Combining NaviFUS System with Re-irradiation for Recurrent Glioblastoma 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 study is testing if a new treatment using the NaviFUS System combined with re-radiation can help adults with recurring glioblastoma feel better and improve their condition.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 8 (estimated)
• Ages: 20 Years and up
• Sex: All
• Sponsor: NaviFUS Corporation (industry)
• Drugs / interventions: bevacizumab, chemotherapy, radiation, cytoxan
• Locations: 1 site (Taoyuan)
• Trial ID: NCT04988750 on ClinicalTrials.gov

What this trial studies

This open-label, single-arm pilot study aims to evaluate the safety and preliminary efficacy of the NaviFUS System in combination with re-irradiation for patients with recurrent glioblastoma multiforme. Eligible participants will receive either fractioned stereotactic radiosurgery or conventional radiotherapy alongside the NaviFUS treatment, based on the investigator's assessment of the tumor's volume and location. The study will enroll adult patients who have experienced recurrence after standard treatments, ensuring they meet specific criteria regarding prior therapies and steroid use.

Who should consider this trial

Good fit: Ideal candidates are adults aged 20 and older with histologically confirmed recurrent glioblastoma following standard therapies.

Not a fit: Patients who have not experienced recurrence after standard treatment or those with contraindications to the proposed therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new treatment option for patients with recurrent glioblastoma, potentially improving their outcomes.

How similar studies have performed: While the combination of re-irradiation and focused ultrasound is a novel approach, similar studies have shown promise in treating other types of tumors, indicating potential for success.

Eligibility criteria

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

Where this trial is running

Taoyuan

• Chang Gung Medical Foundation — Taoyuan, Taiwan (RECRUITING)

Study contacts

• Study coordinator: Sheang-Tze Fung, Ph.D.

Conditions: Recurrent Glioblastoma