Efficacy and Safety of NaviFUS System add-on Bevacizumab (BEV) in Recurrent GBM Patients

NCT04446416 | Completed DMC

• 1 other identifier: NF-2019-01
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single-arm, two stages, open-label, pilot study to investigate the efficacy and safety of FUS add-on bevacizumab (BEV) in rGBM patients. The BEV is the best physician's choice of standard of care for rGBM after prior radiotherapy and temozolomide chemotherapy in the LinKou Chang Gung Memorial Hospital. Eligible patients will be enrolled through the process of informed consent.

Conditions

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

Keywords

NaviFUS System; Blood-Brain Barrier; Focused Ultrasound; GBM; Bevacizumab

Outcome Measures

Primary Outcomes (2)

• Adverse Event

  Number and severity of adverse event

  38 weeks

• Progression-free survival at 6 months (PFS-6)

  Estimated rate of patients treated during 6 months without experiencing disease

  6 months

Secondary Outcomes (8)

• Tumor shrinkage

  38 weeks

• Objective response rate (ORR)

  38 weeks

• PET uptake

  38 weeks

• Overall survival (OS)

  38 weeks

• Degree of the BBB opening

  38 weeks

Study Arms (1)

Bevacizumab plus NaviFUS System

EXPERIMENTAL

Device: NaviFUS System BBB Disruption by FUS in recurrent GBM Microbubbles (MB) (SonoVue®) 0.1 mL/kg and optimal ultrasound exposure doses (based on the acoustic emission feedback FUS power control algorithm) generated from the NaviFUS System every 2 weeks to transiently open the BBB. Drug: Bevacizumab 10 mg/kg every 2 weeks for up to 36 weeks or until evidence of progressive disease, unacceptable toxicity, non-compliance with study follow-up, or withdrawal of consent.

Device: NaviFUS System; Drug: Bevacizumab

Interventions

NaviFUS System DEVICE

Open the BBB using focused ultrasound and contrast agent SonoVue®

Bevacizumab plus NaviFUS System

Bevacizumab DRUG

An anti-angiogenic agent to block tumor growth

Also known as: Avastin

Bevacizumab plus NaviFUS System

Eligibility Criteria

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

You may qualify if:

• Adult male/female patients ≥ 20 years of age
• Patients with histologically confirmed glioblastoma, recurrent after prior radiotherapy and temozolomide chemotherapy.
• Patient may have been operated for recurrence. If operated: with measurable residual tumor
• Minimum interval since completion of radiation treatment is 12 weeks
• Patients if already on the steroids then should be on a stable dose of steroids for at least 7 days prior to study treatment
• Body mass index (BMI) ≥17 kg / m2
• Minimum interval since last drug therapy:
• week for non-cytotoxic agents (e.g., interferon, tamoxifen), daily chemotherapy (e.g., metronomic temozolomide, cytoxan) or targeted therapies administered daily (e.g., gleevec, tarceva)
• weeks since last cytotoxic therapy
• weeks since the completion of a nitrosourea-containing chemotherapy regimen (e.g., carmustine (BCNU))
• Patients with life expectancy ≥ 3 months
• The Karnofsky performance status (KPS) in the patient must be \> 60
• Eastern Cooperative Oncology Group (ECOG) Score ≤ 2
• Adequate hepatic, renal, coagulation, and hematopoietic function
• Hemoglobin ≥ 8 g/dL

You may not qualify if:

• Patients who have had previous treatment with an inhibitor of vascular endothelial growth factor (VEGF) or VEGFR (including bevacizumab)
• New York Heart Association (NYHA) Grade II or greater congestive heart failure requiring hospitalization within 12 months prior to screening
• Severe hypertension at screening (diastolic blood pressure \> 100 mmHg on medication)
• Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, severe cerebral or myocardial infarction, cardiac shunt, heart attack within the previous 12 months, stroke (except for transient ischemic attack; TIA) within the previous 6 months, or psychiatric illness/social situations that would limit compliance with study requirements
• Unstable pulmonary disease or Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of screening
• Implanted pacemaker, defibrillator or deep brain stimulator, other implanted electronic devices in the brain or documented clinically significant arrhythmias
• Major surgery such as intra-thoracic, intra-abdominal or intra-pelvic (with the exception of craniotomy), open biopsy or significant traumatic injury ≤ 4 weeks prior to screening, or patients who have had minor procedures, percutaneous biopsies or placement of vascular access device ≤ 1 week prior to screening, or who have not recovered from side effects of such procedure or injury
• Known HIV positive patients, however, that HIV testing is not required for entry into this study
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of screening
• Receiving anticoagulant (e.g. warfarin) or antiplatelet (e.g. aspirin) therapy within one week prior to beginning treatment
• Pregnant or breast-feeding women
• Known sensitivity/allergy to PET tracers, Magnetic Resonance Imaging (MRI) contrast agents, Computer Tomography (CT) contrast agents, SonoVue®, bevacizumab, or any of their components
• Abnormal baseline findings considered by the investigator to indicate conditions that might affect study endpoints
• Patients who have hemorrhage or cyst within the ROI
• The receipt of an investigational drug within a period of 4 weeks prior to the first FUS exposure

Sponsors & Collaborators

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

Study Sites (1)

Linkou Chang Gung Memorial Hospital

Taoyuan, 33305, Taiwan

Location

Related Publications (6)

• Liu HL, Hsu PH, Lin CY, Huang CW, Chai WY, Chu PC, Huang CY, Chen PY, Yang LY, Kuo JS, Wei KC. Focused Ultrasound Enhances Central Nervous System Delivery of Bevacizumab for Malignant Glioma Treatment. Radiology. 2016 Oct;281(1):99-108. doi: 10.1148/radiol.2016152444. Epub 2016 May 18.

  PMID: 27192459 BACKGROUND

• Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R, Vredenburgh J, Huang J, Zheng M, Cloughesy T. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009 Oct 1;27(28):4733-40. doi: 10.1200/JCO.2008.19.8721. Epub 2009 Aug 31.

  PMID: 19720927 BACKGROUND

• Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, Garren N, Mackey M, Butman JA, Camphausen K, Park J, Albert PS, Fine HA. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol. 2009 Feb 10;27(5):740-5. doi: 10.1200/JCO.2008.16.3055. Epub 2008 Dec 29.

  PMID: 19114704 BACKGROUND

• Mainprize T, Lipsman N, Huang Y, Meng Y, Bethune A, Ironside S, Heyn C, Alkins R, Trudeau M, Sahgal A, Perry J, Hynynen K. Blood-Brain Barrier Opening in Primary Brain Tumors with Non-invasive MR-Guided Focused Ultrasound: A Clinical Safety and Feasibility Study. Sci Rep. 2019 Jan 23;9(1):321. doi: 10.1038/s41598-018-36340-0.

  PMID: 30674905 BACKGROUND

• Sonabend AM, Stupp R. Overcoming the Blood-Brain Barrier with an Implantable Ultrasound Device. Clin Cancer Res. 2019 Jul 1;25(13):3750-3752. doi: 10.1158/1078-0432.CCR-19-0932. Epub 2019 May 10.

  PMID: 31076548 BACKGROUND

• Chen KT, Tsai HC, Huang CY, Liau CT, Ho KC, Toh CH, Chuang CC, Hsu PW, Huang YC, Chang TW, Yeap MC, Chen PY, Lee CC, Lin YJ, Feng LY, Airan RD, Li G, Lim M, Liu HL, Wei KC. Combination of Neuronavigation-Guided Focused Ultrasound and Bevacizumab for Patients With Recurrent Glioblastoma: A Pilot Study. Neurosurgery. 2025 Nov 24. doi: 10.1227/neu.0000000000003851. Online ahead of print.

  PMID: 41283685 BACKGROUND

MeSH Terms

Conditions

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

Interventions

Bevacizumab

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

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: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2020
• First Posted: June 24, 2020
• Study Start: July 21, 2020
• Primary Completion: September 30, 2022
• Study Completion: August 4, 2023
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)