused Ultrasound (FUS). Subjects will start the first cycle of the treatment arm with 1 tumor site and move on to incrementing NOTS levels if no dose-limiting toxicities (DLTs) are observed.
Blood and lymphatic system disorders Anemia	66.7% 2/3 • Number of events 11 • Up to 7 months
Blood and lymphatic system disorders Platelet count decreased	100.0% 3/3 • Number of events 10 • Up to 7 months
Blood and lymphatic system disorders Hypokalemia	66.7% 2/3 • Number of events 10 • Up to 7 months
Blood and lymphatic system disorders Lymphocyte count decreased	66.7% 2/3 • Number of events 20 • Up to 7 months
Blood and lymphatic system disorders Hypophosphatemia	33.3% 1/3 • Number of events 6 • Up to 7 months
Blood and lymphatic system disorders Hyperglycemia	100.0% 3/3 • Number of events 14 • Up to 7 months
Blood and lymphatic system disorders hypermagnesemia	66.7% 2/3 • Number of events 5 • Up to 7 months
Blood and lymphatic system disorders Hypomagnesemia	33.3% 1/3 • Number of events 1 • Up to 7 months
Blood and lymphatic system disorders Hyperphosphatemia	33.3% 1/3 • Number of events 1 • Up to 7 months
Blood and lymphatic system disorders alanine aminotransferase increased	66.7% 2/3 • Number of events 8 • Up to 7 months
Blood and lymphatic system disorders Aspartate aminotransferase increased	66.7% 2/3 • Number of events 10 • Up to 7 months
Blood and lymphatic system disorders hypocalcemia	100.0% 3/3 • Number of events 10 • Up to 7 months
Blood and lymphatic system disorders Hypoalbuminemia	100.0% 3/3 • Number of events 5 • Up to 7 months
Infections and infestations Urinary tract infection	33.3% 1/3 • Number of events 2 • Up to 7 months
Gastrointestinal disorders Nausea	100.0% 3/3 • Number of events 6 • Up to 7 months
Gastrointestinal disorders Vomiting	66.7% 2/3 • Number of events 4 • Up to 7 months
Vascular disorders Flushing	66.7% 2/3 • Number of events 2 • Up to 7 months
Infections and infestations Otitis media	33.3% 1/3 • Number of events 1 • Up to 7 months
Nervous system disorders Headache	33.3% 1/3 • Number of events 1 • Up to 7 months
Cardiac disorders Bradycardia	33.3% 1/3 • Number of events 1 • Up to 7 months
Gastrointestinal disorders Dyspepsia	33.3% 1/3 • Number of events 1 • Up to 7 months
Investigations Blood bicarbonate decreased	33.3% 1/3 • Number of events 1 • Up to 7 months
Gastrointestinal disorders Dry mouth	33.3% 1/3 • Number of events 1 • Up to 7 months
Eye disorders Dry eye	33.3% 1/3 • Number of events 1 • Up to 7 months
Skin and subcutaneous tissue disorders Excoriation	33.3% 1/3 • Number of events 1 • Up to 7 months
Respiratory, thoracic and mediastinal disorders Hypoxia	33.3% 1/3 • Number of events 2 • Up to 7 months
Gastrointestinal disorders Diarrhea	33.3% 1/3 • Number of events 2 • Up to 7 months
Infections and infestations COVID-19	33.3% 1/3 • Number of events 1 • Up to 7 months
Blood and lymphatic system disorders Hyponatremia	66.7% 2/3 • Number of events 2 • Up to 7 months
Blood and lymphatic system disorders Blood LDH increased	33.3% 1/3 • Number of events 1 • Up to 7 months

Additional Information

Cheng-Chia Wu, MD, PhD

Columbia University Irving Medical Center

Phone: 646-317-3033

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place