Blood Brain Barrier (BBB) Disruption Using Exablate Focused Ultrasound With Doxorubicin for Treatment of Pediatric DIPG

Sponsor
InSightec (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05630209
Collaborator
(none)
10
1
1
35
0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of targeted blood brain barrier disruption with Exablate Model 4000 Type2.0/2.1 in combination with Doxorubicin therapy for the treatment of DIPG in pediatric patients

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

This is a prospective, single arm, non-randomized feasibility study to evaluate the safety, feasibility and preliminary efficacy of Blood Brain Barrier Disruption (BBBD) using the Exablate Type 2 system in pediatric patients with Diffuse Intrinsic Pontine Gliomas (DIPG)undergoing Doxorubicin chemotherapy. The study will be conducted at up to three sites in the United States. Patients will undergo 3 treatment cycles, approximately 4 -6 weeks apart. The study aims to establish feasibility and safety of Exablate BBBD in conjunction with Doxorubicin in the treatment of pediatric DIPG and assess preliminary efficacy in this patient population.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
10 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Device Feasibility
Official Title:
A Safety and Feasibility Study to Evaluate Blood Brain Barrier Disruption Using Exablate MR Guided Focused Ultrasound in Combination With Doxorubicin in Treating Pediatric Patients With Diffuse Intrinsic Pontine Gliomas (DIPG)
Anticipated Study Start Date :
Feb 1, 2023
Anticipated Primary Completion Date :
Jan 1, 2025
Anticipated Study Completion Date :
Jan 1, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: Blood Brain Barrier Disruption (BBBD)

Exablate MR Guided Focused Ultrasound for Blood Brain Barrier Disruption with Doxorubicin for treating pediatric patients with DIPG

Device: Exablate
Blood Brain Barrier Disruption (BBBD) via Exablate Type 2 system with microbubble resonators on the day of Doxorubicin infusion to treat DIPG brain tumors
Other Names:
  • Exablate BBBD
  • Drug: Doxorubicin
    Doxorubicin infusion
    Other Names:
  • Adriamycin
  • Rubex
  • Outcome Measures

    Primary Outcome Measures

    1. Adverse Events [2 years]

      All adverse events from first treatment to end of study will be documented and reported according to the CTCAE terminology and severity scale

    Secondary Outcome Measures

    1. Blood Brain Barrier Disruption (BBBD) [immediately post BBBD sonication]

      BBBD will be assessed as a comparative ratio measured in pre and post-sonication contrast-enhanced MR images

    Other Outcome Measures

    1. Progression Free Survival (PFS) [2 years]

      PFS will be assessed based on the Response Assessment in Pediatric Neuro-Oncology (RAPNO) scale.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    5 Years to 21 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Age between 5 and 21 years, inclusive

    • Patient diagnosed with DIPG

    • At least 4-week and not greater than 12 weeks from completion of radiation therapy

    • Post-radiation imaging does not show evidence of necrosis/ hemorrhage or other features that contraindicate MRgFUS

    • If brain surgery occurred, at least 14 days passed since last brain surgery and the patient is fully recovered and neurologically stable

    • If on steroids, stable or decreasing dose for at least 7 days prior to study entry

    • Stable or improving neurologic status for 7 days prior to study entry

    • Able and willing to give consent and/or assent or have a legal guardian who is able and willing to do so

    • Able to attend all study visits and with life expectancy of at least 6 months

    Exclusion Criteria:
    • Tumor not visible on any pre-therapy or post-radiation imaging

    • Previous participation in other chemotherapy, molecularly targeted therapy, or immunotherapy treatment-related phase 1 or 2 trials

    • Symptoms and signs of increased intracranial pressure

    • Subject with metastatic disease

    • Subject with ventricular peritoneal shunt

    • Subject receiving bevacizumab (Avastin) therapy or increasing doses of steroids

    • Anti-coagulant therapy, or medications known to increase risk of hemorrhage, (e.g., ASA, non-steroidal anti-inflammatory drugs [NSAIDs], statins) within washout period prior to treatment

    • History of a bleeding disorder, coagulopathy or with a history of spontaneous tumor hemorrhage.

    • Hypertension per age

    • Cerebral or systemic vasculopathy, including intracranial thrombosis, vascular malformation, cerebral aneurysm, or vasculitis

    • Immunosuppression (corticosteroids to prevent/treat brain edema are permitted).

    • Patients with positive HIV status

    • Active seizure disorder or epilepsy (seizures despite medical treatment) for a minimum of 4 weeks prior to first cycle/Exablate BBBD procedure captured by history

    • Known sensitivity to gadolinium-based contrast agents

    • Known sensitivity to DEFINITY┬« ultrasound contrast agent or known hypersensitivity to perflutren microsphere or its components, e.g., polyethylene glycol

    • Contraindication to Doxorubicin

    • Previous treatment with complete cumulative doses of Doxorubicin, daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones

    • Severely impaired renal function with estimated glomerular filtration rate <2 standard deviations for age

    • Patients that may require trastuzumab during the study

    • Patients that may require inhibitors and inducers of CYP3A4, CYP2D6, and/or P-gp during the study

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Children's National Medical Center Washington District of Columbia United States 20010

    Sponsors and Collaborators

    • InSightec

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    InSightec
    ClinicalTrials.gov Identifier:
    NCT05630209
    Other Study ID Numbers:
    • BT016
    First Posted:
    Nov 29, 2022
    Last Update Posted:
    Jan 6, 2023
    Last Verified:
    Jan 1, 2023
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    Yes
    Keywords provided by InSightec
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jan 6, 2023