Safety of BBB Disruption Using NaviFUS System in Recurrent Glioblastoma Multiforme (GBM) Patients

NCT03626896 | Completed DMC

• 1 other identifier: NF-2017-01
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This study is to evaluate the safety and find the tolerated ultrasound dose of transient opening of the blood-brain barrier (BBB) by using the NaviFUS System in recurrent GBM patients.

Conditions

Glioblastoma Multiforme; Brain Tumor; Glioblastoma; Glioma; Neoplasms; Neoplasms, Nerve Tissue

Keywords

BBB disruption; NaviFUS System; Focused Ultrasound; GBM

Outcome Measures

Primary Outcomes (1)

• Number and severity of AE

  Safety of transient opening of the BBB by using the NaviFUS System

  45 days

Secondary Outcomes (2)

• Tolerated dose of FUS with the NaviFUS System for transient disruption of the BBB

  7 days post-FUS

• Quantify the BBB disruption following BBB disruption by the NaviFUS System

  1 day

Study Arms (1)

NaviFUS System

EXPERIMENTAL

NaviFUS System: dose escalation focus ultrasound to transiently disrupt BBB

Device: NaviFUS System

Interventions

NaviFUS System DEVICE

BBB Disruption by FUS in recurrent GBM Other Name: Neuronavigation-guided focus ultrasound system

NaviFUS System

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients diagnosed with recurrent GBM and will undergo surgery
• Able to give written informed consent for the participation in the trial
• Adult male/female patients \> 20 years of age
• Patients if already on radiotherapy, a gap of 7 days shall be maintained between the last day of radiotherapy and the day of screening
• Patients if already on the steroids treatment, then should be on a stable dose of steroids for at least 7 days prior to screening
• Body mass index (BMI) ≥17 kg / m2
• Patients with life expectancy ≥ 3 months
• Able to comply with study requirements in the opinion of the investigator
• Adequate hepatic, renal, coagulation, and hematopoietic function
• Hemoglobin ≥ 10 g/dL
• Platelets ≥ 100,000/mm3
• Neutrophils ≥ 1,500/mm3
• Normal creatinine clearance ≥ 50mL/min
• Alanine transaminase (ALT) \< 3 x upper limit of normal (ULN)
• Aspartate transaminase (AST) \< 3 x ULN

You may not qualify if:

• Patients at screening visit have arteriovenous malformation (AVM) or cerebral aneurysm
• Use of any recreational drugs or history of drug addiction
• Pregnant or breast-feeding women
• The receipt of an investigational drug, or participation in a drug research study within a period of one month prior to the first FUS exposure
• Known sensitivity/allergy to MRI contrast agents, CT contrast agents, SonoVue®, or any of its components
• Any other condition that, in the investigator's judgment, might increase the risk to the patients or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study
• Abnormal baseline findings considered by the investigator to indicate conditions that might affect study endpoints
• Patients who have hemorrhage or cyst within the ROI
• Severe hypertension at screening (diastolic blood pressure \> 100 mmHg on medication)
• Receiving anticoagulant (e.g. warfarin) or antiplatelet (e.g. aspirin) therapy within one week prior to study treatment or drugs known to increase risk or hemorrhage (e.g. Avastin) within one month prior to study treatment

Sponsors & Collaborators

• NaviFUS Corporation: lead
• Chang Gung Memorial Hospital: collaborator

Study Sites (1)

Linkou Chang Gung Memorial Hospital

Taoyuan, 33305, Taiwan

Location

Related Publications (5)

• Wei KC, Tsai HC, Lu YJ, Yang HW, Hua MY, Wu MF, Chen PY, Huang CY, Yen TC, Liu HL. Neuronavigation-guided focused ultrasound-induced blood-brain barrier opening: a preliminary study in swine. AJNR Am J Neuroradiol. 2013 Jan;34(1):115-20. doi: 10.3174/ajnr.A3150. Epub 2012 Jun 21.

  PMID: 22723060 BACKGROUND

• McDannold N, Zhang Y, Vykhodtseva N. Blood-brain barrier disruption and vascular damage induced by ultrasound bursts combined with microbubbles can be influenced by choice of anesthesia protocol. Ultrasound Med Biol. 2011 Aug;37(8):1259-70. doi: 10.1016/j.ultrasmedbio.2011.04.019. Epub 2011 Jun 8.

  PMID: 21645965 BACKGROUND

• Liu HL, Wai YY, Chen WS, Chen JC, Hsu PH, Wu XY, Huang WC, Yen TC, Wang JJ. Hemorrhage detection during focused-ultrasound induced blood-brain-barrier opening by using susceptibility-weighted magnetic resonance imaging. Ultrasound Med Biol. 2008 Apr;34(4):598-606. doi: 10.1016/j.ultrasmedbio.2008.01.011. Epub 2008 Mar 3.

  PMID: 18313204 BACKGROUND

• Hynynen K, McDannold N, Sheikov NA, Jolesz FA, Vykhodtseva N. Local and reversible blood-brain barrier disruption by noninvasive focused ultrasound at frequencies suitable for trans-skull sonications. Neuroimage. 2005 Jan 1;24(1):12-20. doi: 10.1016/j.neuroimage.2004.06.046.

  PMID: 15588592 BACKGROUND

• Wei KC, Chu PC, Wang HY, Huang CY, Chen PY, Tsai HC, Lu YJ, Lee PY, Tseng IC, Feng LY, Hsu PW, Yen TC, Liu HL. Focused ultrasound-induced blood-brain barrier opening to enhance temozolomide delivery for glioblastoma treatment: a preclinical study. PLoS One. 2013;8(3):e58995. doi: 10.1371/journal.pone.0058995. Epub 2013 Mar 19.

  PMID: 23527068 BACKGROUND

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms; Glioma; Neoplasms; Neoplasms, Nerve Tissue

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Kuo-Chen Wei, M.D.

  Chang Gung Memorial Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DEVICE FEASIBILITY
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2018
• First Posted: August 13, 2018
• Study Start: August 17, 2018
• Primary Completion: May 20, 2019
• Study Completion: June 19, 2019
• Last Updated: June 21, 2019

Record last verified: 2018-08

Locations

TW (1)