Exablate Blood-Brain Barrier Disruption With Carboplatin for the Treatment of rGBM

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. 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.

• Exablate BBBD (Device), also known as Exablate Neuro: BBB opening via Exablate Neuro Type 2 system to deliver carboplatin
• Carboplatin (Drug): Carboplatin infusion on the day of Exablate BBBD procedure to treat cancerous cells in the brain

Primary outcomes

• Occurrence of Adverse Events [Through study completion, an average of 12 months]: All adverse events and/or Serious Adverse Events will be documented and reported according to CTCAE criteria
• Contrast intensity on MR imaging [Immediately after Exablate BBBD procedure]: BBBD will be determined by contrast intensity in sonicated areas on T1 weighted gadolinium-based MR imaging

Sex: All, ages: 18 Years to 80 Years

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/assent
* Tumor progression after first line therapy
* 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
* 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