What side effects are associated with this type of intervention?

Treatments for Diffuse Intrinsic Pontine Glioma (DIPG) that involve opening the blood-brain barrier (BBB) to enhance drug delivery, such as Focused Ultrasound (FUS) with microbubbles and neuro-navigator-controlled sonication, may present side effects including neurotoxicity, cerebral edema, and potential damage to surrounding brain tissue. The specific drugs used in these treatments, like Panobinostat, can also cause side effects such as fatigue, diarrhea, and hematologic abnormalities. These approaches aim to improve drug concentration in the tumor while potentially reducing systemic side effects.

What other types of research exist?

Promising novel alternatives for DIPG treatment in 2024 include: 1) Convection-enhanced delivery (CED) of therapeutic agents, which allows for direct infusion of drugs into the tumor site, bypassing the blood-brain barrier. 2) Immunotherapy approaches, such as CAR T-cell therapy, which harness the patient's immune system to target and destroy cancer cells. 3) Targeted molecular therapies, including inhibitors of specific genetic mutations or pathways involved in DIPG, such as ONC201, which targets the DRD2 receptor. 4) Novel radiotherapy techniques, such as proton beam therapy, which can deliver high doses of radiation with precision to minimize damage to surrounding healthy tissue.

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Histone Deacetylase Inhibitor

Focused Ultrasound + Panobinostat for Brain Cancer

Q: What prior FDA approvals exist?

As of now, there are no FDA-approved treatments specifically for Diffuse Intrinsic Pontine Glioma (DIPG) that utilize the mechanism of temporarily opening the blood-brain barrier to enhance drug delivery, such as the Focused Ultrasound (FUS) with microbubbles and neuro-navigator-controlled sonication being studied. Current treatments for DIPG primarily involve radiation therapy, and various chemotherapeutic agents have been explored, but none have been approved with a similar approach to FUS.

Phase 1

Waitlist Available

Led By Stergios Zacharoulis, MD

Research Sponsored by Columbia University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Ages 4-21 years

Subjects with evidence of clinical and/or radiographic progression of Diffuse Midline Glioma

Must not have

Subjects with documented allergy to compounds of similar chemical or biologic composition to Panobinostat or gadolinium compounds

Subjects with an uncorrectable bleeding disorder

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 90 days after the end of the last fus treatment

Awards & highlights

No Placebo-Only Group

Summary

This trial uses sound waves and tiny bubbles to temporarily open the brain's protective barrier, allowing more of the drug Panobinostat to reach brain tumors in children with a specific type of aggressive brain cancer. This method aims to improve treatment response and reduce side effects.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include reactions related to opening the blood-brain barrier such as temporary neurological changes or discomfort at sonication sites. Oral Panobinostat may cause digestive issues, fatigue, blood count changes and could affect heart rhythm.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 4 and 21 years old.

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My brain tumor is growing or spreading.

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

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I can swallow capsules.

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I am taking medication for seizures/epilepsy before my first surgery in the study.

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I am between 4 and 21 years old.

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I am mostly able to care for myself and carry out daily activities.

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I can have an MRI scan with a special dye.

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My liver and kidney functions are normal.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I have a bleeding disorder that cannot be corrected.

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I have signs of brain swelling or recent bleeding within a tumor.

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I have a brain blood vessel condition.

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I currently have an active infection.

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I have a bleeding disorder or am on blood thinners.

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My high blood pressure is not controlled by medication.

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My tumor is bleeding.

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I am using two effective birth control methods if my partner can get pregnant or if I can get pregnant.

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I have had a stroke or heart disease in the past.

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I have a spinal diffuse midline glioma.

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I cannot undergo general anesthesia due to a medical condition.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 90 days after the end of the last fus treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 90 days after the end of the last fus treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 90 days after the end of the last fus treatment for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of adverse events

Secondary study objectives

6-month Overall Survival (OS6)

6-month Progression Free Survival (PFS6)

Blood brain barrier/Tumor imaging changes

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: FUS using Oral PanobinostatExperimental Treatment2 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.

0 / 21Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The primary treatment for Diffuse Intrinsic Pontine Glioma (DIPG) is radiation therapy, which works by targeting and damaging the DNA of cancer cells, thereby inhibiting their ability to replicate and grow. This treatment can temporarily alleviate symptoms and improve quality of life. Investigational therapies, such as Focused Ultrasound (FUS) with microbubbles and neuro-navigator-controlled sonication, aim to temporarily open the blood-brain barrier (BBB). This allows for enhanced delivery of chemotherapeutic agents like Panobinostat directly to the tumor site, potentially increasing the drug's efficacy while minimizing systemic side effects. These approaches are significant for DIPG patients as they offer hope for more effective treatment options in a disease that is notoriously difficult to treat due to its location and the protective nature of the BBB.