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Exablate Blood-Brain Barrier Disruption for the Treatment of rGBM in Subjects Undergoing Carboplatin Monotherapy

Phase 1
Active, not recruiting
Conditions
Recurrent Glioblastoma
Interventions
Device: Exablate BBBD
Registration Number
NCT04417088
Lead Sponsor
InSightec
Brief Summary

The purpose of this study is to evaluate the safety and feasibility of the Exablate Model 4000 Type 2 system when used as a tool to open the blood-brain-barrier (BBB) in subjects with recurrent glioblastoma (rGBM) undergoing carboplatin monotherapy.

Detailed Description

This is a Phase 1/2, open-label, prospective, multi-center, single-arm study to establish the safety and feasibility of blood-brain-barrier disruption (BBBD) combined with intravenous carboplatin for the treatment of rGBM using the Exablate Neuro Model 4000 Type 2 system with microbubble resonators. Adult glioblastoma subjects that are planned for carboplatin chemotherapy will be considered for study enrollment. Eligible subjects will undergo up to 6 cycles of Exablate BBBD procedures in conjunction with carboplatin chemotherapy.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
30
Inclusion Criteria
  • Must be between 18-80 years old
  • Histologically confirmed glioblastoma
  • Planned for Carboplatin monotherapy
  • Be willing and able to provided written informed consent/asent
  • Tumor progression after first line chemo radiation
  • Recovered to grade 0 or 1 or pre-treatment baseline from clinically significant toxic effects of prior therapy
  • Women of childbearing potential is confirmed not pregnant. Male and Female subjects utilize highly effective contraception
  • Able to communicate verbally
Exclusion Criteria
  • Acute intracranial hemorrhage
  • Ferrous metallic implanted objects in the skull or brain
  • Prior toxicity with carboplatin chemotherapy
  • Women who are pregnant or breastfeeding
  • Cerebellar spinal cord or brain stem tumor
  • Known active Hepatitis B or Hepatitis C or HIV
  • Significant depression not adequately controlled
  • Has previously received anti-VEGF or anti-VEGF agents like Avastin
  • Cardiac disease or unstable hemodynamics
  • Severe hypertension
  • History of a bleeding disorder, coagulopathy or with a history of spontaneous tumor hemorrhage
  • Active drug or alcohol use disorder
  • Known sensitivity to gadolinium-based contrast agents
  • Known sensitivity or contraindications to ultrasound contrast agent or perflutren
  • Unable to undergo MRI or contraindications to MRI such as non-MRI compatible implanted devices
  • Difficulty lying supine and still or severe claustrophobia which cannot be managed with medication
  • Severely impaired renal function
  • Right to left or bi-directional cardiac shunt
  • Cranial or systemic infection requiring antibiotics
  • Known additional malignancy that is progression or require active treatment

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Exablate BBBD with carboplatinExablate BBBDCarboplatin will be administered via IV infusion about every 4 weeks for up to 6 cycles. The dosage will be calculated based on subject's creatinine level. On the day of planned carboplatin therapy, subjects will undergo Exablate procedure to open the blood-brain-barrier in the targeted cancerous brain areas prior to Carboplatin administration.
Exablate BBBD with carboplatinCarboplatinCarboplatin will be administered via IV infusion about every 4 weeks for up to 6 cycles. The dosage will be calculated based on subject's creatinine level. On the day of planned carboplatin therapy, subjects will undergo Exablate procedure to open the blood-brain-barrier in the targeted cancerous brain areas prior to Carboplatin administration.
Primary Outcome Measures
NameTimeMethod
Contrast intensity on MR imagingImmediately after Exablate BBBD procedure

BBBD will be determined by contrast intensity in sonicated areas on T1 weighted gadolinium-based MR imaging

Adverse eventsThrough study completion, an average of 12 months

All adverse events and/or Serious Adverse Events will be documented and reported according to CTCAE criteria.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (4)

Stanford University

🇺🇸

Palo Alto, California, United States

Cleveland Clinic

🇺🇸

Cleveland, Ohio, United States

University of Maryland

🇺🇸

Baltimore, Maryland, United States

Brigham and Women's Hospital

🇺🇸

Boston, Massachusetts, United States

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