A Prospective, Open-Label, Single-Arm Pilot Study to Evaluate the Safety and Efficacy of Bevacizumab in Combination With NaviFUS System for the Treatment of Recurrent Glioblastoma Multiforme (rGBM)
Overview
- Phase
- Phase 1
- Intervention
- NaviFUS System
- Conditions
- Glioblastoma Multiforme
- Sponsor
- NaviFUS Corporation
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- Adverse Events (AEs)
- Status
- Recruiting
- Last Updated
- 23 days ago
Overview
Brief Summary
This will be a prospective, open-label, single-arm pilot study to investigate the safety and efficacy of Bevacizumab (BEV) in combination with microbubble (MB)-mediated FUS in patients with recurrent GBM. BEV represents the physician's best choice for the standard of care (SoC) in rGBM after previous treatment with surgery (if appropriate), standard radiotherapy with temozolomide chemotherapy, and with adjuvant temozolomide.
Detailed Description
The study aims to demonstrate the high safety profile and effectiveness of BEV+FUS-MB targeted therapy for brain tumors. Any patient with a histological diagnosis of GBM who meets all of the specific eligibility criteria may participate in this study by signing informed consent in person or through their legal representative. Eligible patients will undergo a 2-week baseline observation screening period. Up to 10 eligible patients will be enrolled in this study. Eligible patients will follow the standard operating procedures of BEV (10 mg/kg intravenous (IV) infusion). After at least 30 minutes, patients will be administered microbubbles (MB) (Lumason®) at a dose of 0.1 mL/kg, along with optimal ultrasound exposure doses determined by the acoustic emission feedback FUS power control algorithm of the NaviFUS System. The treatment will be administered every 2 weeks up to 34 weeks or until evidence of progression disease (PD), intolerable toxicity precluding further treatment, non-compliance with study follow-up, or withdrawal of consent, whichever occurs first.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female patients ≥ 18 years of age at the time of study enrollment.
- •Body mass index (BMI) ≥ 17 kg/m
- •Patients diagnosed with glioblastoma must have unequivocal evidence of recurrence, as determined by contrast-enhanced magnetic resonance imaging (CE-MRI), following prior radiotherapy and temozolomide chemotherapy.
- •Patients may have undergone surgery for recurrence. The patients should have completed surgery and adequately recovered prior to the time of study enrollment.
- •Patients must have radiographic evidence of either at least an 80% resection of enhancing tumor following recurrence or a maximal measurable residual tumor ≤ 20 cm
- •If patients are receiving corticosteroids, they must have been on a stable or decreasing dose of corticosteroids for at least 1 week prior to the planned first treatment.
- •At the time of study enrollment, the minimum interval since the last event:
- •4 weeks out from invasive procedures (e.g., open biopsy, surgical resection, significant traumatic injury, or any other major surgery involving entry into a body cavity) and the patient must have recovered from the effects of surgery
- •1 week out from minor surgical procedures or core biopsies
- •Patients must have recovered from the toxic effects of prior therapy at the time of study enrollment as follows:
Exclusion Criteria
- •Patients who have radiographic evidence of multifocal enhancing tumors.
- •Patients who have undergone previous treatment with anti-angiogenic therapy, including Bevacizumab, or other VEGF inhibitors or VEGF-receptor signaling inhibitors.
- •Patients who have previously received Carmustine wafers implantation during re-operation.
- •Patients who have previously received or are currently undergoing tumor treating fields (TTF) treatment.
- •Uncontrolled or significant cardiovascular disease, including any of the following:
- •New York Heart Association (NYHA) Grade II or above congestive heart failure (CHF) within 12 months prior to study enrollment
- •Unstable angina pectoris
- •Medical history of myocardial infarction within 6 months prior to study enrollment
- •Cardiac shunt
- •Stroke (except for transient ischemic attack; TIA) within 6 months prior to study enrollment
Arms & Interventions
FUS-MB+BEV
FUS treatment will be administered after BEV infusion to facilitate BBB opening.
Intervention: NaviFUS System
FUS-MB+BEV
FUS treatment will be administered after BEV infusion to facilitate BBB opening.
Intervention: Lumason
FUS-MB+BEV
FUS treatment will be administered after BEV infusion to facilitate BBB opening.
Intervention: Bevacizumab
Outcomes
Primary Outcomes
Adverse Events (AEs)
Time Frame: up to 52 weeks
The incidence and severity of AEs associated with FUS-MB+BEV treatment in patients with rGBM
Secondary Outcomes
- 6-month Progression-Free Survival (PFS-6)(up to 6 months)
- Progression-Free Survival (PFS)(up to 52 weeks)
- One-year Survival Rate(up to 12 months)
- Corticosteroid Consumption(up to 52 weeks)
- Local Disease Control on the MRI Images(up to 52 weeks)
- Objective Response Rate (ORR)(up to 52 weeks)
- Overall Survival (OS)(up to 24 months)
- Quality of life (QoL) assessment(up to 52 weeks)
- Clinical Benefit Rate (CBR)(up to 52 weeks)
- European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ-C30).(up to 52 weeks)
- European Organization for Research and Treatment of Cancer (EORTC) brain cancer questionnaire (QLQ-BN20, assessment specific to brain neoplasm)(Up to 52 weeks)