FUS Etoposide for DMG
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age4-21
SponsorColumbia University
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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.
Trial design
Design model
Single group
Treatments tested in this trial
Etoposide; Oral, 50 Mg
DrugSubjects 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.
Focused ultrasound with neuro-navigator-controlled sonication
DeviceFocused ultrasound sonication will be performed a maximum of three times a week for two weeks with two weeks of rest.
Treatment groups
10 Participants
are divided into 1 treatment groupGroup A: Focused ultrasound using oral etoposideExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
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).
Time frame
Up to 90 days after the end of the last focused ultrasound treatment2
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.
Time frame
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
1
3-month Progression Free Survival (PFS3)
Progression Free Survival is defined as the duration of the time from the start of focused ultrasound treatment to time of progression or death from any cause, whichever occurs first. Patient's vitality status will be monitored with a monthly follow-up phone call for 3 months post-treatment.
Time frame
Up to 3 months after last focused ultrasound treatment2
3-month Overall Survival (OS3)
Overall survival is defined as the duration of time from the start of focused ultrasound treatment to death from any cause. Overall survival will be measured by follow-up with a study participant every 3-6 months until death for any reason. Patient's vitality status will be monitored with a monthly follow-up phone call for 3 months post-treatment.
Time frame
Up to 3 months after last focused ultrasound treatment3
Blood brain barrier/Tumor imaging changes
MRI and other radiological evidence to show successful BBB opening and closing
Time frame
Up to 90 days after the end of the last focused ultrasound treatment4
Number of severe or serious adverse events
All severe adverse events (SAEs), and adverse events (AEs), grade 3 and higher (except for thrombocytopenia which will include grade 2) will be collected and reported on each patient over the course of their treatment, according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. All SAEs and any AEs grade 3 and higher (except for thrombocytopenia which will include grade 2) will be tallied.
Time frame
Up to 90 days after the last focused ultrasound treatmentSponsors and contacts
Click on the lead sponsor to view all of their trials.
Columbia University
Lead sponsor
Focused Ultrasound Foundation
Collaborator
Source ClinicalTrials.gov