Clinical Trials /

Blood Brain Barrier Disruption (BBBD) Using MRgFUS in the Treatment of Her2-positive Breast Cancer Brain Metastases

NCT03714243

Description:

The purpose of this study is to evaluate the safety of BBB disruption using the ExAblate 4000-system Type 2 in patients with Her-2 positive breast cancer metastases in the brain.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Blood Brain Barrier Disruption (BBBD) Using MRgFUS in the Treatment of Her2-positive Breast Cancer Brain Metastases
  • Official Title: A Study to Evaluate the Safety and Feasibility of Blood-Brain Barrier Disruption Using MRI-Guided Focused Ultrasound in the Treatment of Her2-positive Breast Cancer Brain Metastases

Clinical Trial IDs

  • ORG STUDY ID: BT006
  • SECONDARY ID: 277990
  • NCT ID: NCT03714243

Conditions

  • Breast Cancer
  • Brain Metastases

Purpose

The purpose of this study is to evaluate the safety of BBB disruption using the ExAblate 4000-system Type 2 in patients with Her-2 positive breast cancer metastases in the brain.

Detailed Description

      The goal of this prospective, single arm, non-randomized study is to evaluate the safety and
      feasibility of using the ExAblate Model 4000 Type 2 "Neuro-System" as a tool to disrupt the
      blood brain barrier in a temporary and localized fashion in patients with breast cancer and
      brain metastases. Up to 10 patients will be recruited at Sunnybrook. Patients will be
      consented, screened, and undergo study treatment. Follow up will continue through 12 weeks
      post treatment and then subject's participation in the study will be complete. Data will be
      collected to establish the basic safety of this type of treatment as the basis for later
      studies to evaluate clinical efficacy.
    

Trial Arms

NameTypeDescriptionInterventions
ExAblate BBBDExperimentalUsing ExAblate Model 4000 Type-2 to temporarily disrupt the blood brain barrier in patients with Her-2 positive breast cancer and brain metastases

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Men and women between 18 and 80 years of age
    
              -  Able and willing to give informed consent
    
              -  Metastatic Her2-positive breast cancer with brain metastases
    
              -  Karnofsky performance score 70-100
    
              -  ASA score 1-3
    
              -  Able to communicate sensations during the ExAblate BBBD procedure
    
              -  Able to attend all study visits (i.e., life expectancy of at least 3 months)
    
              -  At least 14 days passed since last brain surgery
    
              -  At least 6 weeks passed since last radiation treatment
    
              -  Any previous systemic treatments are allowed, but a time interval of 1-3 weeks should
                 have passed since the last treatment
    
            Exclusion Criteria:
    
              -  Brain metastases not visible on the pre-therapy imaging
    
              -  The sonication pathway to the tumour involves:
    
                 i. Extensive scalp scars ii. Clips or other metallic implanted objects in the skull or
                 the brain, except shunts
    
              -  The subject presents with symptoms and signs of increased intracranial pressure (e.g.,
                 headache, nausea, vomiting, lethargy, and papilledema)
    
              -  Cardiac disease or unstable hemodynamics including:
    
                 i. Documented myocardial infarction within six months of enrolment ii. Unstable angina
                 on medication iii. Congestive heart failure iv. Left ventricular ejection fraction <
                 50% v. Right-to-left, bidirectional, or transient right-to-left cardiac shunts vi.
                 History of a hemodynamically unstable cardiac arrythmia vii. Cardiac pacemaker viii.
                 Contraindications to perflutren including subjects with a family or personal history
                 of QT prolongation or taking concomitant medications known to cause QTc prolongation
    
              -  Severe hypertension (diastolic BP > 100 on medication)
    
              -  Anti-coagulant therapy or medications known to increase risk of hemorrhage within
                 washout period prior to treatment (i.e. antiplatelet or vitamin K inhibitor
                 anticoagulants within 7 days, non-vitamin K inhibitor anticoagulants within 72 hours,
                 or heparin-derived compounds within 48 hours of treatment)
    
              -  History of a bleeding disorder, coagulopathy or with a history of spontaneous tumour
                 hemorrhage
    
              -  Abnormal level of platelets (< 100000) or INR > 1.3
    
              -  Documented cerebral infarction within the past 12 months
    
              -  Transient Ischemic Attack (TIA) in the last 1 month
    
              -  Insulin-dependent diabetes mellitus
    
              -  Known allergy sensitivity or contraindications to gadolinium-diethylenetriamine
                 penta-acetic acid (DTPA), CT contrast, or perflutren
    
              -  Allergy to eggs or egg products
    
              -  Contraindications to MRI such as non-MRI-compatible implanted devices
    
              -  Large subjects not fitting comfortably into the MRI scanner (generally >250 lbs)
    
              -  Difficulty lying supine and still for up to 4 hours in the MRI unit or claustrophobia
    
              -  Untreated, uncontrolled sleep apnea
    
              -  Positive pregnancy test (for pre-menopausal women)
    
              -  Known life-threatening systemic disease
    
              -  Severely impaired renal function
    
              -  Respiratory: chronic pulmonary disorders, e.g. severe emphysema, chronic obstructive
                 pulmonary disease (COPD), pulmonary vasculitis, or other causes of reduced pulmonary
                 vascular cross-sectional area, subjects with a history of drug allergies
    
              -  Any illness or medical condition that in the investigator's opinion precludes
                 participation in this study
          
    Maximum Eligible Age:80 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Adverse events
    Time Frame:Throughout the study, approximately 3 months.
    Safety Issue:
    Description:Rate of adverse events following each treatment through end of study

    Secondary Outcome Measures

    Measure:Feasibility of BBBD
    Time Frame:Immediately after each BBBD procedure
    Safety Issue:
    Description:The extent of BBB opening will be determined by the degree of contrast enhancement seen on post-procedure MRI with contrast agent

    Details

    Phase:N/A
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:InSightec

    Last Updated