Evaluate the Safety and Preliminary Efficacy of the Combination of NaviFUS System With Re-irradiation for rGBM Patients

An Open Label, Prospective, Pilot Study to Evaluate the Safety and Preliminary Efficacy of the Combination of Focused Ultrasound With Re-irradiation for the Treatment Patients With Recurrent Glioblastoma Multiforme Using NaviFUS System

This is an open label, single arm, prospective, and pilot study. Eligible patients will be enrolled after acquiring the signed informed consent and then will receive the treatment of re-RT combined with FUS (FUS + re-RT) on an outpatient basis. The re-RT in FUS + re-RT treatment will include fractioned stereotactic radiosurgery (SRS) treatment (FUS + SRS) or conventional radiotherapy (cRT) treatment (FUS + cRT). The treatment of SRS or cRT treatment given to patients is determined by the investigator depending on the volume and location of the treatment region.

Study Overview

• Status: Completed
• Conditions: Recurrent Glioblastoma; Brain Tumor, Recurrent; Brain Tumor Adult; Brain Tumor, Adult: Glioblastoma; Brain Tumor Recurrent; High-Grade Glioma (WHO III-IV)
• Intervention / Treatment: Device: NaviFUS System

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taoyuan District, Taiwan, 333
    • Chang Gung Medical Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adult male/female patients ≥ 20 years of age.
2. Patients who meet one of the following criteria are considered eligible: (1) Histologically proven Grade IV glioma patients that is recurrent following standard radiation therapy (RT) and temozolomide and the second recurrent after prior treatment with an inhibitor of vascular endothelial growth factor (VEGF) or VEGFR (including bevacizumab) administration (bevacizumab failure).

(2) Histologically proven Grade III glioma patients that is recurrent following radiation therapy (RT) and/or temozolomide, who need re-RT treatment based on the physician's judgment.

3. Patients if already on the steroids then should be on a stable or decreasing dose of steroids for at least 7 days prior to study treatment.

4. Minimum interval since completion of radiation treatment is 12 weeks. The targeted region of the radiation treatment must be the same as the targeted region in the study according to the investigator's decision.

5. At the time of study treatment, minimum interval since last drug therapy:

1. 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)
2. 4 weeks since last cytotoxic therapy or inhibitor of VEGF or VEGFR (e.g., bevacizumab)
3. 6 weeks since the completion of a nitrosourea-containing chemotherapy regimen (e.g., carmustine [BCNU])

6. Body mass index (BMI) ≥17 kg/ m2.

7. Eastern Cooperative Oncology Group (ECOG) score ≤ 3.

8. Patients with life expectancy ≥ 12 weeks.

9. Adequate hepatic, renal, coagulation, and hematopoietic function.

1. Hemoglobin ≥ 8 g/dL
2. Platelets ≥ 100,000/mm3
3. Neutrophils ≥ 1,500/mm3
4. Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
5. Alanine transaminase (ALT) < 3 x ULN
6. Aspartate transaminase (AST) < 3 x ULN
7. Prothrombin time ≤ 1.2 x ULN
8. International Normalized Ratio (INR) < 1.5
9. Bilirubin < 2 x ULN

10. Patients with the region of interest (ROI) for FUS exposure are located at least 30 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.

11. Patients with the potential for pregnancy and their partner must agree to follow acceptable birth control methods to avoid conception. Female patients of child-bearing potential must have a negative pregnancy test.

12. Able to give written informed consent for the participation in the trial and comply with study requirements in the opinion of the investigator.

Exclusion Criteria:

1. Patients with implanted pacemaker, defibrillator or deep brain stimulator, other implanted electronic devices in the brain or documented clinically significant arrhythmias.
2. Patients with meningeal metastasis, intracranial stroke within the previous 6 months, congestive heart failure, unstable angina, cardiac arrhythmia, unstable cardiac status, and uncontrolled seizure activity.
3. Patients with known HIV, however, that HIV testing is not required for entry into this study.
4. Any patient requiring supplemental oxygen therapy.
5. Use of any recreational drugs or history of drug addiction.
6. Pregnant or breast-feeding women.
7. The receipt of an investigational drug within a period of 28 days prior to the first FUS exposure.
8. Known sensitivity/allergy to PET tracers, O-(2- [18F]fluoroethyl)- L-tyrosine (FET) or 2-Deoxy-2-[18F]fluoro-D-glucose (FDG); Magnetic Resonance Imaging (MRI) contrast agents, Dotarem; Computer Tomography (CT) contrast agents; SonoVue®; or any of its components.
9. 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.
10. Abnormal baseline findings considered by the investigator to indicate conditions that might affect study endpoints.
11. Patients who have acute hemorrhage within the ROI.
12. Major surgery or significant traumatic injury that has not been recovered from by 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.
13. Patients who have coagulopathy or risk factors for bleeding.
14. Receiving anticoagulants or antiplatelet drugs within one week before study entry.
15. Receiving medications known to increase the risk of bleeding within one month before study entry (e.g., bevacizumab).
16. Contraindications to MRI, including but not limited to metallic implants and claustrophobia.
17. Patients with severe hypertension (defined as systolic blood pressure > 180 mmHg or diastolic blood pressure >100 mmHg).
18. Patients with cardiac shunt.
19. Patients with anticancer therapy-related adverse events which are unrecovered/unresolved to baseline or at grade 1 in severity.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: FUS + re-RT or FUS + SRS; The SRS treatment will be administered for 3 consecutive days (one fraction of 7-9 Gy per day; total dose 21-27 Gy), including SRS treatment 1 (SRS 1), SRS treatment 2 (SRS 2), and SRS treatment 3 (SRS 3). At the SRS 1 and SRS 3, the patients will be shaved their hair at first, and the patient registration will be performed for the neuronavigation system according to the instruction of the system. cRT will be administered for 5 consecutive days within one week, and a full course is two weeks (one fraction of 3-4 Gy per day; total dose: 30-40 Gy), including cRT treatment 1 to cRT treatment 10 (cRT 1-cRT 10). At the cRT 1, cRT 3, cRT 6, and cRT 8, the patients will be shaved their hair at first, and the patient registration will be performed for the neuronavigation system according to the instruction of the system.

Device: NaviFUS System; Using the neuronavigator to precisely guide the ultrasound energy to brain tissues in real-time and intraoperatively.; Other Names: Focused ultrasound; Low-Intensity Focused Ultrasound

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Safety	up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	ORR based on Response Assessment in Neuro-Oncology (RANO) criteria	Up to 6 months
Progression-free survival (PFS)	PFS and median PFS based on RANO criteria	Up to 6 months
Overall survival (OS)	OS and median OS	Up to 6 months
Corticosteroid consumption	Compared the steroid dosage before treatment and after treatment	Up to 6 months
European Organization for Research and Treatment of Cancer (EORTC) Quality of life questionnaire (QLQ-C30)	Compared the Quality of Life before treatment and after treatment. The higher summary scores reflect better overall health-related quality of life.	Up to 6 months
European Organization for Research and Treatment of Cancer (EORTC) Brain Cancer questionnaire (BN20)	Compared the Quality of Life before treatment and after treatment. The higher summary scores reflect worse symptoms/problems.	Up to 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positron emission tomography (PET) uptake	to assess the treatment response (treatment-related changes from true progression and radiation necrosis)	Up to 6 months

Collaborators and Investigators

• Sponsor: NaviFUS Corporation

Publications and helpful links

General Publications

• 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.
• Chen KT, Huang CY, Pai PC, Yang WC, Tseng CK, Tsai HC, Li JC, Chuang CC, Hsu PW, Lee CC, Toh CH, Liu HL, Wei KC. Correction to: Focused ultrasound combined with radiotherapy for malignant brain tumor: a preclinical and clinical study. J Neurooncol. 2024 Apr;167(2):371. doi: 10.1007/s11060-024-04671-w. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2021
• Primary Completion (Actual): June 7, 2023
• Study Completion (Actual): June 16, 2025

Study Registration Dates

• First Submitted: July 2, 2021
• First Submitted That Met QC Criteria: July 26, 2021
• First Posted (Actual): August 3, 2021

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Radiosensitization; Focused ultrasound; NaviFUS System; Low-intensity Focused Ultrasound
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Central Nervous System Neoplasms; Glioblastoma; Glioma; Brain Neoplasms
• Other Study ID Numbers: NF-2020-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No