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
NCT Number: NCT06496971
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Glioblastoma Multiforme|Glioblastoma|Glioblastoma Multiforme, Adult|Glioma|Brain Tumor|Brain Tumor, Recurrent|Neoplasms|Neoplasms, Nerve Tissue
Interventions: DRUG: Bevacizumab|DRUG: Microbubble|DEVICE: Low-Intensity Focused Ultrasound
Sponsor: NaviFUS Corporation
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 32
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: SINGLE (OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-09-01
Completion Date: 2027-03-31
Locations: National Taiwan University Hospital, Taipei, 10048, Taiwan|Linkou Chang Gung Memorial Hospital, Taoyuan, 33305, Taiwan

Summary:
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.

Primary Outcome Measures: 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., Up to 6 months
Secondary Outcome Measures: 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., 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., 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., 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., 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., 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., 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., 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., 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., 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., 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., Up to 62 weeks