Clinical trial NCT05615623: Blood Brain Barrier (BBB) Disruption Using Exablate Focused Ultrasound With Doxorubicin for Treatment of Pediatric DIPG
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Brain Tumor
Keywords: DIPG
Focused Utrasound
Chemotherapy
Phase I trial
Pediatrics
Lead sponsor: InSightec
Sponsor class: INDUSTRY
First posted: 2022-11-14
Enrollment: 10
Sex: ALL
Minimum age (years): 5
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DEVICE_FEASIBILITY

Brief summary: The purpose of this study is to evaluate the safety and efficacy of targeted blood brain barrier disruption with Exablate Model 4000 Type 2.0/2.1 in combination with Doxorubicin therapy for the treatment of DIPG in pediatric patients

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 a single center in Canada. 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.

Eligibility criteria: Inclusion Criteria:

* Age between 5 and 18 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
* Able to attend all study visits and with life expectancy of at least 6 months
* Able and willing to give consent and/or assent or have a legal guardian who is able and willing to do so
* If on steroids, stable or decreasing dose for at least 7 days prior to study entry
* If brain surgery occurred, at least 14 days passed since last brain surgery and the patient is fully recovered and neurologically stable

Exclusion Criteria:

* Evidence of cranial or systemic infection
* Known life-threatening systemic disease
* Previous treatment with complete cumulative doses of Doxorubicin, daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones
* Contraindication to Doxorubicin. - Known sensitivity to DEFINITY® ultrasound contrast agent or known hypersensitivity to perflutren microsphere or its components, e.g., polyethylene glycol. - Known sensitivity to gadolinium-based contrast agents
* 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
* Patients with positive HIV status. - Immunosuppression (corticosteroids to prevent/treat brain edema are permitted)
* Cerebral or systemic vasculopathy, including intracranial thrombosis, vascular malformation, cerebral aneurysm, or vasculitis
* Hypertension per age
* History of a bleeding disorder, coagulopathy or with a history of spontaneous tumour hemorrhage
* 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
* Patient receiving bevacizumab (Avastin) therapy or increasing doses of steroids
* Symptoms and signs of increased intracranial pressure
* Previous participation in other chemotherapy, molecularly targeted therapy or immunotherapy treatment-related phase 1 or 2 trials
* Tumor not visible on any pre-therapy or post-radiation imaging

Primary outcomes:
measure: Adverse Events
timeFrame: 2 years
Secondary outcomes:
measure: Blood Brain Barrier Disruption (BBBD)
timeFrame: Immediately post BBBD sonication
Other outcomes:
measure: Tumor Volume
timeFrame: Immediately post BBBD sonication
measure: Progression Free Survival (PFS) and Overall Survival (OS)
timeFrame: 2 years
Locations:
city: Toronto
country: Canada
facility: Sunnybrook Research Institute
state: Ontario
Study officials:
References: