xml: <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/NCT05967884</url>
    </required_header>
    <id_info>
      <org_study_id>OMS 05-2023</org_study_id>
      <nct_id>NCT05967884</nct_id>
    </id_info>
    <brief_title>PD-1 +/- IL-4 Inhibition in ER+ Breast Cancer</brief_title>
    <official_title>A Randomized Phase II Window of Opportunity Clinical Trial of IL-4 +/- PD-1 Inhibition in Early-stage ER+ HER2- Breast Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Ottawa Hospital Research Institute</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Ontario Institute for Cancer Research</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Ottawa Hospital Research Institute</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>
        This proposal is for a Window of Opportunity (WOO) clinical trial using a novel combination&#xD;
        of two Health Canada approved agents, cemiplimab (Libtayo) and dupilumab (Dupixent), for off&#xD;
        label use in early-stage estrogen receptor positive (ER+) breast cancer.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a phase II, open-label, randomized window of opportunity trial evaluating the&#xD;
        immunologic effects within the tumour, microenvironment, and host blood of patients treated&#xD;
        with either&#xD;
  &#xD;
          -  Arm A: Cemiplimab (n=10)&#xD;
  &#xD;
          -  Arm B: Cemiplimab + Dupilumab (n=10) administered prior to surgery. Randomization will&#xD;
             be at 1:1 ratio in patients newly diagnosed with primary operable ER+* HER2- invasive&#xD;
             breast cancer awaiting surgery in the next 4-6 weeks who are not planned for neoadjuvant&#xD;
             therapy.&#xD;
  &#xD;
        Primary Hypothesis: In ER+ breast cancer, blockade of IL-4 signalling using dupilumab&#xD;
        enhances anti-tumor immunity (through reduced Th2 skewing) when used in combination with PD-1&#xD;
        inhibitors (Cemiplimab) compared to PD-1 inhibition alone in ER+ breast cancer&#xD;
  &#xD;
        Primary Objective:&#xD;
  &#xD;
        • To determine whether addition of dupilumab to cemiplimab reduces TH2 skewing of the tumor,&#xD;
        tumor microenvironment (TME) and blood in patients with ER+ breast cancer&#xD;
  &#xD;
        Secondary Objectives:&#xD;
  &#xD;
          -  To evaluate dynamic changes in immune cell populations as measured by in situ proteomics&#xD;
  &#xD;
          -  To characterize the safety of a short-term duration of the combination of dupilumab with&#xD;
             cemiplimab in patients with ER+ breast cancer awaiting surgery&#xD;
  &#xD;
        Exploratory Objective:&#xD;
  &#xD;
        • To test the effect of tumor PD-1 gene expression and its effect on the immune response in&#xD;
        treated and untreated patients&#xD;
  &#xD;
        This is a window of opportunity trial which will require administration of cemiplimab or&#xD;
        combination of cemiplimab + dupilumab prior to surgery. Surgery will be a minimum of 96 hours&#xD;
        to 2 weeks after the cemiplimab. Patient follow-up after surgery will be for a period of 30&#xD;
        days post-surgery.&#xD;
  &#xD;
        Target: 20 patients (10 in Arm A and 10 in Arm B). Accounting for screen failures and&#xD;
        withdrawals (20%), 24 patients will be accrued.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 4, 2023</start_date>
    <completion_date type="Anticipated">August 1, 2024</completion_date>
    <primary_completion_date type="Anticipated">August 1, 2024</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Immune Cell Population Analysis</measure>
      <time_frame>up to 6 months</time_frame>
      <description>The % change in various immune cell populations (CD3, CD8, macrophages and DC cells) in the tumor and microenvironment, Defined as the post-treatment value / pre-treatment value * 100%</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Study Participant Assessment of Adverse Effects</measure>
      <time_frame>up to 6 months</time_frame>
      <description>Number of participants with treatment-related adverse effects of patients treated with short term cemiplimab + dupilumab, using NCI-CTCAE</description>
    </secondary_outcome>
    <other_outcome>
      <measure>PD-1 Gene Expression</measure>
      <time_frame>up to 6 months</time_frame>
      <description>PD-1 Gene expression analysis in pre treatment tissue samples expression and its effect on the immune response in treated and untreated patients</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">20</enrollment>
    <condition>Breast Cancer</condition>
    <arm_group>
      <arm_group_label>Arm A: Cemiplimab</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Arm A: Cemiplimab (n=10), 350mg IV x 1 dose administered prior to surgery.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Arm B: Cemiplimab + Dupilumab</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Arm B: Cemiplimab + Dupilumab (n=10), Cemiplimab 350mg IV x 1 dose + Dupilumab 600 mg SC x 1 dose administered prior to surgery.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Arm A: Cemiplimab, Arm B: Cemiplimab + Dupilumab</intervention_name>
      <description>Arm A: Cemiplimab: 350mg IV x 1 dose administered prior to surgery Arm B: Cemiplimab + Dupilumab: Cemiplimab 350mg IV x 1 dose + Dupilumab 600 mg SC x 1 dose administered prior to surgery</description>
      <arm_group_label>Arm A: Cemiplimab</arm_group_label>
      <arm_group_label>Arm B: Cemiplimab + Dupilumab</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Female patients with newly diagnosed histologically confirmed primary invasive breast&#xD;
               cancer currently not undergoing any treatment while awaiting surgery.&#xD;
  &#xD;
            2. Invasive ductal or lobular carcinoma, invasive carcinoma Not Otherwise Specified (NOS)&#xD;
  &#xD;
            3. ER+ breast cancer (1-10%*) of any size. ER positive tumor defined ≥1% positively&#xD;
               staining cells by immunohistochemistry, according to the current American Society of&#xD;
               Clinical Oncology (ASCO) / College of American Pathologists (CAP) guidelines.&#xD;
  &#xD;
            4. The participant is eligible for surgery within the next 4-6 weeks.&#xD;
  &#xD;
            5. HER2/neu must be negative by immunohistochemistry (IHC) defined as IHC 0 or 1+ or&#xD;
               fluorescence in situ hybridization (FISH) or other ISH methods with a ratio of &lt; 2&#xD;
               according to current ASCO (American Society of Clinical Oncology)/CAP guidelines.&#xD;
  &#xD;
            6. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.&#xD;
  &#xD;
            7. Age ≥18 years.&#xD;
  &#xD;
            8. The participant (or legally acceptable representative if applicable) is able to&#xD;
               provide written informed consent for the study.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Known or suspected breast cancer metastasized to distant organ (lung, liver, bone,&#xD;
               brain, abdomen)&#xD;
  &#xD;
            2. Prior therapy with any chemotherapy or endocrine for breast cancer or other cancers&#xD;
               within last 3 months&#xD;
  &#xD;
            3. Pre-dominant histology other than invasive ductal or lobular carcinoma or invasive&#xD;
               carcinoma NOS.&#xD;
  &#xD;
            4. Patients with an active infection or an absolute neutrophil count &lt; 1.5 x 10^9/L.&#xD;
  &#xD;
          6. Patients with pre-existing renal impairment, Creatinine clearance calculated by Chronic&#xD;
          Kidney Disease Epidemiology Collaboration (CKD-EPI) equation of less than 50 mL/min/1.73m2.&#xD;
  &#xD;
          7. Known or current history of pneumonitis or interstitial lung disease (e.g., idiopathic&#xD;
          pulmonary fibrosis) or pneumonia in past month 8. Has known HIV or active Hepatitis B&#xD;
          (e.g., HBV detected by PCR, presence of HBsAg surface antigen and/or Anti-HBc core antigen)&#xD;
          or active Hepatitis C (e.g., HCV RNA [qualitative] is detected). Presence of Anti-HBs alone&#xD;
          suggesting immunity to Hepatis B is eligible.&#xD;
  &#xD;
          9. Any serious known immediate or delayed hypersensitivity reaction(s) to dupilumab and or&#xD;
          cemiplimab.&#xD;
  &#xD;
          10. Concurrent medical condition requiring the use of systemic immunosuppressive&#xD;
          medications, or systemic corticosteroids at doses of greater than 10 mg&#xD;
          Prednisone-equivalent. Topical steroids and other localized corticosteroids are permitted.&#xD;
          Patients who have received acute, low-dose, systemic immunosuppressant medications&#xD;
          equivalent to ≤ 10mg of prednisone within the 7 days prior to study entry (small dose of&#xD;
          dexamethasone for nausea, short course for upper respiratory tract infection etc.) may be&#xD;
          enrolled in the study. Use of steroids as prophylactic treatment for subjects with contrast&#xD;
          allergies to diagnostic imaging contrast dyes will be permitted.&#xD;
  &#xD;
          11. Concurrent use or planned use of any forbidden medications within 4 weeks prior to&#xD;
          study drug administration, which include chemotherapy, immunotherapy (tumor vaccine,&#xD;
          cytokine, or growth factor given to control cancers), other biologic therapy,&#xD;
          investigational therapy, or hormonal therapy.&#xD;
  &#xD;
          12. Confirmed pregnancy (by pregnancy test) if patient is of childbearing age or breast&#xD;
          feeding.&#xD;
  &#xD;
          13. Subjects with signs/symptoms suggestive of COVID-19 and confirmed positive COVID-19&#xD;
          test.&#xD;
  &#xD;
          14. Eastern Cooperative Oncology Group (ECOG) performance status ≥3 (see Appendix) 15. Any&#xD;
          underlying medical condition that, in the Principal Investigator's opinion, will make the&#xD;
          administration of study drug hazardous or obscure the interpretation of toxicity&#xD;
          determination or adverse events, or renders the patient ineligible to be on study.&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>90 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Angel Arnaout, MD</last_name>
      <phone>613-798-5555</phone>
      <email>anarnaout@toh.ca</email>
    </overall_contact>
    <location>
      <facility>
        <name>The Ottawa Hospital Research Institute and Cancer Center</name>
        <address>
          <city>Ottawa</city>
          <state>Ontario</state>
          <zip>K1Y 4E9</zip>
          <country>Canada</country>
        </address>
      </facility>
      <contact>
        <last_name>Angel Arnaout, MD</last_name>
        <phone>613-798-5555</phone>
        <phone_ext>79622</phone_ext>
        <email>aarnaout@toh.on.ca</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Ontario Institute for Cancer Research</name>
        <address>
          <city>Toronto</city>
          <state>Ontario</state>
          <zip>M5G 0A3</zip>
          <country>Canada</country>
        </address>
      </facility>
      <contact>
        <last_name>Melanie Spears, PhD</last_name>
        <email>melanie.spears@oicr.on.ca</email>
      </contact>
      <investigator>
        <last_name>Angel Arnaout, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Canada</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 12, 2023</study_first_submitted>
    <study_first_submitted_qc>July 22, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>July 22, 2023</last_update_submitted>
    <last_update_submitted_qc>July 22, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Window of Opportunity Clinical Trials</keyword>
    <keyword>cemiplimab</keyword>
    <keyword>dupilumab</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Breast Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Cemiplimab</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>undecided</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05967884
  org study id: OMS 05-2023
  nct id: NCT05967884
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  This proposal is for a Window of Opportunity (WOO) clinical trial using a novel combination
        of two Health Canada approved agents, cemiplimab (Libtayo) and dupilumab (Dupixent), for off
        label use in early-stage estrogen receptor positive (ER+) breast cancer.
  This is a phase II, open-label, randomized window of opportunity trial evaluating the
        immunologic effects within the tumour, microenvironment, and host blood of patients treated
        with either
  
          -  Arm A: Cemiplimab (n=10)
  
          -  Arm B: Cemiplimab + Dupilumab (n=10) administered prior to surgery. Randomization will
             be at 1:1 ratio in patients newly diagnosed with primary operable ER+* HER2- invasive
             breast cancer awaiting surgery in the next 4-6 weeks who are not planned for neoadjuvant
             therapy.
  
        Primary Hypothesis: In ER+ breast cancer, blockade of IL-4 signalling using dupilumab
        enhances anti-tumor immunity (through reduced Th2 skewing) when used in combination with PD-1
        inhibitors (Cemiplimab) compared to PD-1 inhibition alone in ER+ breast cancer
  
        Primary Objective:
  
        • To determine whether addition of dupilumab to cemiplimab reduces TH2 skewing of the tumor,
        tumor microenvironment (TME) and blood in patients with ER+ breast cancer
  
        Secondary Objectives:
  
          -  To evaluate dynamic changes in immune cell populations as measured by in situ proteomics
  
          -  To characterize the safety of a short-term duration of the combination of dupilumab with
             cemiplimab in patients with ER+ breast cancer awaiting surgery
  
        Exploratory Objective:
  
        • To test the effect of tumor PD-1 gene expression and its effect on the immune response in
        treated and untreated patients
  
        This is a window of opportunity trial which will require administration of cemiplimab or
        combination of cemiplimab + dupilumab prior to surgery. Surgery will be a minimum of 96 hours
        to 2 weeks after the cemiplimab. Patient follow-up after surgery will be for a period of 30
        days post-surgery.
  
        Target: 20 patients (10 in Arm A and 10 in Arm B). Accounting for screen failures and
        withdrawals (20%), 24 patients will be accrued.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Immune Cell Population Analysis
  time frame: up to 6 months
  description: The % change in various immune cell populations (CD3, CD8, macrophages and DC cells) in the tumor and microenvironment, Defined as the post-treatment value / pre-treatment value * 100%
  measure: Study Participant Assessment of Adverse Effects
  time frame: up to 6 months
  description: Number of participants with treatment-related adverse effects of patients treated with short term cemiplimab + dupilumab, using NCI-CTCAE
  measure: PD-1 Gene Expression
  time frame: up to 6 months
  description: PD-1 Gene expression analysis in pre treatment tissue samples expression and its effect on the immune response in treated and untreated patients
  arm group label: Arm A: Cemiplimab
  arm group type: Active Comparator
  description: Arm A: Cemiplimab (n=10), 350mg IV x 1 dose administered prior to surgery.
  arm group label: Arm B: Cemiplimab + Dupilumab
  arm group type: Experimental
  description: Arm B: Cemiplimab + Dupilumab (n=10), Cemiplimab 350mg IV x 1 dose + Dupilumab 600 mg SC x 1 dose administered prior to surgery.
  intervention type: Drug
  intervention name: Arm A: Cemiplimab, Arm B: Cemiplimab + Dupilumab
  description: Arm A: Cemiplimab: 350mg IV x 1 dose administered prior to surgery Arm B: Cemiplimab + Dupilumab: Cemiplimab 350mg IV x 1 dose + Dupilumab 600 mg SC x 1 dose administered prior to surgery
  arm group label: Arm A: Cemiplimab
  arm group label: Arm B: Cemiplimab + Dupilumab
  criteria: 
  gender: Female
  minimum age: 18 Years
  maximum age: 90 Years
  healthy volunteers: No
  last name: Angel Arnaout, MD
  phone: 613-798-5555
  email: anarnaout@toh.ca
  facility: 
  contact: 
  facility: 
  contact: 
  investigator: 
  country: Canada
  responsible party type: Sponsor
  mesh term: Breast Neoplasms
  mesh term: Cemiplimab
  sharing ipd: No
  ipd description: undecided