Focused Ultrasound + Panobinostat for Brain Cancer

No longer recruiting at 2 trial locations

Overseen By Stergios Zacharoulis, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Columbia University

Must be taking: Anticonvulsants

Must not be taking: Anticoagulants

Disqualifiers: Spinal DMGs, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Up to 90 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for brain cancer in children, specifically targeting diffuse midline gliomas (DMG), an aggressive brain tumor. The study tests whether Focused Ultrasound (FUS) with neuro-navigator-controlled sonication can safely open the blood-brain barrier, allowing the drug Panobinostat to reach the tumor more effectively. The goal is to determine if this method can enhance the drug's efficacy and reduce side effects. Children diagnosed with progressive DMG who can swallow capsules might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be on a stable or decreasing dose of steroids and a stable dose of anti-seizure medication for at least one week before joining. It's best to discuss your specific medications with the trial team.

What prior data suggests that this method is safe for opening the blood brain barrier?

Research has shown that using focused ultrasound (FUS) to open the blood-brain barrier (BBB) is generally safe, though some risks exist. Studies have found that FUS can safely and temporarily open the BBB, but there is a risk of brain bleeding or swelling. These side effects, while concerning, are not common.

Panobinostat, the drug used in this study, has been tested in both adults and children with brain tumors. Research indicates it is relatively safe and well-tolerated. Some patients have reported side effects, but many find the drug manageable. It is important to remember that these treatments, while promising, are still under study for safety and effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using Focused Ultrasound (FUS) combined with Panobinostat for treating brain cancer because it introduces a unique approach compared to traditional treatments like surgery, chemotherapy, or radiation. This treatment uses FUS to temporarily open the blood-brain barrier, allowing Panobinostat to penetrate the brain more effectively. Panobinostat is a histone deacetylase inhibitor, which means it can potentially stop cancer cells from growing by altering the way their genes are expressed. This combination could offer a more targeted attack on brain tumors, potentially leading to better outcomes with fewer side effects than conventional therapies.

What evidence suggests that this trial's treatments could be effective for brain cancer?

Research has shown that focused ultrasound (FUS) can temporarily open the blood-brain barrier (BBB), allowing more chemotherapy to reach brain tumors. One study found that FUS increased the drug concentration in specific brain areas, potentially enhancing treatment effectiveness.

In this trial, all participants will receive oral Panobinostat after undergoing FUS. Research indicates that Panobinostat can cross the BBB and reach levels needed to affect tumors like diffuse midline gliomas (DMG), making it a promising option for brain cancer treatment. Panobinostat blocks proteins that help cancer cells grow, which can slow or stop tumor growth.

Using FUS and Panobinostat together in this trial might enhance treatment effectiveness by delivering more of the drug to the tumor and possibly reducing side effects in other parts of the body. Early evidence supports this combination as a promising approach for treating aggressive brain cancers. ^{2 5 6 7 8}

Who Is on the Research Team?

Cheng-Chia Wu, MD, PhD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for children aged 4-21 with progressive diffuse midline glioma (DMG) who've recovered from prior cancer treatments. They must be able to undergo MRI scans, swallow capsules, and have a stable health condition as assessed by the investigator. Those with spinal DMGs, bleeding disorders, metal implants, or severe systemic diseases are excluded.

Inclusion Criteria

I am between 4 and 21 years old.

My tumor in the brain stem or thalamus is confirmed by imaging or has a specific genetic change.

My brain tumor is growing or spreading.

Exclusion Criteria

Pregnant or breast-feeding women

I am allergic to Panobinostat or similar drugs, or to gadolinium.

I have a bleeding disorder that cannot be corrected.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Focused Ultrasound (FUS) treatment with microbubbles and neuro-navigator-controlled sonication, followed by oral Panobinostat administration

Up to 90 days

Periodic MRIs to confirm BBB opening and closing

Follow-up

Participants are monitored for safety and effectiveness after treatment, including overall survival and progression-free survival

Up to 6 months

Follow-up every 3-6 months

What Are the Treatments Tested in This Trial?

Interventions

• Focused Ultrasound with neuro-navigator-controlled sonication
• Panobinostat

Trial Overview The study tests if Focused Ultrasound (FUS) can safely open the blood-brain barrier in kids with DMG to enhance Panobinostat delivery to brain tumors. The non-invasive FUS will target up to three areas near the tumor while administering oral Panobinostat.

How Is the Trial Designed?

Group I: FUS using Oral Panobinostat Experimental Treatment 2 Interventions

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 is already approved in United States, European Union for the following indications:

Approved in United States as Farydak for:

• Multiple myeloma

Approved in European Union as Farydak for:

• Multiple myeloma

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Cheng-Chia (Fred) Wu

Lead Sponsor

Trials

2

Recruited

10+

Focused Ultrasound Foundation

Collaborator

Trials

18

Recruited

460+

Published Research Related to This Trial

Diffuse Midline Glioma (DMG), previously known as Diffuse Intrinsic Pontine Glioma (DIPG), is a challenging pediatric brain tumor with no curative treatments available despite over 250 clinical trials.

Focused Ultrasound (FUS) is a promising noninvasive technology that can temporarily disrupt the blood-brain barrier, potentially allowing for better delivery of therapies and enhancing the effectiveness of treatments like chemotherapy and radiation for DMG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Past, present and future of Focused Ultrasound as an adjunct or complement to DIPG/DMG therapy: A consensus of the 2021 FUSF DIPG meeting. Parekh, K., LeBlang, S., Nazarian, J., et al.[2023]

Using focused ultrasound (FUS) to enhance the delivery of liposomal doxorubicin significantly reduced tumor growth in rats with brain tumors compared to doxorubicin treatment alone, indicating improved drug delivery across the blood-brain barrier.

The combination of FUS and doxorubicin treatment resulted in a modest but significant increase in median survival time for the rats, suggesting that this method could enhance the effectiveness of chemotherapy for brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved anti-tumor effect of liposomal doxorubicin after targeted blood-brain barrier disruption by MRI-guided focused ultrasound in rat glioma. Treat, LH., McDannold, N., Zhang, Y., et al.[2022]

In a study involving 13 adult patients with advanced solid tumors or cutaneous T-cell lymphoma, panobinostat was well tolerated at doses up to 20 mg, with no dose-limiting toxicity observed in 12 evaluable patients.

The most common side effects were diarrhea and nausea, experienced by 76.9% of patients, while thrombocytopenia occurred in 92.3%, indicating a need for monitoring blood cell levels during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of oral panobinostat (LBH589) in Japanese patients with advanced solid tumors. Fukutomi, A., Hatake, K., Matsui, K., et al.[2022]

Panobinostat, a histone deacetylase inhibitor for treating relapsed multiple myeloma, primarily undergoes metabolism through the CYP3A4 enzyme, which is crucial for understanding its drug interactions and dosing.

Physiologically based pharmacokinetic (PBPK) modeling predicted that the presence of rifampin, a strong CYP3A4 inducer, could significantly reduce panobinostat exposure by 65%, while its absorption is not affected by changes in stomach pH, leading to important dosing recommendations for clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physiologically Based Pharmacokinetic Model Predictions of Panobinostat (LBH589) as a Victim and Perpetrator of Drug-Drug Interactions. Einolf, HJ., Lin, W., Won, CS., et al.[2018]

Using focused ultrasound (FUS) combined with microbubbles (MBs) significantly enhances the delivery of the chemotherapy drug panobinostat to diffuse intrinsic pontine glioma (DIPG) tumors in mice, resulting in a threefold increase in drug concentration at the tumor site.

The combination treatment led to a 71% reduction in tumor volume and improved survival from 21 to 31 days, demonstrating a promising therapeutic effect against this challenging pediatric brain tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRI-Guided Focused Ultrasound Blood-Brain Barrier Opening Increases Drug Delivery and Efficacy in a Diffuse Midline Glioma Mouse Model. Martinez, P., Nault, G., Steiner, J., et al.[2023]

Panobinostat (Farydak(®)) is an HDAC inhibitor that has been approved in the US for use in combination with bortezomib and dexamethasone to treat recurrent multiple myeloma in patients who have undergone at least two prior treatments.

The drug is currently being explored in clinical trials for various hematological and solid tumors, indicating its potential as a versatile cancer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panobinostat: first global approval. Garnock-Jones, KP.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9563027/

Applications of Focused Ultrasound for the Treatment of ... Unlike imaging forms of ultrasound, FUS can successfully penetrate the skull surrounding the brain, allowing for non-invasive ablation of tumor ...

2. fusfoundation.org fusfoundation.org/diseases-and-conditions/glioblastoma/

Glioblastoma Focused ultrasound enables enhanced chemotherapy dose for the target, with less impact to the rest of the patient. It can be repeated, if ...

3. umms.org umms.org/umgccc/news/2025/researchers-detail-reliable-measurement-for-blood-brain-barrier-opening

University of Maryland School of Medicine Researchers ... The data in this study were collected from a subset of glioblastoma patients enrolled in a clinical trial led by Dr. Woodworth where focused ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT07179328

NCT07179328 | Focused Ultrasound Blood-Brain Barrier ... The goal of this clinical trial is to evaluate the safety and feasibility of focused ultrasound (FUS)-mediated blood-brain barrier (BBB) ...

5. thejns.org thejns.org/view/journals/j-neurosurg/142/6/article-p1635.xml

Focused ultrasound therapy as a strategy for improving ... The study demonstrated successful BBB disruption in all 5 patients, with greater drug concentrations in brain regions with BBB disruption ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7327352/

Neuronavigation-guided focused ultrasound (NaviFUS) for ... The objectives of this study were to investigate the safety, feasibility and the tolerated dose of transient opening of the BBB by using the NaviFUS System in ...

7. nature.com nature.com/articles/s41698-023-00448-y

First-in-human prospective trial of sonobiopsy in high- ... These feasibility and safety data support the continued investigation of sonobiopsy for noninvasive molecular diagnosis of brain diseases.

8. fusfoundation.org fusfoundation.org/posts/recurrent-glioblastoma-clinical-trial-results-of-sonocloud-9-plus-chemotherapy/

Recurrent Glioblastoma Clinical Trial Results of ... The safety and efficacy of the treatment were the primary outcome measures (Phase 1 evaluated the safety of escalating the number of ultrasound ...