<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/NCT03820141</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00020917</org_study_id>
    <nct_id>NCT03820141</nct_id>
  </id_info>
  <brief_title>Durvalumab With Trastuzumab and Pertuzumab in HER2-Enriched Breast Cancer</brief_title>
  <acronym>DTP</acronym>
  <official_title>Multicenter Phase II Trial of Durvalumab (MEDI4736) With Trastuzumab and Pertuzumab Combination in HER2-Enriched and HER2-Amplified Breast Cancer (DTP Trial)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Methodist Hospital Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>The Methodist Hospital Research Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research study is to test the safety and effectiveness of using&#xD;
      durvalumab with trastuzumab and pertuzumab in participants with human epidermal growth factor&#xD;
      receptor 2 (HER2)-enriched breast cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this research study is to test the safety and effectiveness of using&#xD;
      durvalumab with trastuzumab and pertuzumab in participants with HER2-enriched breast cancer.&#xD;
      The standard or usual pre-surgery treatment for this type of disease are drugs called&#xD;
      trastuzumab and pertuzumab that target HER2. Studies have shown that trastuzumab and&#xD;
      pertuzumab treatment can stimulate the body's own immune system to attack cancer cells.&#xD;
      Durvalumab is a drug that also activates the immune system. The use of durvalumab together&#xD;
      with trastuzumab and pertuzumab treatment may allow the immune system to work harder to kill&#xD;
      cancer cells.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 3, 2020</start_date>
  <completion_date type="Anticipated">February 2025</completion_date>
  <primary_completion_date type="Anticipated">September 2024</primary_completion_date>
  <phase>Phase 2</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pathological complete response (pCR) rate in the breast in patients with HER2-enriched and HER2-amplified breast cancer</measure>
    <time_frame>18 weeks</time_frame>
    <description>Determine pCR rate in the breast in patients with HER2-enriched and HER2-amplified breast cancer</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>pCR rate in the breast in patients whose tumors have &lt;5% and ≥5% tumor-infiltrating lymphocytes (TILs)</measure>
    <time_frame>18 weeks</time_frame>
    <description>Determine pCR rate in the breast in patients whose tumors have &lt;5% and ≥5% TILs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>pCR rate in patients with programmed cell death-ligand 1 (PD-L1)-positive and PD-L1-negative tumors</measure>
    <time_frame>18 weeks</time_frame>
    <description>Determine pCR rate in the breast in patients with PD-L1-positive and PD-L1-negative tumors</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Three-year disease-free survival (DFS) rate in patients who achieve pCR</measure>
    <time_frame>3 years</time_frame>
    <description>Determination of 3-year DFS rate in patients who achieve pCR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events</measure>
    <time_frame>18 weeks</time_frame>
    <description>Number of participants with treatment-related adverse events, as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">39</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Durvalumab + Trastuzumab + Pertuzumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Durvalumab, trastuzumab, and pertuzumab will be administered on Day 1 every 3 weeks for 6 cycles. Trastuzumab will be administered as 8 mg/kg intravenous (IV) loading dose, followed by 6 mg/kg IV. Pertuzumab will be administered as 840 mg IV loading dose, followed by 420 mg. Durvalumab will be administered at a fixed dose of 1120 mg IV.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Durvalumab</intervention_name>
    <description>programmed cell death-ligand 1 inhibitor</description>
    <arm_group_label>Durvalumab + Trastuzumab + Pertuzumab</arm_group_label>
    <other_name>IMFINZI, MEDI4736</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trastuzumab</intervention_name>
    <description>anti-HER2 monoclonal antibody</description>
    <arm_group_label>Durvalumab + Trastuzumab + Pertuzumab</arm_group_label>
    <other_name>Herceptin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pertuzumab</intervention_name>
    <description>anti-HER2 monoclonal antibody</description>
    <arm_group_label>Durvalumab + Trastuzumab + Pertuzumab</arm_group_label>
    <other_name>Perjeta</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Female aged &gt;18 years at the time of study entry.&#xD;
&#xD;
          2. Histologically confirmed HER2-enriched (by BluePrint) and HER2-amplified (ERBB2 mRNA&#xD;
             &gt;7.5-10) breast cancer.&#xD;
&#xD;
          3. Estrogen receptor and progesterone receptor negative.&#xD;
&#xD;
          4. Primary tumor greater than 1 cm diameter, measured by clinical examination and&#xD;
             mammography or echography.&#xD;
&#xD;
          5. Any nodal status&#xD;
&#xD;
          6. Bilateral breast cancers that individually meet eligibility criteria are allowed.&#xD;
&#xD;
          7. Eastern Cooperative Oncology Group performance status of 0 or 1.&#xD;
&#xD;
          8. Adequate organ and marrow function.&#xD;
&#xD;
          9. Baseline left ventricular ejection fraction greater than or equal to 50%, as measured&#xD;
             by multigated acquisition scan or echocardiogram.&#xD;
&#xD;
         10. Evidence of postmenopausal status or negative serum pregnancy test for premenopausal&#xD;
             patients. Negative serum beta-human chorionic gonadotropin pregnancy test within 7&#xD;
             days prior to the first dose of study treatment for premenopausal patients.&#xD;
&#xD;
         11. Willing to provide biopsy tissues as required by the study.&#xD;
&#xD;
         12. Willing and able to comply with the protocol for the duration of the study including&#xD;
             undergoing treatment and scheduled visits and examinations including follow-up.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Participation in another clinical study with an investigational product within 28 days&#xD;
             prior to the first dose of study treatment.&#xD;
&#xD;
          2. Concurrent enrollment in another clinical study, unless it is an observational&#xD;
             (non-interventional) clinical study or during the follow-up period of an&#xD;
             interventional study.&#xD;
&#xD;
          3. Unresolved or unstable adverse events from prior administration of another&#xD;
             investigational drug.&#xD;
&#xD;
          4. Any concurrent chemotherapy, radiation therapy, immunotherapy, or biologic therapy for&#xD;
             cancer treatment.&#xD;
&#xD;
          5. Major surgical procedure (as defined by the investigator) within 28 days prior to the&#xD;
             first dose of study treatment.&#xD;
&#xD;
          6. History of allogenic organ transplantation.&#xD;
&#xD;
          7. Active or prior documented autoimmune or inflammatory disorders.&#xD;
&#xD;
          8. History of active primary immunodeficiency.&#xD;
&#xD;
          9. Active infection including tuberculosis, hepatitis B, hepatitis C, or human&#xD;
             immunodeficiency virus.&#xD;
&#xD;
         10. Current or prior use of immunosuppressive medication within 14 days prior to the first&#xD;
             dose of study treatment.&#xD;
&#xD;
         11. Receipt of live attenuated vaccine within 30 days prior to the first dose of study&#xD;
             treatment.&#xD;
&#xD;
         12. Patients who are pregnant or breastfeeding or patients of reproductive potential who&#xD;
             are not willing to employ effective birth control from screening to 7 months after the&#xD;
             last dose of study treatment.&#xD;
&#xD;
         13. Known allergy or hypersensitivity to any of the study drugs or any of the study drug&#xD;
             excipients.&#xD;
&#xD;
         14. Patients with a mean QT interval of greater than or equal to 470ms calculated from 3&#xD;
             EKGs&#xD;
&#xD;
         15. Patients with underlying cardiovascular conditions that have recently undergone&#xD;
             interventions including: cardiac ventricular arrhythmia requiring medication, history&#xD;
             of second or third degree AV blocks, myocardial infarction with the previous year,&#xD;
             congestive heart failure, and unstable angina&#xD;
&#xD;
         16. Patients with a LVEF less than 50%&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jenny Chang, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Houston Methodist Cancer Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Houston Methodist Cancer Center</last_name>
    <phone>713-441-0629</phone>
    <email>ccresearch@houstonmethodist.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jenny Chang, M.D.</last_name>
    <phone>713-441-0629</phone>
    <email>ccresearch@houstonmethodist.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Houston Methodist Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jenny C Chang, MD</last_name>
      <phone>713-441-0629</phone>
      <email>ccresearch@houstonmethodist.org</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>January 25, 2019</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 29, 2019</study_first_posted>
  <last_update_submitted>September 15, 2023</last_update_submitted>
  <last_update_submitted_qc>September 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Methodist Hospital Research Institute</investigator_affiliation>
    <investigator_full_name>Jenny C. Chang, MD</investigator_full_name>
    <investigator_title>Director, Houston Methodist Cancer Center</investigator_title>
  </responsible_party>
  <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>Trastuzumab</mesh_term>
    <mesh_term>Durvalumab</mesh_term>
    <mesh_term>Pertuzumab</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/NCT03820141
org study id: Pro00020917
nct id: NCT03820141
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this research study is to test the safety and effectiveness of using
      durvalumab with trastuzumab and pertuzumab in participants with human epidermal growth factor
      receptor 2 (HER2)-enriched breast cancer.
The purpose of this research study is to test the safety and effectiveness of using
      durvalumab with trastuzumab and pertuzumab in participants with HER2-enriched breast cancer.
      The standard or usual pre-surgery treatment for this type of disease are drugs called
      trastuzumab and pertuzumab that target HER2. Studies have shown that trastuzumab and
      pertuzumab treatment can stimulate the body's own immune system to attack cancer cells.
      Durvalumab is a drug that also activates the immune system. The use of durvalumab together
      with trastuzumab and pertuzumab treatment may allow the immune system to work harder to kill
      cancer cells.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pathological complete response (pCR) rate in the breast in patients with HER2-enriched and HER2-amplified breast cancer
time frame: 18 weeks
description: Determine pCR rate in the breast in patients with HER2-enriched and HER2-amplified breast cancer
measure: pCR rate in the breast in patients whose tumors have <5% and ≥5% tumor-infiltrating lymphocytes (TILs)
time frame: 18 weeks
description: Determine pCR rate in the breast in patients whose tumors have <5% and ≥5% TILs
measure: pCR rate in patients with programmed cell death-ligand 1 (PD-L1)-positive and PD-L1-negative tumors
time frame: 18 weeks
description: Determine pCR rate in the breast in patients with PD-L1-positive and PD-L1-negative tumors
measure: Three-year disease-free survival (DFS) rate in patients who achieve pCR
time frame: 3 years
description: Determination of 3-year DFS rate in patients who achieve pCR
measure: Number of participants with treatment-related adverse events
time frame: 18 weeks
description: Number of participants with treatment-related adverse events, as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0
arm group label: Durvalumab + Trastuzumab + Pertuzumab
arm group type: Experimental
description: Durvalumab, trastuzumab, and pertuzumab will be administered on Day 1 every 3 weeks for 6 cycles. Trastuzumab will be administered as 8 mg/kg intravenous (IV) loading dose, followed by 6 mg/kg IV. Pertuzumab will be administered as 840 mg IV loading dose, followed by 420 mg. Durvalumab will be administered at a fixed dose of 1120 mg IV.
intervention type: Drug
intervention name: Durvalumab
description: programmed cell death-ligand 1 inhibitor
arm group label: Durvalumab + Trastuzumab + Pertuzumab
other name: IMFINZI, MEDI4736
intervention type: Drug
intervention name: Trastuzumab
description: anti-HER2 monoclonal antibody
arm group label: Durvalumab + Trastuzumab + Pertuzumab
other name: Herceptin
intervention type: Drug
intervention name: Pertuzumab
description: anti-HER2 monoclonal antibody
arm group label: Durvalumab + Trastuzumab + Pertuzumab
other name: Perjeta
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jenny Chang, M.D.
role: Principal Investigator
affiliation: Houston Methodist Cancer Center
last name: Houston Methodist Cancer Center
phone: 713-441-0629
email: ccresearch@houstonmethodist.org
last name: Jenny Chang, M.D.
phone: 713-441-0629
email: ccresearch@houstonmethodist.org
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: The Methodist Hospital Research Institute
investigator full name: Jenny C. Chang, MD
investigator title: Director, Houston Methodist Cancer Center
mesh term: Breast Neoplasms
mesh term: Trastuzumab
mesh term: Durvalumab
mesh term: Pertuzumab
sharing ipd: No