Trial Title:
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 ID:
NCT06496971
Condition:
Glioblastoma Multiforme
Glioblastoma
Glioblastoma Multiforme, Adult
Glioma
Brain Tumor
Brain Tumor, Recurrent
Neoplasms
Neoplasms, Nerve Tissue
Conditions: Official terms:
Neoplasms
Glioblastoma
Brain Neoplasms
Neoplasms, Nerve Tissue
Recurrence
Bevacizumab
Conditions: Keywords:
NaviFUS System
Blood-Brain Barrier Opening
Focused Ultrasound
FUS
Low-Intensity Focused Ultrasound
LIFU
Bevacizumab
BEV
Avastin
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Single (Outcomes Assessor)
Masking description:
Evaluators for radiological response assessment will be blinded to the patient's assigned
treatment.
Intervention:
Intervention type:
Drug
Intervention name:
Bevacizumab
Description:
An anti-angiogenic agent to block tumor growth
Arm group label:
Microbubble-mediated FUS treatment with BEV (FUS-MB+BEV)
Arm group label:
Standard of care (SoC) BEV alone
Other name:
Avastin
Intervention type:
Drug
Intervention name:
Microbubble
Description:
Open the Blood-Brain Barrier (BBB) using focused ultrasound and microbubble
Arm group label:
Microbubble-mediated FUS treatment with BEV (FUS-MB+BEV)
Other name:
SonoVue
Intervention type:
Device
Intervention name:
Low-Intensity Focused Ultrasound
Description:
Open the Blood-Brain Barrier (BBB) using focused ultrasound and microbubble
Arm group label:
Microbubble-mediated FUS treatment with BEV (FUS-MB+BEV)
Other name:
NaviFUS System
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.
Detailed description:
The study aims to compare the efficacy of combining Bevacizumab with NaviFUS System
relative to Bevacizumab alone in patients with rGBM who have previously undergone
radiotherapy and temozolomide chemotherapy.
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 32 evaluable patients will be recruited in this study. Eligible patients will be
randomized in a 1:1 ratio, with one group receiving the standard of care (SoC) BEV alone
and the other group receiving treatment with microbubble-mediated FUS treatment in
addition to BEV (FUS-MB+BEV).
Eligible patients who assigned to the SoC group will follow the standard operating
procedures of BEV (10 mg/kg intravenous (IV) infusion over 30-90 minutes). On the other
hand, eligible patients assigned to treatment group will initially receive the same BEV
schedule. After at least 30 minutes, patients will be administered microbubbles (MB)
(SonoVue® ) 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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Male or female patients ≥ 18 years of age at the time of study enrollment.
2. Body mass index (BMI) ≥ 17 kg/m2.
3. 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.
4. Patients may have undergone surgery for recurrence. The patients should have
completed surgery and adequately recovered prior to the time of study enrollment.
5. Patients must have radiographic evidence of either at least an 80% resection of
enhancing tumor following recurrence or a maximal measurable residual tumor ≤ 20
cm3.
6. 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.
7. 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
8. Patients must have recovered from the toxic effects of prior therapy at the time of
study enrollment as follows:
- 4 weeks out from any investigational drug or device
- 4 weeks out from chemotherapy
- 6 weeks since the completion of a nitrosourea-containing chemotherapy regimen
(e.g., Carmustine (BCNU))
- 12 weeks out from completion of radiotherapy
9. Patients should have a life expectancy ≥ 12 weeks.
10. Patients must have Karnofsky Performance Status (KPS) ≥ 70.
11. Adequate hematopoietic, renal, hepatic, and coagulation function, defined as:
- Hemoglobin ≥ 10 g/dL
- Platelets ≥ 100,000/mm3
- Neutrophils ≥ 1,500/mm3
- Serum creatinine ≤ 1.5 × upper limit of normal (ULN)
- Urine protein creatinine ratio (UPCR) < 1 or urine dipstick for proteinuria ≤
2+
- Alanine aminotransferase (ALT) < 3 × ULN
- Aspartate aminotransferase (AST) < 3 × ULN
- Total bilirubin (TBL) < 2 × ULN
- Prothrombin time ≤ 1.5 x ULN
- International Normalized Ratio (INR) < 1.5 These tests must be conducted within
2 weeks prior to the planned first treatment.
12. The central of FUS exposure region is located with a minimum distance of at least 30
mm beneath the skull bone.
13. Females of childbearing potential must have a negative pregnancy test documented
within 2 weeks prior to first treatment. Females of childbearing potential and male
patients with partners of childbearing potential must agree to adhere to an
acceptable method of contraception (as outlined below) from prior to the first study
treatment until at least 6 months after the completion of last treatment. Standard
acceptable methods of contraception include the use of highly effective methods such
as hormonal contraception, diaphragm, cervical cap, vaginal sponge, condom,
spermicide, vasectomy, intrauterine device, or abstinence from sexual activity.
14. Patients are able and willing to have peripheral intravenous (IV) line placement of
Bevacizumab and are able to have hair shaved (either whole head or in the region
where the coupling membrane will touch) prior to FUS treatment if assigned to
treatment group.
15. Patients or their legal representatives are able to provide written informed consent
for participation in the trial and patients are willing to comply the procedures
(i.e., study-related assessments), instructions, and restrictions outlined in this
study in the duration of the study. Informed consent should also be given for
biological materials and diagnostic imaging to be stored and used for future
research on brain tumors.
Exclusion Criteria:
1. Patients who have radiographic evidence of multifocal enhancing tumors.
2. Patients who have undergone previous treatment with anti-angiogenic therapy,
including Bevacizumab, or other VEGF inhibitors or VEGF-receptor signaling
inhibitors.
3. Patients who have previously received Carmustine wafers implantation during
re-operation.
4. Patients who have previously received or are currently undergoing tumor treating
fields (TTF) treatment.
5. 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
6. Stroke (except for transient ischemic attack; TIA) within 6 months prior to study
enrollment.
7. Patients with implanted electronic device, for example, implanted
cardioverter-defibrillator (ICD), cardiac pacemaker, permanent medication pumps,
cochlear implants, responsive neurostimulator (RNS), deep brain stimulation (DBS),
or other electronic devices implanted in the brain. Patients with contraindications
for MRI as judged by Investigator, including non-MRI compatible metallic implant(s).
8. Patients with inadequately controlled hypertension, defined as systolic blood
pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg while on medication,
within 2 weeks prior to first treatment.
9. Patients with evidence of any thrombotic or hemorrhagic events, including but not
limited to:
- Inherited bleeding diathesis or significant coagulopathy with the risk of
bleeding (i.e., in the absence of therapeutic anticoagulation).
- History of pulmonary haemorrhage/haemoptysis ≥ grade 2 according to the CTCAE
version 5.0 criteria within 1 month prior to study enrollment
- Arterial or venous thrombosis (e.g., pulmonary embolism) within 3 months prior
to study enrollment
10. Patients with unstable pulmonary disease or chronic obstructive pulmonary disease
(COPD) exacerbation or other respiratory illness requiring hospitalization or
precluding study therapy at the time of study enrollment.
11. Patients who have psychiatric illness/social situations that would limit compliance
with study requirements.
12. Know HIV-positive patient, however, that HIV testing is not required for entry into
this study.
13. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of
study enrollment.
14. History or evidence of active gastroduodenal ulcer, gastrointestinal
perforations/fistula, or intra-abdominal abscess within 6 months prior to study
enrollment.
15. Receiving anticoagulant (e.g., warfarin or LMW heparin) or antiplatelet (e.g.,
aspirin) therapy within 1 week prior to beginning treatment.
16. Known sensitivity/allergy to Magnetic Resonance Imaging (MRI) contrast agents,
Computer Tomography (CT) contrast agents, SonoVue®, Bevacizumab, or any of their
components.
17. Pregnant (positive pregnancy test) or breast-feeding women.
18. Use of any recreational drugs or history of drug addiction.
19. Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g.,
active or uncontrolled infection, uncontrolled epilepsy, uncontrolled diabetes) that
could cause unacceptable safety risks or compromise compliance with the protocol.
20. Any other condition that, in the Investigator's discretion, might increase the risk
to the patients or compromise the evaluation of the clinical trial endpoints.
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
National Taiwan University Hospital
Address:
City:
Taipei
Zip:
10048
Country:
Taiwan
Contact:
Last name:
Dar-Ming Lai, M.D., Ph.D.
Email:
dmlai@ntu.edu.tw
Facility:
Name:
Linkou Chang Gung Memorial Hospital
Address:
City:
Taoyuan
Zip:
33305
Country:
Taiwan
Contact:
Last name:
Kuo-Chen Wei, M.D.
Email:
kuochenwei@cgmh.org.tw
Start date:
September 1, 2024
Completion date:
March 31, 2027
Lead sponsor:
Agency:
NaviFUS Corporation
Agency class:
Industry
Source:
NaviFUS Corporation
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06496971
http://classic.clinicaltrials.gov/ct2/show/NCT04446416
