<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04431674</url>
  </required_header>
  <id_info>
    <org_study_id>077-2019</org_study_id>
    <nct_id>NCT04431674</nct_id>
  </id_info>
  <brief_title>Novel MRI-Guided Ultrasound Stimulated Microbubble Radiation Treatment for Patients With Chest-wall and Locally-Advanced Breast Cancer</brief_title>
  <acronym>USmBRT-B</acronym>
  <official_title>Novel MRI-Guided Ultrasound Stimulated Microbubble Radiation Treatment for Patients With Chest-wall and Locally-Advanced Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sunnybrook Health Sciences Centre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sunnybrook Health Sciences Centre</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this study is to demonstrate the feasibility of novel MRI-guided ultrasound&#xD;
      stimulated microbubble treatment to enhance radiation effects in humans receiving external&#xD;
      beam radiotherapy delivered using a LINAC (linear accelerator) radiation therapy device.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The objective of this study is to demonstrate the feasibility of novel MRI-guided ultrasound&#xD;
      stimulated microbubble treatment to enhance radiation effects in humans receiving external&#xD;
      beam radiotherapy delivered using a LINAC (linear accelerator) radiation therapy device. The&#xD;
      investigators have previously demonstrated that ultrasound and microbubble mediated&#xD;
      endothelial cell perturbation can significantly enhance the effectiveness of radiation. It&#xD;
      enhances tumour response to radiation significantly by synergistically destroying tumour&#xD;
      blood vessels. The technique is targeted spatially and achieves tumour specificity by&#xD;
      confining the low-power ultrasonic fields that stimulate microbubbles to the tumour location&#xD;
      only. By perturbing the tumour vasculature and activating specific genetic pathways, the&#xD;
      technique sensitizes the targeted tissues to the subsequent therapeutic application of&#xD;
      radiation, resulting in significantly enhanced cell killing. The primary aim of this research&#xD;
      is to evaluate the safety profile of MRI-guided ultrasound stimulated microbubble treatment&#xD;
      and radiation in patients with chest wall and breast cancer. The secondary aim is to evaluate&#xD;
      tumor (primary and/or nodal) response to MRg-FU + MB and radiation, as measured&#xD;
      radiologically within the treated therapeutic regions.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 31, 2020</start_date>
  <completion_date type="Anticipated">June 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2024</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Prospective, Single-Centre, Single-Arm, Non-Randomized, Phase-I MRI-Guided Ultrasound Stimulated Microbubbles Radiation Treatment for Patients with Chest Wall and Breast Cancer</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of toxicity and adverse events using MRg-FUS+MB treatment in patients with chest-wall and locally advanced breast cancer</measure>
    <time_frame>90 days</time_frame>
    <description>Incidence of toxicity and adverse events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Radiological Response</measure>
    <time_frame>90 days</time_frame>
    <description>The secondary endpoint is radiological response in breast cancer following MRg-FU + MB + radiation, after a 3 month follow up.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>MRg-FUS MB Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with locally advanced breast cancer (LABC) and chest wall tumours will receive MRI-guided ultrasound-stimulated microbubble-treatment combined with radiotherapy on a LINAC.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Definity Suspension for Injection</intervention_name>
    <description>MRI-guided ultrasound-stimulated microbubble-treatment</description>
    <arm_group_label>MRg-FUS MB Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  All biopsy-confirmed invasive ductal, invasive lobular and other rare histologic types&#xD;
             of carcinoma within past three months&#xD;
&#xD;
          -  Patients with early stage Breast cancer, or LABC ; i.e., Stage IIA - IIIC cancers (T2&#xD;
             N0 M0 to Any T, N3, M0) or Stage IV (Any T, Any N, M1) per AJCC guidelines (8th&#xD;
             Edition)&#xD;
&#xD;
          -  Assessed by a multidisciplinary team of treating medical, surgical and radiation&#xD;
             oncologist and found suitable for the treatment&#xD;
&#xD;
          -  Patient referred for standard radiotherapy, which may include any of the following&#xD;
             dose regimens: 1) 20 Gy in 5 fractions, 2) 30 Gy in 10 fractions, 3) 40 Gy in 10&#xD;
             fractions, 4) 50 Gy in 20 fractions, 5) 60 Gy in 30 fractions and 6) 66 Gy in 33&#xD;
             fractions.&#xD;
&#xD;
          -  Able to understand and give informed consent&#xD;
&#xD;
          -  Weight &lt; 140 kg&#xD;
&#xD;
          -  Target lesion accessible for MRg-FU+MB procedure&#xD;
&#xD;
          -  Able to communicate sensation during the procedure&#xD;
&#xD;
          -  Patient with normal coagulation profile, CBC, liver profile (bilirubin/ ALT/ALP),&#xD;
             electrolytes (sodium, potassium, chloride, CO2 total), BUN and creatinine.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or lactating women may not participate due to the embryotoxic effects of&#xD;
             protocol treatment. Women/ men of reproductive potential may not participate unless&#xD;
             they have agreed to use an effective contraceptive method.&#xD;
&#xD;
          -  Unable to have a contrast-enhanced MRI scan - standard of care criteria&#xD;
&#xD;
          -  Patients on anthracycline or taxane based chemotherapy&#xD;
&#xD;
          -  Patients with metallic or breast implants&#xD;
&#xD;
          -  Subjects with inflammatory breast cancer, connective tissue disorder, musculoskeletal&#xD;
             deformity&#xD;
&#xD;
          -  Target lesion causing ulceration, bleeding or discharge of the overlying skin&#xD;
&#xD;
          -  A fibrotic scar along the proposed FU beam path&#xD;
&#xD;
          -  Severe cardiovascular, neurological, renal or hematological chronic disease&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status ≥ 3&#xD;
&#xD;
          -  Any condition in the investigator's opinion precludes participation&#xD;
&#xD;
          -  Bleeding disorders/ High risk for deep vein thrombosis&#xD;
&#xD;
          -  Unable to tolerate required stationary position during treatment&#xD;
&#xD;
          -  Allergic to Definity microbubbles&#xD;
&#xD;
          -  Cardiac disease or unstable hemodynamics including myocardial infarction within six&#xD;
             months, unstable angina, congestive heart failure, ejection fraction &lt; 50%, cardiac&#xD;
             shunts, cardiac arrythmia and cardiac pacemaker.&#xD;
&#xD;
          -  Contraindication to perflutren including subjects with a family or personal history of&#xD;
             QT prolongation or taking concomitant medications known to cause QTc prolongation like&#xD;
             cisapride, erythromycin, tricyclic antidepressants, Class IA and III antiarrhythmic&#xD;
             agents and some antipsychotics like haloperidol, droperidol, quetiapine, thioridazine,&#xD;
             ziprasidone.&#xD;
&#xD;
          -  QT prolongation observed on screening ECG (QTc &gt; 450ms for men or &gt;470ms for women)&#xD;
&#xD;
          -  Severe hypertension (diastolic BP &gt; 100 mmHg)&#xD;
&#xD;
          -  Patients concurrently taking anti-coagulant therapy like antiplatelets or vitamin K&#xD;
             inhibitors or heparin derivatives&#xD;
&#xD;
          -  History of bleeding disorder, coagulopathy&#xD;
&#xD;
          -  Severely impaired renal function with estimated glomerular filtration rate &lt;&#xD;
             30ml/min/1.73m2 and/or on dialysis&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dr. Gregory Czarnota, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sunnybrook Health Sciences Centre</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Dr. Gregory Czarnota, MD</last_name>
    <phone>+1 (416) 480-6128</phone>
    <phone_ext>7073</phone_ext>
    <email>Gregory.Czarnota@sunnybrook.ca</email>
  </overall_contact>
  <location>
    <facility>
      <name>Sunnybrook Health Sciences Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4N 3M5</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gregory J Czarnota, PhD, MD</last_name>
      <phone>(416) 480-6128</phone>
      <email>gerogory.czarnota@sunnybrook.ca</email>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>June 11, 2020</study_first_submitted>
  <study_first_submitted_qc>June 11, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>July 11, 2022</last_update_submitted>
  <last_update_submitted_qc>July 11, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 13, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sunnybrook Health Sciences Centre</investigator_affiliation>
    <investigator_full_name>Dr. Gregory Czarnota</investigator_full_name>
    <investigator_title>Senior Scientist, MD</investigator_title>
  </responsible_party>
  <keyword>Breast Cancer</keyword>
  <keyword>Focused ultrasound</keyword>
  <keyword>Microbubbles</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04431674
org study id: 077-2019
nct id: NCT04431674
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: Yes
The objective of this study is to demonstrate the feasibility of novel MRI-guided ultrasound
      stimulated microbubble treatment to enhance radiation effects in humans receiving external
      beam radiotherapy delivered using a LINAC (linear accelerator) radiation therapy device.
The objective of this study is to demonstrate the feasibility of novel MRI-guided ultrasound
      stimulated microbubble treatment to enhance radiation effects in humans receiving external
      beam radiotherapy delivered using a LINAC (linear accelerator) radiation therapy device. The
      investigators have previously demonstrated that ultrasound and microbubble mediated
      endothelial cell perturbation can significantly enhance the effectiveness of radiation. It
      enhances tumour response to radiation significantly by synergistically destroying tumour
      blood vessels. The technique is targeted spatially and achieves tumour specificity by
      confining the low-power ultrasonic fields that stimulate microbubbles to the tumour location
      only. By perturbing the tumour vasculature and activating specific genetic pathways, the
      technique sensitizes the targeted tissues to the subsequent therapeutic application of
      radiation, resulting in significantly enhanced cell killing. The primary aim of this research
      is to evaluate the safety profile of MRI-guided ultrasound stimulated microbubble treatment
      and radiation in patients with chest wall and breast cancer. The secondary aim is to evaluate
      tumor (primary and/or nodal) response to MRg-FU + MB and radiation, as measured
      radiologically within the treated therapeutic regions.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Prospective, Single-Centre, Single-Arm, Non-Randomized, Phase-I MRI-Guided Ultrasound Stimulated Microbubbles Radiation Treatment for Patients with Chest Wall and Breast Cancer
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of toxicity and adverse events using MRg-FUS+MB treatment in patients with chest-wall and locally advanced breast cancer
time frame: 90 days
description: Incidence of toxicity and adverse events
measure: Radiological Response
time frame: 90 days
description: The secondary endpoint is radiological response in breast cancer following MRg-FU + MB + radiation, after a 3 month follow up.
arm group label: MRg-FUS MB Treatment
arm group type: Experimental
description: Patients with locally advanced breast cancer (LABC) and chest wall tumours will receive MRI-guided ultrasound-stimulated microbubble-treatment combined with radiotherapy on a LINAC.
intervention type: Drug
intervention name: Definity Suspension for Injection
description: MRI-guided ultrasound-stimulated microbubble-treatment
arm group label: MRg-FUS MB Treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dr. Gregory Czarnota, MD
role: Principal Investigator
affiliation: Sunnybrook Health Sciences Centre
last name: Dr. Gregory Czarnota, MD
phone: +1 (416) 480-6128
phone ext: 7073
email: Gregory.Czarnota@sunnybrook.ca
facility: 
status: Recruiting
contact: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: Sunnybrook Health Sciences Centre
investigator full name: Dr. Gregory Czarnota
investigator title: Senior Scientist, MD
mesh term: Breast Neoplasms
sharing ipd: No