FUS Etoposide for DMG

NCT05762419 | Recruiting Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: AAAU1228
• Study Type: interventional
• Target: 10
• 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 blood brain barrier in children with progressive diffuse midline gliomas (DMG) treated with oral etoposide using focused ultrasound with microbubbles and neuro-navigator-controlled sonication. For the purpose of the study, the investigators will be opening up the blood brain barrier temporarily in one or two locations around the tumor using the non-invasive focused ultrasound technology, and administrating oral etoposide in children with progressive diffuse midline glioma.

Conditions

Diffuse Intrinsic Pontine Glioma; Diffuse Midline Glioma, H3 K27M-Mutant

Keywords

bood brain barrier; diffuse midline glioma; focused ultrasound; pontine glioma; thalamic glioma; DIPG; DMG; Glioma; Brain Diseases; Nervous System Neoplasms; Central Nervous System Neoplasm; Etoposide; Diffuse Intrinsic Pontine Glioma; Brain Neoplasms

Outcome Measures

Primary Outcomes (2)

• Number of total adverse events

  This is to evaluate the safety of using focused ultrasound to open the blood brain barrier at one or two sites for administration of etoposide in children with progressive diffuse midline glioma. Safety will be assessed by adverse events as per the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (including abnormalities from physical and neurologic examinations, laboratory values, and radiographic results).

  Up to 90 days after the end of the last focused ultrasound treatment

• Number of patients with successful opening of the blood brain barrier

  This is to evaluate the feasibility of using FUS to open the blood brain barrier at one or two sites for administration of etoposide in children with progressive diffuse midline glioma. The study defines feasibility as successful opening of the blood brain barrier.

  Treatment will consist of up to 4 cycles, each lasting 28 days. During the first 2 weeks of each cycle, subjects will receive FUS therapy for a maximum of 3 times per week, concurrent with etoposide.

Secondary Outcomes (4)

• 3-month Progression Free Survival (PFS3)

  Up to 3 months after last focused ultrasound treatment

• 3-month Overall Survival (OS3)

  Up to 3 months after last focused ultrasound treatment

• Blood brain barrier/Tumor imaging changes

  Up to 90 days after the end of the last focused ultrasound treatment

• Number of severe or serious adverse events

  Up to 90 days after the last focused ultrasound treatment

Study Arms (1)

Focused ultrasound using oral etoposide

EXPERIMENTAL

All patients enrolled in the study will be treated with oral etoposide after receiving focused ultrasound (FUS) treatment with microbubbles and neuro-navigator-controlled sonication.

Drug: Etoposide; Oral, 50 Mg; Device: Focused ultrasound with neuro-navigator-controlled sonication

Interventions

Etoposide; Oral, 50 Mg DRUG

Subjects will receive focused ultrasound sonication followed by once daily oral etoposide (50mg/m\^2/dose). Oral etoposide will be taken every day for 21 days, followed by one week of rest. For the first cycle, etoposide will be administered immediately following confirming of the blood brain barrier opening through contrast magnetic resonance imaging (MRI) which will occur within 4 hours of the focused ultrasound procedure. For subsequent cycles, etoposide will be administered immediately following the focused ultrasound procedure. Subjects may continue for a maximum of 4 cycles.

Also known as: Etoposide phosphate

Focused ultrasound using oral etoposide

Focused ultrasound with neuro-navigator-controlled sonication DEVICE

Focused ultrasound sonication will be performed a maximum of three times a week for two weeks with two weeks of rest.

Focused ultrasound using oral etoposide

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
• Radiological diagnosis of Diffuse Midline Glioma with tumor involving the pons (intrinsic, pontine based infiltrative lesion; hypointense on 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 of pontine or thalamic glioma. Subjects must have evidence of clinical and/or radiographic progression of disease.
• Lansky performance status score of at least 60 for subjects 16 years of age or younger.
• Karnofsky performance status of at least 60 for subjects greater than 16 years of age
• Organ Function:
• Adequate hematologic function defined as:
• Peripheral absolute neutrophil count ≥ 1,500/µL
• Platelet count ≥ 100,000/µL
• Partial thromboplastin time (PTT) and activated partial thromboplastin time (APTT): within normal institutional limits
• Adequate renal function defined as:
• Potassium and magnesium levels within institutional limits
• Serum creatinine below the institutional upper limit of normal (ULN) for age and gender, or creatinine clearance: ≥ 60 mL/min/1.73m2
• Adequate hepatic function defined as:
• Total bilirubin below the institutional ULN for age
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 × institutional ULN

You may not qualify if:

• Subjects that have previously received etoposide therapy
• Subjects unable to tolerate study procedures and/or anesthesia based on the opinion of the principal investigator
• Uncontrolled seizure disorder
• Pregnancy or Breast-Feeding: 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 month following their last study treatment requirement. Abstinence is an acceptable method of birth control. Women of childbearing potential will be provided a routine quantitative beta-human chorionic gonadotropin (B-hCG) test during the pre-study phase, prior to enrollment and each cycle.
• Concomitant medications: subjects who are currently receiving another investigational drug or other anti-cancer agents are not eligible.
• Screening EKG with a QTc \> 450 msec.
• Subjects with evidence of active systemic infection
• Subjects with a documented allergy to compounds of similar chemical or biologic composition to etoposide or gadolinium compounds
• Subjects with implanted metallic or electrical devices
• Subjects with uncontrollable hypertension
• Subjects with a documented bleeding disorder
• Subjects with history of structural cardiac anomalies or arrhythmias
• Subjects with history of unprovoked stroke or signs of stroke in the area of FUS target
• Subjects with SARS-CoV-2 infection requiring hospitalization in the past month and requires anticoagulation as per the Columbia University Irving Medical Center (CUIMC) institutional "Anticoagulation for COVID-19 Positive Pediatric Inpatients" guidelines (See Appendix B)
• Subjects with coagulopathy or under anticoagulant therapy.

Sponsors & Collaborators

• Columbia University: lead
• Focused Ultrasound Foundation: collaborator

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

MeSH Terms

Conditions

Diffuse Intrinsic Pontine Glioma; Glioma; Brain Diseases; Nervous System Neoplasms; Central Nervous System Neoplasms; Brain Neoplasms

Interventions

Etoposide; etoposide phosphate

Condition Hierarchy (Ancestors)

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; Neoplasms by Site; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Stergios Zacharoulis, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stergios Zacharoulis, MD

CONTACT

212-305-9770; sz2764@cumc.columbia.edu

James H Garvin, MD, PhD

CONTACT

212-305-9770; jhg1@cumc.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Herbert and Florence Irving Associate Professor of Pediatric Neuro-Oncology

Study Record Dates

• First Submitted: February 6, 2023
• First Posted: March 9, 2023
• Study Start: June 5, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)