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

Recurrent Glioblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04988750
• Other study ID #: NF-2020-01
• Status: Recruiting
• Phase: N/A
• Start date: September 23, 2021
• Est. completion date: January 31, 2025

Study information

• Verified date: September 2023
• Source: NaviFUS Corporation
• Contact: Sheang-Tze Fung, Ph.D.
• Phone: +886(2) 25860560
• Email: stfung[@]navifus.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 8
• Est. completion date: January 31, 2025
• Est. primary completion date: October 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

1. Adult male/female patients = 20 years of age

2. Histologically proven glioblastoma multiforme (GBM) 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).

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.

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, 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); 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

Related Conditions & MeSH terms

• Glioblastoma
• Recurrent Glioblastoma

Intervention

Device:
• NaviFUS System
Using the neuronavigator to precisely guide the ultrasound energy to brain tissues in real-time and intraoperatively.

Locations

Country	Name	City	State
Taiwan	Chang Gung Medical Foundation	Taoyuan

Sponsors (1)

Lead Sponsor	Collaborator
NaviFUS Corporation

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Positron emission tomography (PET) uptake		Up to 6 months
Primary	Adverse events	Safety	up to 6 months
Secondary	Objective response rate (ORR)	ORR based on Response Assessment in Neuro-Oncology (RANO) criteria	Up to 6 months
Secondary	Progression-free survival (PFS)	PFS and median PFS based on RANO criteria	Up to 6 months
Secondary	Overall survival (OS)	OS and median OS	Up to 6 months
Secondary	Corticosteroid consumption	Compared the steroid dosage before treatment and after treatment	Up to 6 months
Secondary	Quality of life (QoL)		Up to 6 months