RECRUITING

FUS Etoposide for DMG

Conditions

Diffuse Intrinsic Pontine Glioma Diffuse Midline Glioma, H3 K27M-Mutant 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 Brain Neoplasms

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Feasibility Study Examining the Use of Non-Invasive Focused Ultrasound (FUS) With Oral Etoposide Administration in Children With Progressive Diffuse Midline Glioma (DMG)

Quick Facts

Study Start:2023-06-05

Study Completion:2027-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05762419

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:4 Years to 21 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
* 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 * Prior Therapy: * Subjects 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 at least 1 week. * Subject able to give consent	* 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. * Subjects with signs of impending herniation or an acute or previous intratumoral hemorrhage * Subjects with spinal cord diffuse midline glioma * Subjects receiving a drug where CNS toxicity is reasonably suspected

Inclusion Criteria

Exclusion Criteria

* 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
* Prior Therapy:
* Subjects 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 at least 1 week.
* Subject able to give consent

* 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.
* Subjects with signs of impending herniation or an acute or previous intratumoral hemorrhage
* Subjects with spinal cord diffuse midline glioma
* Subjects receiving a drug where CNS toxicity is reasonably suspected

Contacts and Locations

Study Contact

James H Garvin, MD, PhD

CONTACT

212-305-9770

jhg1@cumc.columbia.edu

Stergios Zacharoulis, MD

CONTACT

212-305-9770

sz2764@cumc.columbia.edu

Principal Investigator

James H Garvin, MD, PhD

PRINCIPAL_INVESTIGATOR

Columbia University

Study Locations (Sites)

Columbia University Irving Medical Center

New York, New York, 10032

United States

Collaborators and Investigators

Sponsor: Columbia University

James H Garvin, MD, PhD, PRINCIPAL_INVESTIGATOR, Columbia University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-06-05

Study Completion Date2027-12

Study Record Updates

Study Start Date2023-06-05

Study Completion Date2027-12

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

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