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

• ClinicalTrials.gov Identifier: NCT04417088
• Recruitment Status: Active, not recruiting
• First Posted: June 4, 2020
• Last Update Posted: March 5, 2024
• Sponsor: InSightec
• Information provided by (Responsible Party): InSightec

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Recurrent Glioblastoma	Drug: Carboplatin; Device: Exablate BBBD	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Assessment of Safety and Feasibility of Exablate Type 2 for Blood-Brain Barrier Disruption (BBBD) With Microbubble Resonators for the Treatment of Recurrent Glioblastoma (rGBM) in Subjects Undergoing Carboplatin Monotherapy
• Actual Study Start Date: November 6, 2020
• Actual Primary Completion Date: December 31, 2023
• Estimated Study Completion Date: July 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Exablate BBBD with carboplatin; Carboplatin 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.	Drug: Carboplatin; Carboplatin infusion on the day of Exablate BBBD procedure to treat cancerous cells in the brain; Device: Exablate BBBD; BBB opening via Exablate Neuro Type 2 system with microbubble resonators.; Other Name: Exablate Neuro

Outcome Measures

Primary Outcome Measures :

1. Adverse events [ Time Frame: 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.
2. Contrast intensity on MR imaging [ Time Frame: Immediately after Exablate BBBD procedure ]
   BBBD will be determined by contrast intensity in sonicated areas on T1 weighted gadolinium-based MR imaging

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

Stanford University

Palo Alto, California, United States, 94304

United States, Maryland

University of Maryland

Baltimore, Maryland, United States, 21201

United States, Massachusetts

Brigham and Women's Hospital

Boston, Massachusetts, United States, 02115

United States, Ohio

Cleveland Clinic

Cleveland, Ohio, United States, 44195

Sponsors and Collaborators

InSightec

More Information

• Responsible Party: InSightec
• ClinicalTrials.gov Identifier: NCT04417088
• Other Study ID Numbers: BT009
• First Posted: June 4, 2020
• Last Update Posted: March 5, 2024
• Last Verified: March 2024

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by InSightec:

Exablate; Focused Ultrasound; rGBM

Additional relevant MeSH terms:

Glioblastoma; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Carboplatin; Antineoplastic Agents