<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/NCT04410874</url>
  </required_header>
  <id_info>
    <org_study_id>2020-4599</org_study_id>
    <nct_id>NCT04410874</nct_id>
  </id_info>
  <brief_title>Imvamune Vaccine for the Treatment of Non-melanoma Skin Cancer</brief_title>
  <acronym>MUSIC-01</acronym>
  <official_title>MVA-BN Imvamune Smallpox Vaccine Virus for Treatment of Basal Cell Carcinoma, Squamous Cell Carcinomas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ivan Litvinov</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>McGill University Health Centre/Research Institute of the McGill University Health 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>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study examines the safety and efficacy of using the Imvamune smallpox vaccine in the&#xD;
      treatment of non-melanoma skin cancers (basal cell carcinoma and squamous cell carcinoma).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      One of the main ways cancer is able to develop is by hiding or evading our immune system&#xD;
      which usually detects and kills potential tumor cells. Once cancer has developed the ability&#xD;
      to evade the immune system it can continue to grow and become a tumor. One potential strategy&#xD;
      currently being researched, called immunotherapy, uses viruses to stimulate an immune&#xD;
      response which attacks the tumor.&#xD;
&#xD;
      Imvamune is a live, non-replicating virus used in Canada to vaccinate adults and children&#xD;
      against smallpox. It is safe to use in immunosuppressed patients because the virus is unable&#xD;
      to replicate and spread past the first infected cell. This makes the Imvamune vaccine a&#xD;
      viable candidate for immunotherapy in immunosuppressed patients who are at a much higher (up&#xD;
      to 60x) risk of developing non-melanoma skin cancers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 16, 2020</start_date>
  <completion_date type="Anticipated">July 2023</completion_date>
  <primary_completion_date type="Anticipated">November 2022</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Tolerated Dose (MTD)</measure>
    <time_frame>25 days</time_frame>
    <description>The MTD will be defined as the dose at which 2 or more patients experience a grade 3 or 4 adverse event (as defined by NCI Common Terminology Criteria for Adverse Events version 5.0) that is at least &quot;probably related&quot; to the study drug (ex: dose limiting toxicity).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Objective Tumor Response Rate (ORR)</measure>
    <time_frame>25 days</time_frame>
    <description>Clinical and histological evaluation of the tumor to assess the development of immunity against BCC and/or SCC tumors or their protein markers.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Viral load in NMSC tumours</measure>
    <time_frame>25 days</time_frame>
    <description>Ability to detect viral infection in the tumor.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of T cells/concentration of antigen specific antibodies</measure>
    <time_frame>25 days</time_frame>
    <description>Ability to elicit increased immunological T/NKT cell mediated response, and antibody response against the tumor.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">45</enrollment>
  <condition>Non-melanoma Skin Cancer</condition>
  <condition>Basal Cell Carcinoma</condition>
  <condition>Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Imvamune</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Imvamune vaccine to be administered intratumorally at one of three doses on Days 0 and 4 of the study</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Imvamune</intervention_name>
    <description>Imvamune vaccine to be administered (via injection) intratumorally at one of three doses (1x10^7, 1x10^8, or 4x10^8 PFU) twice, 4 days apart (first injection on Day 0 of the study and second injection on Day 4)</description>
    <arm_group_label>Imvamune</arm_group_label>
    <other_name>MVA-BN Smallpox vaccine</other_name>
    <other_name>Modified Vaccinia Ankara Smallpox Vaccine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects must have histologically confirmed, BCC and/or SCC tumors located on the&#xD;
             chest, back, thigh, or arm/forearm.&#xD;
&#xD;
          -  Presence of clinically documented disease. Skin tumor should measure at least 10 mm in&#xD;
             size and should be no larger than 5 cm in any axes. There should be no clinical&#xD;
             suspicion of metastasis (i.e. no lymphadenopaties and no systemic symptoms).&#xD;
&#xD;
          -  Age &gt; 18 years.&#xD;
&#xD;
          -  Subjects must have a documented ECOG performance status of 0 or 1.&#xD;
&#xD;
          -  Subjects could be treatment naive or could have had previous surgery or radiation&#xD;
&#xD;
          -  Subjects may have had prior radiation therapy. A minimum of 28 days (4 weeks) must&#xD;
             have elapsed between the last dose of radiation and date of registration (14 days for&#xD;
             a single palliative fraction of radiation to a non-target lesion). Subjects must have&#xD;
             recovered from any acute toxic effects from radiation prior to registration (unless&#xD;
             grade 1, irreversible and considered not clinically significant).&#xD;
&#xD;
          -  Previous surgery is permitted. A minimum of 28 days (4 weeks) must have elapsed&#xD;
             between any major surgery and date of registration (7 days for minor surgery),&#xD;
             provided that wound healing has occurred&#xD;
&#xD;
          -  Each subject must sign a consent form prior to registration/at registration and prior&#xD;
             to tests which are study specific.&#xD;
&#xD;
          -  Subjects must be accessible for treatment and follow-up. Subjects registered on this&#xD;
             trial must be treated and followed at the McGill University Health Centre (MUHC) or&#xD;
             McGill Affiliated/other participating hospitals&#xD;
&#xD;
          -  Laboratory requirements (must be done within 7 days prior to registration or at time&#xD;
             of registration) as follows:&#xD;
&#xD;
          -  White blood cell count ≥3.0x10^9/L&#xD;
&#xD;
          -  absolute neutrophils ≥1.5x10^9/L&#xD;
&#xD;
          -  hemoglobin ≥100g/L&#xD;
&#xD;
          -  platelets ≥75x10^9/L&#xD;
&#xD;
          -  INR ≤1.2&#xD;
&#xD;
          -  bilirubin ≤1.5x upper normal limit&#xD;
&#xD;
          -  AST and ALT ≤3.0x upper normal limit&#xD;
&#xD;
          -  serum creatinine ≤1.5x upper normal limit (or creatinine clearance of ≥60mL/min)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Cancers located on cosmetically/functionally important areas (i.e. face, neck,&#xD;
             genitalia, hands, feet, and lower legs).&#xD;
&#xD;
          -  Tumor larger than 5 cm in size (any axes).&#xD;
&#xD;
          -  Metastatic disease (or suspicion of metastasis).&#xD;
&#xD;
          -  Tumors arising as part of a genetic syndrome (i.e., Bazex-Dupré-Christol, Basal Cell&#xD;
             Nevus Syndrome, Rombo syndromes for BCC or Xeroderma Pigmentosa, Ferguson Smith,&#xD;
             Grzybowski, Muir-Tore syndromes for SCC).&#xD;
&#xD;
          -  Immunosuppressed individuals (e.g. organ transplant recipients, patient with inherited&#xD;
             immunodeficiencies, HIV+ individuals or individuals receiving immunosuppressive&#xD;
             medications for other reasons).&#xD;
&#xD;
          -  Individuals that are not able or willing to sign an informed consent.&#xD;
&#xD;
          -  Subjects with history of other active or current malignancies requiring active&#xD;
             treatment.&#xD;
&#xD;
          -  Patients undergoing concurrent treatments with other anti-cancer therapy or other&#xD;
             investigational agents.&#xD;
&#xD;
          -  Subjects with prior treatment with Imvamune&#xD;
&#xD;
          -  Subjects with serious illness or medical condition that would not permit management&#xD;
&#xD;
          -  Subjects with uncontrolled pre-existing cardiovascular conditions and/or symptomatic&#xD;
             cardiac dysfunction.&#xD;
&#xD;
          -  Pregnant or lactating women. Men or women of childbearing potential who do not agree&#xD;
             to use adequate contraception while on trial and 6 weeks following the trial.&#xD;
&#xD;
          -  Subjects using anti-viral medications, steroids, immunosuppressive agents, or&#xD;
             immunization (including the flu shot) within 14 days prior to registration. Patients&#xD;
             who are at high risk of influenza infection (65 years and older, people of any age&#xD;
             with certain chronic medical conditions (such as asthma, diabetes, or heart disease),&#xD;
             pregnant women and children younger than 5 years), and who have not received an&#xD;
             influenza vaccination during the flu season (i.e., October to May).&#xD;
&#xD;
          -  Subjects with a condition that could have resulted in splenic dysfunction (e.g.&#xD;
             splenectomy, sickle cell anemia, radiation to the spleen ≥ 20Gy, congenital&#xD;
             asplenism).&#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>Ivan V Litvinov, M.D., Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>McGill University Health Centre/Research Institute of the McGill University Health Centre</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ivan V. Litvinov, M.D., Ph.D</last_name>
    <phone>514-934-1934</phone>
    <phone_ext>76140</phone_ext>
    <email>ivan.litvinov@mcgill.ca</email>
  </overall_contact>
  <location>
    <facility>
      <name>McGill University Health Centre</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ivan V Litvinov, Md, PhD</last_name>
      <phone>514-934-1934</phone>
      <phone_ext>76140</phone_ext>
      <email>ivan.litvinov@mcgill.ca</email>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>May 27, 2020</study_first_submitted>
  <study_first_submitted_qc>May 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 1, 2020</study_first_posted>
  <last_update_submitted>November 26, 2020</last_update_submitted>
  <last_update_submitted_qc>November 26, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 1, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>McGill University Health Centre/Research Institute of the McGill University Health Centre</investigator_affiliation>
    <investigator_full_name>Ivan Litvinov</investigator_full_name>
    <investigator_title>Scientist</investigator_title>
  </responsible_party>
  <keyword>Skin Cancer</keyword>
  <keyword>Immunotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Carcinoma, Basal Cell</mesh_term>
    <mesh_term>Skin Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic</mesh_term>
    <mesh_term>Vaccines</mesh_term>
  </intervention_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/NCT04410874
org study id: 2020-4599
nct id: NCT04410874
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This study examines the safety and efficacy of using the Imvamune smallpox vaccine in the
      treatment of non-melanoma skin cancers (basal cell carcinoma and squamous cell carcinoma).
One of the main ways cancer is able to develop is by hiding or evading our immune system
      which usually detects and kills potential tumor cells. Once cancer has developed the ability
      to evade the immune system it can continue to grow and become a tumor. One potential strategy
      currently being researched, called immunotherapy, uses viruses to stimulate an immune
      response which attacks the tumor.

      Imvamune is a live, non-replicating virus used in Canada to vaccinate adults and children
      against smallpox. It is safe to use in immunosuppressed patients because the virus is unable
      to replicate and spread past the first infected cell. This makes the Imvamune vaccine a
      viable candidate for immunotherapy in immunosuppressed patients who are at a much higher (up
      to 60x) risk of developing non-melanoma skin cancers.
allocation: N/A
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose (MTD)
time frame: 25 days
description: The MTD will be defined as the dose at which 2 or more patients experience a grade 3 or 4 adverse event (as defined by NCI Common Terminology Criteria for Adverse Events version 5.0) that is at least "probably related" to the study drug (ex: dose limiting toxicity).
measure: Objective Tumor Response Rate (ORR)
time frame: 25 days
description: Clinical and histological evaluation of the tumor to assess the development of immunity against BCC and/or SCC tumors or their protein markers.
measure: Viral load in NMSC tumours
time frame: 25 days
description: Ability to detect viral infection in the tumor.
measure: Number of T cells/concentration of antigen specific antibodies
time frame: 25 days
description: Ability to elicit increased immunological T/NKT cell mediated response, and antibody response against the tumor.
arm group label: Imvamune
arm group type: Experimental
description: Imvamune vaccine to be administered intratumorally at one of three doses on Days 0 and 4 of the study
intervention type: Biological
intervention name: Imvamune
description: Imvamune vaccine to be administered (via injection) intratumorally at one of three doses (1x10^7, 1x10^8, or 4x10^8 PFU) twice, 4 days apart (first injection on Day 0 of the study and second injection on Day 4)
arm group label: Imvamune
other name: MVA-BN Smallpox vaccine
other name: Modified Vaccinia Ankara Smallpox Vaccine
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ivan V Litvinov, M.D., Ph.D
role: Principal Investigator
affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
last name: Ivan V. Litvinov, M.D., Ph.D
phone: 514-934-1934
phone ext: 76140
email: ivan.litvinov@mcgill.ca
facility: 
status: Recruiting
contact: 
country: Canada
responsible party type: Sponsor-Investigator
investigator affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
investigator full name: Ivan Litvinov
investigator title: Scientist
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Carcinoma, Basal Cell
mesh term: Skin Neoplasms
mesh term: Smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic
mesh term: Vaccines
sharing ipd: No