Glioblastoma MultiformePhase 3NCT06496971

A Prospective Pivotal Study to Evaluate the Efficacy and Safety of Avastin® Bevacizumab (BEV) With or Without Microbubble-mediated Focused Ultrasound (FUS-MB) Using NaviFUS System in Recurrent Glioblastoma Multiforme Patients

A Phase 3 study testing Bevacizumab, Microbubble and Low-Intensity Focused Ultrasound in people with Glioblastoma Multiforme and Glioblastoma, run by NaviFUS Corporation at 2 sites in Taiwan.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial summary

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Glioblastoma Multiforme, Glioblastoma, Glioblastoma Multiforme, Adult
What is being tested?: Bevacizumab, Microbubble and Low-Intensity Focused Ultrasound
Type of treatment: Injection or infusion, Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 32 participants
Where: 2 sitesTaiwan
Study dates: 8 Nov 2024to 31 Mar 2027
Phase: Phase 3
Are there results?: Not yet: the study is under way

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 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female patients ≥ 18 years of age at the time of study enrollment.
Body mass index (BMI) ≥ 17 kg/m2.
Patients diagnosed with glioblastoma must have unequivocal evidence of recurrence, as determined by contrast-enhanced magnetic resonance imaging (CE-MRI), following prior radiotherapy and temozolomide chemotherapy.
Patients may have undergone surgery for recurrence. The patients should have completed surgery and adequately recovered prior to the time of study enrollment.
Patients must have radiographic evidence of either at least an 80% resection of enhancing tumor following recurrence or a maximal measurable residual tumor ≤ 20 cm3.
If patients are receiving corticosteroids, they must have been on a stable or decreasing dose of corticosteroids for at least 1 week prior to the planned first treatment.

Show all 31Show fewer

At the time of study enrollment, the minimum interval since the last event:
4 weeks out from invasive procedures (e.g., open biopsy, surgical resection, significant traumatic injury, or any other major surgery involving entry into a body cavity) and the patient must have recovered from the effects of surgery
1 week out from minor surgical procedures or core biopsies
Patients must have recovered from the toxic effects of prior therapy at the time of study enrollment as follows:
4 weeks out from any investigational drug or device
4 weeks out from chemotherapy
6 weeks since the completion of a nitrosourea-containing chemotherapy regimen (e.g., Carmustine (BCNU))
12 weeks out from completion of radiotherapy
Patients should have a life expectancy ≥ 12 weeks.
Patients must have Karnofsky Performance Status (KPS) ≥ 70.
Adequate hematopoietic, renal, hepatic, and coagulation function, defined as:
Hemoglobin ≥ 10 g/dL
Platelets ≥ 100,000/mm3
Neutrophils ≥ 1,500/mm3
Serum creatinine ≤ 1.5 × upper limit of normal (ULN)
Urine protein creatinine ratio (UPCR) < 1 or urine dipstick for proteinuria ≤ 2+
Alanine aminotransferase (ALT) < 3 × ULN
Aspartate aminotransferase (AST) < 3 × ULN
Total bilirubin (TBL) < 2 × ULN
Prothrombin time ≤ 1.5 x ULN
International Normalized Ratio (INR) < 1.5 These tests must be conducted within 2 weeks prior to the planned first treatment.
The central of FUS exposure region is located with a minimum distance of at least 30 mm beneath the skull bone.
Females of childbearing potential must have a negative pregnancy test documented within 2 weeks prior to first treatment. Females of childbearing potential and male patients with partners of childbearing potential must agree to adhere to an acceptable method of contraception (as outlined below) from prior to the first study treatment until at least 6 months after the completion of last treatment. Standard acceptable methods of contraception include the use of highly effective methods such as hormonal contraception, diaphragm, cervical cap, vaginal sponge, condom, spermicide, vasectomy, intrauterine device, or abstinence from sexual activity.
Patients are able and willing to have peripheral intravenous (IV) line placement of Bevacizumab and are able to have hair shaved (either whole head or in the region where the coupling membrane will touch) prior to FUS treatment if assigned to treatment group.
Patients or their legal representatives are able to provide written informed consent for participation in the trial and patients are willing to comply the procedures (i.e., study-related assessments), instructions, and restrictions outlined in this study in the duration of the study. Informed consent should also be given for biological materials and diagnostic imaging to be stored and used for future research on brain tumors.

Who cannot join

Patients who have radiographic evidence of multifocal enhancing tumors.
Patients who have undergone previous treatment with anti-angiogenic therapy, including Bevacizumab, or other VEGF inhibitors or VEGF-receptor signaling inhibitors.
Patients who have previously received Carmustine wafers implantation during re-operation.
Patients who have previously received or are currently undergoing tumor treating fields (TTF) treatment.
Uncontrolled or significant cardiovascular disease, including any of the following:
New York Heart Association (NYHA) Grade II or above congestive heart failure (CHF) within 12 months prior to study enrollment

Show all 27Show fewer

Unstable angina pectoris
Medical history of myocardial infarction within 6 months prior to study enrollment
Cardiac shunt
Stroke (except for transient ischemic attack; TIA) within 6 months prior to study enrollment.
Patients with implanted electronic device, for example, implanted cardioverter-defibrillator (ICD), cardiac pacemaker, permanent medication pumps, cochlear implants, responsive neurostimulator (RNS), deep brain stimulation (DBS), or other electronic devices implanted in the brain. Patients with contraindications for MRI as judged by Investigator, including non-MRI compatible metallic implant(s).
Patients with inadequately controlled hypertension, defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg while on medication, within 2 weeks prior to first treatment.
Patients with evidence of any thrombotic or hemorrhagic events, including but not limited to:
Inherited bleeding diathesis or significant coagulopathy with the risk of bleeding (i.e., in the absence of therapeutic anticoagulation).
History of pulmonary haemorrhage/haemoptysis ≥ grade 2 according to the CTCAE version 5.0 criteria within 1 month prior to study enrollment
Arterial or venous thrombosis (e.g., pulmonary embolism) within 3 months prior to study enrollment
Patients with unstable pulmonary disease or chronic obstructive pulmonary disease (COPD) exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of study enrollment.
Patients who have psychiatric illness/social situations that would limit compliance with study requirements.
Known HIV-positive patient, however, that HIV testing is not required for entry into this study.
Acute bacterial or fungal infection requiring intravenous antibiotics at the time of study enrollment.
History or evidence of active gastroduodenal ulcer, gastrointestinal perforations/fistula, or intra-abdominal abscess within 6 months prior to study enrollment.
Receiving anticoagulant (e.g., warfarin or LMW heparin) or antiplatelet (e.g., aspirin) therapy within 1 week prior to beginning treatment.
Known sensitivity/allergy to Magnetic Resonance Imaging (MRI) contrast agents, Computer Tomography (CT) contrast agents, SonoVue®, Bevacizumab, or any of their components.
Pregnant (positive pregnancy test) or breast-feeding women.
Use of any recreational drugs or history of drug addiction.
Other severe concurrent and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection, uncontrolled epilepsy, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol.
Any other condition that, in the Investigator's discretion, might increase the risk to the patients or compromise the evaluation of the clinical trial endpoints.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Sheang-Tze Fung, Ph.D. contact

02-25860560 ext. 167

stfung@navifus.com

Arthur Lung, Ph.D. contact

arthur.lung@navifus.com

Taiwan2 sites, 2 recruiting

National Taiwan University Hospital
Taipei, 10048
Dar-Ming Lai, M.D., Ph.D., dmlai@ntu.edu.tw
Recruiting
Linkou Chang Gung Memorial Hospital
Taoyuan, 33305
Kuo-Chen Wei, M.D., kuochenwei@cgmh.org.tw
Recruiting

Other trials in Taiwan

About this study

Official title: A Prospective, Randomized, Standard of Care Controlled, Parallel, Open-Label, Multicenter Pivotal Study to Evaluate the Efficacy and Safety of Avastin® in Combination With NaviFUS System Compared With Avastin® Alone for the Treatment of Recurrent Glioblastoma Multiforme (rGBM)

This will be a prospective, randomized, standard of care (SoC) controlled, parallel, open-label, multicenter pivotal study to investigate the efficacy and safety of Bevacizumab (BEV) in combination with or without microbubble (MB)-mediated FUS in patients with recurrent GBM. BEV represents the physician's best choice for the standard of care in rGBM after previous treatment with surgery (if appropriate), standard radiotherapy with temozolomide chemotherapy, and with adjuvant temozolomide.

Read the detailed description

The study aims to compare the efficacy of combining Bevacizumab with NaviFUS System relative to Bevacizumab alone in patients with rGBM who have previously undergone radiotherapy and temozolomide chemotherapy.

Any patient with a histological diagnosis of GBM who meets all of the specific eligibility criteria may participate in this study by signing informed consent in person or through their legal representative. Eligible patients will undergo a 2-week baseline observation screening period.

Up to 32 evaluable patients will be recruited in this study. Eligible patients will be randomized in a 1:1 ratio, with one group receiving the standard of care (SoC) BEV alone and the other group receiving treatment with microbubble-mediated FUS treatment in addition to BEV (FUS-MB+BEV).

Eligible patients who assigned to the SoC group will follow the standard operating procedures of BEV (10 mg/kg intravenous (IV) infusion over 30-90 minutes). On the other hand, eligible patients assigned to treatment group will initially receive the same BEV schedule. After at least 30 minutes, patients will be administered microbubbles (MB) (SonoVue® ) at a dose of 0.1 mL/kg, along with optimal ultrasound exposure doses determined by the acoustic emission feedback FUS power control algorithm of the NaviFUS System. The treatment will be administered every 2 weeks up to 34 weeks or until evidence of progression disease (PD), intolerable toxicity precluding further treatment, non- compliance with study follow-up, or withdrawal of consent, whichever occurs first.

Conditions: Glioblastoma Multiforme, Glioblastoma, Glioblastoma Multiforme, Adult, Glioma, Brain Tumor, Brain Tumor, Recurrent
Being tested: Bevacizumab, Microbubble, Low-Intensity Focused Ultrasound
Keywords: NaviFUS System, Blood-Brain Barrier Opening, Focused Ultrasound, FUS, Low-Intensity Focused Ultrasound, LIFU, Bevacizumab, BEV, Avastin
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.

BevacizumabDrug
Also called Avastin
An anti-angiogenic agent to block tumor growth
MicrobubbleDrug
Also called SonoVue
Open the Blood-Brain Barrier (BBB) using focused ultrasound and microbubble
Low-Intensity Focused UltrasoundDevice
Also called NaviFUS System
Open the Blood-Brain Barrier (BBB) using focused ultrasound and microbubble

Study groups in NCT06496971
Study group	Role	What they receive
Standard of care (SoC) BEV alone	Active comparator	SoC group will follow the standard operating procedures of BEV (10 mg/kg intravenous (IV) infusion over 30-90 minutes, following the instructions in the drug package insert). Receives: Drug: Bevacizumab
Microbubble-mediated FUS treatment with BEV (FUS-MB+BEV)	Experimental	FUS-MB+BEV group will follow the standard operating procedures of BEV (10 mg/kg intravenous (IV) infusion over 30-90 minutes, following the instructions in the drug package insert). After at least 30 minutes, patients will be administered microbubbles (MB) (SonoVue® ) at a dose of 0.1 mL/kg, along with optimal ultrasound exposure doses determined by the acoustic emission feedback FUS power control algorithm of the NaviFUS System. Receives: Drug: Bevacizumab; Drug: Microbubble; Device: Low-Intensity Focused Ultrasound

What is being measured

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

6-month progression-free survival (PFS-6) of Bevacizumab (BEV) with or without microbubble-mediated focused ultrasound (FUS-MB) using NaviFUS System
PFS-6 will be estimated the proportion of patients who remain progression-free at the 6-month time point, based on Response Assessment in Neuro-Oncology (RANO) Criteria, from the time of randomization.
Measured: Up to 6 months

Secondary outcomes (13)

12-month progression-free survival (PFS-12)
PFS-12 will be estimated the proportion of patients who remain progression-free at the 12-month time point, based on Response Assessment in Neuro-Oncology (RANO) Criteria, from the time of randomization.
Measured: Up to 12 months
Progression-free survival time (PFS)
PFS is defined as the time from the date of randomization to the earliest date of the first objective documentation of radiographic progression disease based on RANO Criteria, death, or last known follow-up due to any cause whichever occurs first. PFS will be followed continuously till the End-of-Study.
Measured: Up to 62 weeks
One- and Two-year survival rates
One- and Two-year survival rates will be estimated the proportion of patients who remain alive at the one-year and two-year time points from the time of randomization.
Measured: Up to 12 and 24 months
Overall survival (OS)
OS is defined as the time from the date of randomization to the earliest date of death or last known follow-up due to any cause whichever occurs first. OS will be followed continuously while subjects are on study and the survival follow-up phase of the study.
Measured: Up to 36 months
Objective response rate (ORR)
ORR is defined as the proportion of patients who achieved a best overall response of complete response (CR) or partial response (PR) based on a combination of imaging and clinical features as assessed by the RANO Criteria.
Measured: Up to 62 weeks
Clinical benefit rate (CBR)
CBR is defined as the proportion of patients who achieved an overall response of CR, PR, or stable disease (SD) based on a combination of imaging and clinical features as assessed by the RANO Criteria.
Measured: Up to 62 weeks
Local disease control on the MRI Images
Local disease control is defined as the proportion of patients who achieved a CR, PR, or SD within the planning target tumor lesion, as assessed by the RANO Criteria. Progressive disease (PD) is defined as the presence of at least two sequential CE-MRI scans, separated by a ≥ 4 weeks interval, exhibiting local tumor progression at the treatment site, with distant recurrence or new lesion(s) not included in the assessment. The target tumor lesion on the MRI images will be assessed at baseline and throughout treatment period.
Measured: Up to 62 weeks
Corticosteroid consumption
Corticosteroid consumption will be assessed at baseline and throughout treatment period. The mean corticosteroid dosage prior to study treatment will be considered as the patient's baseline. The changes in corticosteroids during treatment will be compared to baseline.
Measured: Up to 62 weeks
European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ-C30)
The changes in QoL during treatment will be compared to baseline. The highest scores reflect better overall health-related quality of life.
Measured: Up to 62 weeks
European Organization for Research and Treatment of Cancer (EORTC) brain cancer questionnaire (QLQ-BN20, assessment specific to brain neoplasm)
The changes in QoL during treatment will be compared to baseline. The highest scores reflect worse symptoms/problems.
Measured: Up to 62 weeks
Severity and frequency of treatment-related adverse events (AEs)
Documented and reported severity and frequency of AEs and/or SAEs will be assessed and classified based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Measured: Up to 62 weeks
Karnofsky performance status (KPS)
The KPS score is rated on a scale of 0 to 100, where 0 represents death, and 100 represents normalcy without complaints or evidence of disease. A higher score indicates the patient is better able to perform daily activities.
Measured: Up to 62 weeks
Mini-Mental State Examination (MMSE)
The MMSE is an 11-question measure that assesses multiple aspects of cognitive function. The maximum score is 30, with a higher score indicating less cognitive impairment.
Measured: Up to 62 weeks

Timeline

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

8 Nov 202431 Mar 2027

First posted11 Jul 2024
Study start8 Nov 2024
Primary completion31 Dec 2026 (estimated)
Study completion31 Mar 2027 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (6)Papers the sponsor has linked to this study.
Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind
Who is masked: Outcomes assessor
Enrolment: 32 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06496971
Sponsor's protocol ID: NF-2023-01
Status last verified: Apr 2026
First submitted: 1 Jul 2024
Last updated: 9 Apr 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

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
Liu HL, Hua MY, Chen PY, Chu PC, Pan CH, Yang HW, Huang CY, Wang JJ, Yen TC, Wei KC. Blood-brain barrier disruption with focused ultrasound enhances delivery of chemotherapeutic drugs for glioblastoma treatment. Radiology. 2010 May;255(2):415-25. doi: 10.1148/radiol.10090699.
PubMed 20413754
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.
PubMed 23527068
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
Chen KT, Lin YJ, Chai WY, Lin CJ, Chen PY, Huang CY, Kuo JS, Liu HL, Wei KC. Neuronavigation-guided focused ultrasound (NaviFUS) for transcranial blood-brain barrier opening in recurrent glioblastoma patients: clinical trial protocol. Ann Transl Med. 2020 Jun;8(11):673. doi: 10.21037/atm-20-344.
PubMed 32617293
Chen KT, Chai WY, Lin YJ, Lin CJ, Chen PY, Tsai HC, Huang CY, Kuo JS, Liu HL, Wei KC. Neuronavigation-guided focused ultrasound for transcranial blood-brain barrier opening and immunostimulation in brain tumors. Sci Adv. 2021 Feb 5;7(6):eabd0772. doi: 10.1126/sciadv.abd0772. Print 2021 Feb.
PubMed 33547073

Interested in taking part?

Sheang-Tze Fung, Ph.D.

02-25860560 ext. 167

stfung@navifus.com

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

Active, not recruitingPhase 3
EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma
Glioblastoma
RecruitingPhase 3
Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
Glioblastoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
Active, not recruitingPhase 1
Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma
Glioblastoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma

All Glioblastoma Multiforme trials

Study at a glance

From the registry record, last updated by the sponsor on 9 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Prospective, Randomized, Standard of Care Controlled, Parallel, Open-Label, Multicenter Pivotal Study to Evaluate the Efficacy and Safety of Avastin® in Combination With NaviFUS System Compared With Avastin® Alone for the Treatment of Recurrent Glioblastoma Multiforme (rGBM)
ClinicalTrials.gov ID: NCT06496971
Acronym / sponsor ID: NF-2023-01
Conditions: Glioblastoma Multiforme, Glioblastoma, Glioblastoma Multiforme, Adult, Glioma, Brain Tumor, Brain Tumor, Recurrent
Keywords: NaviFUS System, Blood-Brain Barrier Opening, Focused Ultrasound, FUS, Low-Intensity Focused Ultrasound, LIFU, Bevacizumab, BEV
Phase: Phase 3
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 32 participants (estimated)
Lead sponsor: NaviFUS CorporationIndustry (pharma, biotech, devices)
Study start: 8 Nov 2024 (actual)
Primary completion: 31 Dec 2026 (estimated)
Study completion: 31 Mar 2027 (estimated)
First posted: 11 Jul 2024 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Standard of care (SoC) BEV alone	Active comparator	Drug: BevacizumabSoC group will follow the standard operating procedures of BEV (10 mg/kg intravenous (IV) infusion over 30-90 minutes, following the instructions in the drug package insert).
Microbubble-mediated FUS treatment with BEV (FUS-MB+BEV)	Experimental	Drug: Bevacizumab, Drug: Microbubble, Device: Low-Intensity Focused UltrasoundFUS-MB+BEV group will follow the standard operating procedures of BEV (10 mg/kg intravenous (IV) infusion over 30-90 minutes, following the instructions in the drug package insert). After at least 30 minutes, patients will be administered microbubbles (MB) (SonoVue® ) at a dose of 0.1 mL/kg, along with optimal ultrasound exposure doses determined by the acoustic emission feedback FUS power control algorithm of the NaviFUS System.

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (31 listed)

Male or female patients ≥ 18 years of age at the time of study enrollment.
Body mass index (BMI) ≥ 17 kg/m2.
Patients diagnosed with glioblastoma must have unequivocal evidence of recurrence, as determined by contrast-enhanced magnetic resonance imaging (CE-MRI), following prior radiotherapy and temozolomide chemotherapy.
Patients may have undergone surgery for recurrence. The patients should have completed surgery and adequately recovered prior to the time of study enrollment.
Patients must have radiographic evidence of either at least an 80% resection of enhancing tumor following recurrence or a maximal measurable residual tumor ≤ 20 cm3.

Key exclusion criteria (27 listed)

Patients who have radiographic evidence of multifocal enhancing tumors.
Patients who have undergone previous treatment with anti-angiogenic therapy, including Bevacizumab, or other VEGF inhibitors or VEGF-receptor signaling inhibitors.
Patients who have previously received Carmustine wafers implantation during re-operation.
Patients who have previously received or are currently undergoing tumor treating fields (TTF) treatment.
Uncontrolled or significant cardiovascular disease, including any of the following:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BevacizumabAlso: AvastinAn anti-angiogenic agent to block tumor growth	Drug	Microbubble-mediated FUS treatment with BEV (FUS-MB+BEV), Standard of care (SoC) BEV alone
MicrobubbleAlso: SonoVueOpen the Blood-Brain Barrier (BBB) using focused ultrasound and microbubble	Drug	Microbubble-mediated FUS treatment with BEV (FUS-MB+BEV)
Low-Intensity Focused UltrasoundAlso: NaviFUS SystemOpen the Blood-Brain Barrier (BBB) using focused ultrasound and microbubble	Device	Microbubble-mediated FUS treatment with BEV (FUS-MB+BEV)

Primary outcome

6-month progression-free survival (PFS-6) of Bevacizumab (BEV) with or without microbubble-mediated focused ultrasound (FUS-MB) using NaviFUS System
Time frame: Up to 6 months
PFS-6 will be estimated the proportion of patients who remain progression-free at the 6-month time point, based on Response Assessment in Neuro-Oncology (RANO) Criteria, from the time of randomization.

13 secondary outcomes

12-month progression-free survival (PFS-12)
Time frame: Up to 12 months
Progression-free survival time (PFS)
Time frame: Up to 62 weeks
One- and Two-year survival rates
Time frame: Up to 12 and 24 months
Overall survival (OS)
Time frame: Up to 36 months
Objective response rate (ORR)
Time frame: Up to 62 weeks
Clinical benefit rate (CBR)
Time frame: Up to 62 weeks
Local disease control on the MRI Images
Time frame: Up to 62 weeks
Corticosteroid consumption
Time frame: Up to 62 weeks
European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ-C30)
Time frame: Up to 62 weeks
European Organization for Research and Treatment of Cancer (EORTC) brain cancer questionnaire (QLQ-BN20, assessment specific to brain neoplasm)
Time frame: Up to 62 weeks
Severity and frequency of treatment-related adverse events (AEs)
Time frame: Up to 62 weeks
Karnofsky performance status (KPS)
Time frame: Up to 62 weeks
Mini-Mental State Examination (MMSE)
Time frame: Up to 62 weeks

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2026.
Background: PubMed 41283685Chen 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.
Background: PubMed 20413754Liu HL, Hua MY, Chen PY, Chu PC, Pan CH, Yang HW, Huang CY, Wang JJ, Yen TC, Wei KC. Blood-brain barrier disruption with focused ultrasound enhances delivery of chemotherapeutic drugs for glioblastoma treatment. Radiology. 2010 May;255(2):415-25. doi: 10.1148/radiol.10090699.
Background: PubMed 23527068Wei 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.
Background: PubMed 27192459Liu 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.
Background: PubMed 32617293Chen KT, Lin YJ, Chai WY, Lin CJ, Chen PY, Huang CY, Kuo JS, Liu HL, Wei KC. Neuronavigation-guided focused ultrasound (NaviFUS) for transcranial blood-brain barrier opening in recurrent glioblastoma patients: clinical trial protocol. Ann Transl Med. 2020 Jun;8(11):673. doi: 10.21037/atm-20-344.
Background: PubMed 33547073Chen KT, Chai WY, Lin YJ, Lin CJ, Chen PY, Tsai HC, Huang CY, Kuo JS, Liu HL, Wei KC. Neuronavigation-guided focused ultrasound for transcranial blood-brain barrier opening and immunostimulation in brain tumors. Sci Adv. 2021 Feb 5;7(6):eabd0772. doi: 10.1126/sciadv.abd0772. Print 2021 Feb.
Related InfoLink provided by the sponsor.
Individual participant dataSharing planned: No

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Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma
Glioblastoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Sheang-Tze Fung, Ph.D. contact

02-25860560 ext. 167

stfung@navifus.com

Arthur Lung, Ph.D. contact

arthur.lung@navifus.com

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Bevacizumab, Microbubble and Low-Intensity Focused Ultrasound in people with Glioblastoma Multiforme and Glioblastoma, run by NaviFUS Corporation at 2 sites 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 31 inclusion and 27 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: looking for participants now, 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 2 sites 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.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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

Contact Sheang-Tze Fung, Ph.D. (02-25860560 ext. 167, stfung@navifus.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

6-month progression-free survival (PFS-6) of Bevacizumab (BEV) with or without microbubble-mediated focused ultrasound (FUS-MB) using NaviFUS System (time frame: Up to 6 months). 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 NCT06496971, 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.