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Glioblastoma MultiformeNCT04446416

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

A study testing NaviFUS System and Bevacizumab in people with Glioblastoma Multiforme and Glioblastoma, run by NaviFUS Corporation at 1 site in Taiwan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Glioblastoma Multiforme, Glioblastoma, Glioma
What is being tested?
NaviFUS System and Bevacizumab
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteTaiwan
Study dates
21 Jul 2020to 4 Aug 2023
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • Minimum interval since last drug therapy:
  • 1 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)
  • 4 weeks since last cytotoxic therapy
  • 6 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
  • Platelets ≥ 100,000/mm3
  • Neutrophils ≥ 1,500/mm3
  • Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
  • Urine protein creatinine (UPC) ratio < 1 or urine dipstick for proteinuria ≤ 2+
  • Alanine transaminase (ALT) < 3 ULN
  • Aspartate transaminase (AST) < 3 x ULN
  • Prothrombin time ≤ 1.2 x ULN
  • International Normalized Ratio (INR) < 1.5
  • Bilirubin < 2 x ULN
  • Patients with the region of interest (ROI) for FUS exposure are located close to the cortex with at least 20 mm distance beneath the skull bone and the ROI is not in the deep center brain with crucial brain functions, such as in the region of brain stem, or motor or speech regions
  • Patients with the potential for pregnancy and their partner must agree to use adequate contraception or be surgically sterile, or abstain from heterosexual activity starting with the first dose of treatment through at least 6 months after the last dose of BEV to avoid conception. Female patients of child-bearing potential must have a negative pregnancy test. Male patients must agree to use an adequate method of contraception starting with the first dose of treatment through 6 months after the last dose of BEV.
  • Able to give informed consent for the participation in the trial

Who cannot join

  • 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
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  • 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
  • Use of any recreational drugs or history of drug addiction
  • 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

Trial locations and contacts

1 site in 1 country.

Taiwan1 site
  • Linkou Chang Gung Memorial Hospital

    Taoyuan City, 33305

Other trials in Taiwan

About this study

Official title: An Open Label, Prospective, Pilot Study to Evaluate the Efficacy and Safety of Best Physician's Choice of Standard of Care Combined With NaviFUS System in Patients With Recurrent Glioblastoma Multiforme

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.

Read the detailed description

This trial will be divided into two stages. The study design and procedures will be as follows:

Stage 1:

Eligible patients will first be administered with BEV 10 mg/kg intravenous (IV) infusion. After 30-60 minutes, patients will receive 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 single exposure unit for up to two minutes every 2 weeks to transiently open the BBB.

After 4 weeks of treatment with BEV and single unit FUS-MB treatment, if the patient experienced BBB opening using FUS treatment and BEV IV infusion without any serious adverse effects (such as brain significant bleeding), then the patient may proceed to stage 2.

Stage 2:

Patients who complete stage 1 will enter stage 2 to receive the BEV with MB-mediated multiple units of FUS treatment for up to five minutes (but the maximum exposure time per single unit is two minutes) every 2 weeks for up to 30 weeks or until evidence of progressive disease, unacceptable toxicity, non-compliance with study follow-up, or withdrawal of consent.

After completion of study treatment, patients will be followed up for 28 days.

Being tested
NaviFUS System, Bevacizumab
Keywords
NaviFUS System, Blood-Brain Barrier, Focused Ultrasound, GBM, Bevacizumab
Medical subject headings
Glioblastoma, Glioma, Brain Neoplasms, Neoplasms, Neoplasms, Nerve Tissue

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NaviFUS SystemDevice

    Open the BBB using focused ultrasound and contrast agent SonoVue®

  • BevacizumabDrug

    Also called Avastin

    An anti-angiogenic agent to block tumor growth

Study groups in NCT04446416
Study groupRoleWhat they receive
Bevacizumab plus NaviFUS SystemExperimentalDevice: 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.
Receives: Device: NaviFUS System; Drug: Bevacizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adverse Event

    Number and severity of adverse event

    Measured: 38 weeks

  2. Progression-free survival at 6 months (PFS-6)

    Estimated rate of patients treated during 6 months without experiencing disease

    Measured: 6 months

Secondary outcomes (8)
  1. Tumor shrinkage

    The tumor shrinkage rate (TSR) by measuring the longest diameter and perpendicular diameter of the main mass on MRI scans

    Measured: 38 weeks

  2. Objective response rate (ORR)

    Proportion of subjects in the analysis population who have complete response (CR) or partial response (PR) using Radiologic Assessment in Neuro-Oncology criteria (RANO) criteria

    Measured: 38 weeks

  3. PET uptake

    The uptake of PET (as standard uptake value - SUV and tumor-to-background ratio - TBR) in tumor and in normal contralateral gray matter before start of BEV+FUS treatment will be determined.

    Measured: 38 weeks

  4. Overall survival (OS)

    OS is defined as the time in months from study treatment to death or last follow-up if alive from any cause

    Measured: 38 weeks

  5. Degree of the BBB opening

    The FUS with microbubbles can temporally open the BBB. The spatial permeability of the BBB-opened region will be assessed using dynamic contrast-enhanced MRI (DCE-MRI).

    Measured: 38 weeks

  6. Corticosteroid consumption

    Increase or decrease in corticosteroid use compared to baseline. The mean corticosteroid dosage prior to study treatment will be considered as the patient's baseline.

    Measured: 38 weeks

  7. Quality of life (QoL) assessment with the EORTC QLQ-C30

    The validated European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ-C30) will be used. The EORTC QLQ-C30 is a 30-item questionnaire. All of the response scale to questions are rated on a 4-point Likert scale from 1 = not at all, 2 = a little, 3 = quite a bit, to 4 = very much, and are linearly transformed to a 0-100 scale, with higher scores indicating more severe symptoms.

    Measured: 38 weeks

  8. Quality of life (QoL) assessment with the EORTC QLQ-BN20

    The EORTC QLQ-BN20 is a QoL assessment specific to brain neoplasms. The questionnaire includes 20 items. All of the response scale to questions are rated on a 4-point Likert scale from 1 = not at all, 2 = a little, 3 = quite a bit, to 4 = very much, and are linearly transformed to a 0-100 scale, with higher scores indicating more severe symptoms.

    Measured: 38 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Jun 2020
  2. Study start21 Jul 2020
  3. Primary completion30 Sep 2022
  4. Study completion4 Aug 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04446416
Sponsor's protocol ID
NF-2019-01
Status last verified
Apr 2026
First submitted
16 Jun 2020
Last updated
9 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 27192459
  • 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.

    PubMed 19720927
  • 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.

    PubMed 19114704
  • 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.

    PubMed 30674905
  • 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.

    PubMed 31076548
  • 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. 2026 Jul 1;99(1):149-159. doi: 10.1227/neu.0000000000003851. Epub 2025 Nov 24.

    PubMed 41283685

Questions about this trial

What is this clinical trial studying?

A study testing NaviFUS System and Bevacizumab in people with Glioblastoma Multiforme and Glioblastoma, run by NaviFUS Corporation at 1 site in Taiwan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse Event (time frame: 38 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04446416, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2026.

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