<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/NCT04431648</url>
  </required_header>
  <id_info>
    <org_study_id>076-2019</org_study_id>
    <nct_id>NCT04431648</nct_id>
  </id_info>
  <brief_title>Novel MRI-Guided Ultrasound Stimulated Microbubble Radiation Treatment for Patients With Head and Neck Cancer</brief_title>
  <acronym>USmBRT-H</acronym>
  <official_title>Novel MRI-Guided Ultrasound Stimulated Microbubble Radiation Treatment for Patients With Head and Neck 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>
  </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>
      This study is to demonstrate the feasibility of novel MRI-guided ultrasound stimulated&#xD;
      microbubble treatment to enhance radiation effects in humans receiving external beam&#xD;
      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 head and neck cancer. The secondary aim is to evaluate tumor&#xD;
      (primary and/or nodal) response to MRg-FU + MB and radiation, as measured radiologically&#xD;
      within the treated therapeutic regions.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 1, 2020</start_date>
  <completion_date type="Anticipated">May 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">May 1, 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 Head and Neck Cancers</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 head and neck 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 head and neck 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>Head and Neck Cancer</condition>
  <arm_group>
    <arm_group_label>MRg-FUS MB Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with head and neck cancer 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 PERFLUTREN INJECTABLE SUSPENSION</intervention_name>
    <description>MRI-guided ultrasound-stimulated microbubble-treatment</description>
    <arm_group_label>MRg-FUS MB Treatment</arm_group_label>
    <other_name>Contrast Enhancing Agent for Intravenous Use, DIN 02243173</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥18 years&#xD;
&#xD;
          -  All biopsy-confirmed squamous cell carcinoma (SCC) of the H&amp;N within past three months&#xD;
             including the following subregions: Larynx, Oropharynx, Hypopharynx, Oral Cavity,&#xD;
             Salivary Glands, and Paranasal Sinuses&#xD;
&#xD;
          -  Stage I-IV H&amp;N cancers (i.e. cT1-T4, cN0-N3, cM0), per AJCC guidelines (8th Edition).&#xD;
&#xD;
          -  Assessed by the treating surgeon, and radiation oncologist, and following a&#xD;
             multidisciplinary discussion, determined to have unresectable and/or inoperable&#xD;
             disease in the head and neck region.&#xD;
&#xD;
          -  Patients referred for standard radiotherapy, including the following dose regimens: 70&#xD;
             Gy/35 fractions, 50 Gy/20 fractions, or 35-40 Gy/5 fractions (SBRT,&#xD;
             hypofractionation).&#xD;
&#xD;
          -  Patients treated with concurrent pre-operative chemoradiation, including: Cisplatin&#xD;
             (40 mg/m2 q.w.k or Carboplatin 70 mg/m2 / day IV on days 1-4, 22-25 and at days 43-46&#xD;
             of radiation).&#xD;
&#xD;
          -  Able to understand and give informed consent.&#xD;
&#xD;
          -  Weight &lt;140kg.&#xD;
&#xD;
          -  Radiologic evidence of neck lymphadenopathy with at least one target lesion measuring&#xD;
             &gt; 1cm in largest dimension (Recurrent or initial presentation)&#xD;
&#xD;
          -  Target lesion visible by non-contrast MRI.&#xD;
&#xD;
          -  Target lesion accessible for MRg-FU procedure.&#xD;
&#xD;
          -  Able to communicate sensation during MRg-FU treatment.&#xD;
&#xD;
          -  Patients 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 contrast-enhanced MRI scan - standard of care criteria&#xD;
&#xD;
          -  Head and neck surgery (excluding biopsy) ≤ 6 weeks prior to study enrolment&#xD;
&#xD;
          -  Chemotherapy or other systemic anti-cancer agents ≤ 1 week prior to enrolment unless&#xD;
             cisplatin-based chemotherapy&#xD;
&#xD;
          -  Previous radiotherapy ≤ 6 weeks prior to enrollment&#xD;
&#xD;
          -  Target lesion involves the skin surface causing ulceration, bleeding or discharge&#xD;
&#xD;
          -  Target lesion in contact with hollow viscera&#xD;
&#xD;
          -  Target lesion located in the skull, spine, or mandible&#xD;
&#xD;
          -  The fibrotic scar along the proposed FU beam path&#xD;
&#xD;
          -  Orthopedic implant along proposed FU beam path or at a site of the target lesion.&#xD;
&#xD;
          -  Severe cardiovascular, neurological, renal or hematological chronic disease&#xD;
&#xD;
          -  ECOG (Eastern Cooperative Oncology Group) Performance Status ≥ 3. Unable to tolerate&#xD;
             required stationary position during treatment&#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. QT prolongation observed on screening ECG (QTc &gt; 450ms for men or &gt;470ms&#xD;
             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>Gregory J Czarnota, PhD, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sunnybrook Health Sciences Centre</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Shopnil Prasla</last_name>
    <phone>416-480-6100</phone>
    <phone_ext>89533</phone_ext>
    <email>shopnil.prasla@sri.utoronto.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Maria L Anzola Pena</last_name>
    <phone>416-480-6100</phone>
    <phone_ext>89533</phone_ext>
    <email>marialourdes.anzolapena@sri.utoronto.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Gregory J Czarnota</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>gregory.czarnota@sunnybrook.ca</email>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>April 2023</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>April 24, 2023</last_update_submitted>
  <last_update_submitted_qc>April 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 26, 2023</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>Head and Neck Cancer</keyword>
  <keyword>Focused Ultrasound</keyword>
  <keyword>Microbubble</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Head and Neck 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/NCT04431648
org study id: 076-2019
nct id: NCT04431648
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
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 head and neck 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 Head and Neck Cancers
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of toxicity and adverse events using MRg-FUS MB treatment in patients with head and neck 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 head and neck 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 head and neck cancer will receive MRI-guided ultrasound-stimulated microbubble-treatment combined with radiotherapy on a LINAC.
intervention type: Drug
intervention name: DEFINITY PERFLUTREN INJECTABLE SUSPENSION
description: MRI-guided ultrasound-stimulated microbubble-treatment
arm group label: MRg-FUS MB Treatment
other name: Contrast Enhancing Agent for Intravenous Use, DIN 02243173
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gregory J Czarnota, PhD, MD
role: Principal Investigator
affiliation: Sunnybrook Health Sciences Centre
last name: Shopnil Prasla
phone: 416-480-6100
phone ext: 89533
email: shopnil.prasla@sri.utoronto.ca
last name: Maria L Anzola Pena
phone: 416-480-6100
phone ext: 89533
email: marialourdes.anzolapena@sri.utoronto.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: Head and Neck Neoplasms
sharing ipd: No