A Pivotal Study to Evaluate the Safety and Effectiveness of Exablate Model 4000 Using Microbubble Resonators to Temporarily Mediate Blood-Brain Barrier Disruption (BBBD) in Subjects With Suspected Infiltrating Glioma
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 发起方
- InSightec
- 入组人数
- 120
- 试验地点
- 4
- 主要终点
- Overall safety of the Exablate BBBD procedure itself as measured through the collection of adverse events
研究概览
简要总结
The purpose of this study is to evaluate the safety and effectiveness of using the Exablate Type 2 system using microbubble resonators (Exablate Test Arm) to disrupt the Blood-Brain Barrier for the purpose of temporarily transforming, and thereby 'marking', regions of infiltrating gliomas prior to planned surgical resection, for the purpose of improving tumor visualization during the surgery to achieve a greater proportion of subjects who receive a Gross Total Resection (GTR) per plan compared to those not undergoing a BBBD procedure prior to resection (Control Arm).
详细描述
After being informed about the study and potential risks, all patients giving written informed consent will undergo screening to determine eligibility for study entry. Patients who meet the eligibility requirements will be randomized in a 2:1 ratio to Exablate Test Arm and to Control Arm, respectively. The following assessments will occur:
- Pre-surgical planning and Post-surgical visit MRI exams with and without contrast will be collected for evaluation by the study core lab; Any return to surgery for additional resection will be captured
- All subjects will be seen at ~Week 2, and ~4-Weeks post resection for physical and neurological exams and to assess for complications or adverse events. These visits should coincide with standard (Neuro-oncology) care following resection.
- Long-term outcomes will be collected during standard of care Neuro-oncology care follow-up visits for up to 2 years post resection; standard of care MRIs and RANO assessments will be collected.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Independent Reviewers (neurosurgeon/neuroradiologist), functioning as an Imaging Review Core Lab, will be blinded to the treatment assignment.
入排标准
- 年龄范围
- 21 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or Female between 21-85 years of age who are able and willing to give informed consent
- •Subjects with suspected Grade II, III or IV infiltrating glioma (IG) on pre-operative brain imaging scans who have a non-enhancing component and are planned for surgical resection.
- •Karnofsky Performance Score 70-100
- •Able to communicate sensations during the Exablate BBBD procedure
排除标准
- •Tumor originating from the deep midline, thalamus, midbrain, cerebellum or brainstem.
- •Multifocal tumors
- •MRI or clinical findings of:
- •Active or chronic infection(s) or inflammatory processes
- •Acute or chronic hemorrhages, specifically any lobar microbleeds, and no siderosis, amyloid angiopathy, or macro-hemorrhages
- •Intracranial thrombosis, vascular malformation, cerebral aneurysm or vasculitis
- •More than 30% of the skull area traversed by the sonication pathway is covered by scars, scalp disorders (e.g., eczema), or atrophy of the scalp
- •MR non-compatible metallic implants in the skull or the brain or the presence of unknown MR unsafe devices
- •Significant cardiac disease or unstable hemodynamic status
- •Documented myocardial infarction within six months of enrollment
- •Unstable angina on medication
- •Unstable or worsening congestive heart failure
- •Left ventricular ejection fraction below the lower limit of normal
- •History of a hemodynamically unstable cardiac arrhythmia
- •Cardiac pacemaker
- •Patient has right-to-left, bidirectional, or transient right-to-left cardiac shunts
- •Subjects with relative contraindications to perflutren including subjects with a family or personal history of QT prolongation or taking concomitant medications known to cause QTc prolongation,
- •Perflutren sensitivity or allergy ii. QT prolongation observed on screening ECG (QTc > 450 for men and >470 for women)
- •Uncontrolled hypertension (systolic > 180 and diastolic BP > 120 on medication)
- •Unable to discontinue use of anti-coagulant/antiplatelet therapy as per local standard.
- •History of a liver disease, bleeding disorder, coagulopathy or a history of spontaneous hemorrhage or evidence of increased risk of bleeding
- •Abnormal coagulation profile (Platelets < 80,000), PT (>14) or PTT (>36), and INR > 1.
- •Large lacunar lesions that cannot be navigated around
- •Known cerebral or systemic vasculopathy
- •Significant depression and at potential risk of suicide
- •Known sensitivity/allergy to gadolinium, or other intravascular contrast agents
- •Active seizures despite medication treatment (defined as >1 seizure per week) which could be worsened by disruption of the blood brain barrier
- •History of anaphylactic shock
- •Active drug or alcohol disorder which have a higher risk for seizures, infection and/or poor executive functioning
- •Positive HIV status, which can lead to increased entry of HIV into the brain parenchyma leading to HIV encephalitis
- •Potential blood-borne infections which can lead to increased entry to brain parenchyma leading to meningitis or brain abscess
- •Any contraindications to MRI scanning,
- •Impaired renal function with estimated glomerular filtration rate <30 mL/min/1.73m2
- •Severe Respiratory Illness
- •Currently in a clinical trial involving an investigational product or non-approved use of a drug or device
- •Pregnancy or Lactation
研究组 & 干预措施
Exablate Test Arm
Subjects will undergo ExAblate BBBD prior to their standard of care tumor removal
干预措施: Exablate BBBD (Device)
Control Test Arm
Subjects will undergo their standard of care tumor removal
结局指标
主要结局
Overall safety of the Exablate BBBD procedure itself as measured through the collection of adverse events
时间窗: Approximately 2 months
Safety of the Exablate BBBD procedure will be evaluated by patient examination and post-procedure MRI exams assessing changes in the treated region. Adverse events will be reported by the Investigator and monitored in both treatment arms.
Effectiveness of BBBD as determined by the proportion of subjects in whom a GTR is acheived
时间窗: MRI 72 hours post resection
The proportion of subjects in whom a gross total resection (actual versus planned) is achieved as measured on post-operative imaging compared to pre-resection imaging
次要结局
- Confirmation of accuracy of Exablate BBBD targeting(MRI immediately after the ExAblate procedure)
- Return Rate for Second Surgery for Completion of Resection(Approximately 2 months)