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

NCT04804709 | Terminated Phase 1 Results DMC FDA Drug FDA Device

• 1 other identifier: AAAS5953
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The blood brain barrier (BBB) prevents some drugs from successfully reaching the target tumor. Focused Ultrasound (FUS) using microbubbles and neuro-navigator-controlled sonication is a non-invasive method of temporarily opening up the blood brain barrier to allow a greater concentration of the drug to reach into the brain tumor. This may improve response and may also reduce system side effects in the patient. The primary purpose of this study is to evaluate the feasibility of safely opening the BBB in children with progressive diffuse midline gliomas (DMG) treated with oral Panobinostat using FUS with microbubbles and neuro-navigator-controlled sonication. For the purpose of the study, the investigators will be opening up the BBB temporarily in one, two, or three locations around the tumor using the non-invasive FUS technology, and administrating oral Panobinostat in children with progressive DMG.

Conditions

Diffuse Intrinsic Pontine Glioma; Diffuse Pontine and Thalamic Gliomas; Diffuse Midline Glioma, H3 K27M-Mutant

Keywords

Blood brain barrier; Diffuse Midline Gliomas; Focused Ultrasound; Pontine Gliomas; Thalamic Gliomas

Outcome Measures

Primary Outcomes (1)

• Number of Adverse Events

  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).

  Up to 7 months

Secondary Outcomes (3)

• Progression Free Survival at 6 Months (PFS6)

  Up to 6 months

• Overall Survival at 6 Months (OS6)

  Up to 7 months

• Number of Subjects With Blood Brain Barrier/Tumor Imaging Changes

  Up to 8 months

Study Arms (1)

FUS using Oral Panobinostat

EXPERIMENTAL

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.

Drug: Panobinostat 15 MG; Device: Focused Ultrasound with neuro-navigator-controlled sonication

Interventions

Panobinostat 15 MG DRUG

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).

Also known as: FARYDAK

FUS using Oral Panobinostat

Focused Ultrasound with neuro-navigator-controlled sonication DEVICE

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.

FUS using Oral Panobinostat

Eligibility Criteria

• Age: 4 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Ages 4-21 years.
• Subjects with evidence of clinical and/or radiographic progression of Diffuse Midline Glioma
• Radiological diagnosis of DMG with tumor involving the pons (intrinsic, pontine based infiltrative lesion; hypointense in T1 weighted images (T1WIs) and hyperintense in T2 sequences, with mass effect on the adjacent structures and occupying at least 50% of the pons), thalami and/or histological confirmation of H3K27M mutation confirmation of pontine or thalamic glioma.
• Subjects must be healthy enough to tolerate FUS and MRI and any anesthesia necessary based on the opinion of the principal investigator. Subjects must also be able to swallow capsules (for Panobinostat dosing). Other criteria include, but is not limited to:
• Prior therapy:
• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment.
• Cytotoxic chemotherapy or anti-cancer agents known to be myelosuppressive: At least 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy.
• Anti-cancer agents not known to be myelosuppressive: At least 7 days must have elapsed from last dose of agent.
• Antibodies: At least 21 days must have elapsed from infusion of last dose of antibody.
• Interleukins, Interferons, and Cytokines: At least 21 days must have elapsed since the completion of interleukins, interferon, or cytokines.
• Stem cell infusions: At least 42 days must have elapsed after completion of an autologous stem cell infusion, and at least 84 days must have elapsed after completion of an allogeneic stem cell infusion.
• Cellular therapy: At least 42 days must have elapsed since the completion of any type of cellular therapy
• Radiotherapy (XRT): At least 1 month must have elapsed after local XRT.
• Subjects must be on a stable or decreasing dose of steroids, as well as stable dose of anti-seizure medication for 1 week.
• Performance status:

You may not qualify if:

• Subjects with spinal DMGs.
• Subjects with a medical condition that would preclude general anesthesia
• Subjects with evidence of any active infection
• Subjects with documented allergy to compounds of similar chemical or biologic composition to Panobinostat or gadolinium compounds
• Subjects with evidence of tumor hemorrhage
• Subjects with an uncorrectable bleeding disorder
• Subjects with signs of impending herniation or an acute intratumoral hemorrhage
• Subjects with systemic diseases which may be associated with unacceptable anesthetic/operative risk
• Subjects with implanted electrical devices, metallic implants
• Subjects with uncontrollable hypertension
• Subjects with a history of stroke or cardiovascular disease
• Subjects with cerebrovascular diseases
• Subjects with coagulopathy or under anticoagulant therapy.
• Pregnant or breast-feeding women will not be entered on this study, since there is yet no available information regarding human fetal or teratogenic toxicities. A pregnancy test must be obtained in girls who are post-menarchal. Males with female partners of reproductive potential or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control- including a medically accepted barrier method of contraception (e.g., a male or female condom) for the entire period in which they are receiving protocol therapy and for at least 1 week following their last study treatment requirement. Abstinence is an acceptable method of birth control.

Sponsors & Collaborators

• Columbia University: lead
• Focused Ultrasound Foundation: collaborator

Study Sites (1)

Columbia University Irving Medical Center / NewYork-Presbyterian Hospital

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Diffuse Intrinsic Pontine Glioma

Interventions

Panobinostat

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Trial could not be continued due to the manufacturer of Panobinostat discontinuing the drug during the course of the trial.

Results Point of Contact

• Title: Cheng-Chia Wu, MD, PhD
• Organization: Columbia University Irving Medical Center

cw2666@cumc.columbia.edu

646-317-3033

Study Officials

• Cheng-Chia Wu, MD, PhD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2021
• First Posted: March 18, 2021
• Study Start: July 28, 2021
• Primary Completion: March 1, 2022
• Study Completion: March 31, 2022
• Last Updated: June 8, 2025
• Results First Posted: June 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)