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

NCT04988750 | Completed

• 1 other identifier: NF-2020-01
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Recurrent Glioblastoma; High-Grade Glioma (WHO III-IV); Brain Tumor Adult; Brain Tumor, Recurrent; Brain Tumor, Adult: Glioblastoma

Keywords

NaviFUS System; Focused ultrasound; Low-intensity Focused Ultrasound; Radiosensitization

Outcome Measures

Primary Outcomes (1)

• Adverse events

  Safety

  up to 6 months

Secondary Outcomes (6)

• Objective response rate (ORR)

  Up to 6 months

• Progression-free survival (PFS)

  Up to 6 months

• Overall survival (OS)

  Up to 6 months

• Corticosteroid consumption

  Up to 6 months

• European Organization for Research and Treatment of Cancer (EORTC) Quality of life questionnaire (QLQ-C30)

  Up to 6 months

Other Outcomes (1)

• Positron emission tomography (PET) uptake

  Up to 6 months

Study Arms (1)

FUS + re-RT or FUS + SRS

EXPERIMENTAL

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

Interventions

NaviFUS System DEVICE

Using the neuronavigator to precisely guide the ultrasound energy to brain tissues in real-time and intraoperatively.

Also known as: Focused ultrasound, Low-Intensity Focused Ultrasound

FUS + re-RT or FUS + SRS

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 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.
• \. 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.
• \. 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.
• \. At the time of study treatment, 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 or inhibitor of VEGF or VEGFR (e.g., bevacizumab)
• weeks since the completion of a nitrosourea-containing chemotherapy regimen (e.g., carmustine \[BCNU\])
• \. Body mass index (BMI) ≥17 kg/ m2.
• \. Eastern Cooperative Oncology Group (ECOG) score ≤ 3.
• \. Patients with life expectancy ≥ 12 weeks.
• \. Adequate hepatic, renal, coagulation, and hematopoietic function.
• Hemoglobin ≥ 8 g/dL
• Platelets ≥ 100,000/mm3

You may not qualify if:

• Patients with implanted pacemaker, defibrillator or deep brain stimulator, other implanted electronic devices in the brain or documented clinically significant arrhythmias.
• 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.
• Patients with known HIV, however, that HIV testing is not required for entry into this study.
• Any patient requiring supplemental oxygen therapy.
• Use of any recreational drugs or history of drug addiction.
• Pregnant or breast-feeding women.
• The receipt of an investigational drug within a period of 28 days prior to the first FUS exposure.
• 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.
• 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 acute hemorrhage within the ROI.
• 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.
• Patients who have coagulopathy or risk factors for bleeding.
• Receiving anticoagulants or antiplatelet drugs within one week before study entry.
• Receiving medications known to increase the risk of bleeding within one month before study entry (e.g., bevacizumab).

Sponsors & Collaborators

• NaviFUS Corporation: lead

Study Sites (1)

Chang Gung Medical Foundation

Taoyuan District, 333, Taiwan

Location

Related Publications (2)

• 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.

  PMID: 33547073 BACKGROUND

• 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.

  PMID: 38598089 RESULT

MeSH Terms

Conditions

Glioblastoma; Glioma; Brain Neoplasms

Condition Hierarchy (Ancestors)

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

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: July 2, 2021
• First Posted: August 3, 2021
• Study Start: May 23, 2021
• Primary Completion: June 7, 2023
• Study Completion: June 16, 2025
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)