<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/NCT03755141</url>
  </required_header>
  <id_info>
    <org_study_id>KM10B</org_study_id>
    <nct_id>NCT03755141</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Trastuzumab Biosimilar (Herzuma®) Plus Treatment of Physician's Choice (TPC) in Patients With HER-2 Positive Metastatic Breast Cancer</brief_title>
  <official_title>Open Label, Multicenter, Prospective Phase II Study to Investigate the Efficacy and Safety of Trastuzumab Biosimilar (Herzuma®) Plus Treatment of Physician's Choice (TPC) in Patients With HER-2 Positive Metastatic Breast Cancer Who Progressed After 2 or More HER-2 Directed Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Center, Korea</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Cancer Center, Korea</source>
  <oversight_info>
    <has_dmc>No</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>
      Trastuzumab combined with chemotherapy has been approved as the first line therapy in HER2+&#xD;
      metastatic breast cancer. When patients experienced progression beyond trastuzumab containing&#xD;
      therapy, T-DM1 is considered as the second line therapy followed by trastuzumab plus any&#xD;
      other chemotherapeutic agents or lapatinib plus capecitabine.&#xD;
&#xD;
      A biosimilar drug is a biological product that is highly similar to a licensed biological&#xD;
      product, with no clinically meaningful differences in terms of safety, purity, or potency.&#xD;
      Several trastuzumab biosimilar products have been approved after efficacy and safety studies&#xD;
      which were usually as the first line setting with taxane combined.&#xD;
&#xD;
      Even though trastuzumab biosimilar drugs demonstrated similarity of equivalence with&#xD;
      trastuzumab in these studies, the efficacy of their second use beyond progression with other&#xD;
      chemotherapeutic agents has not been tested yet. In addition, the investigators don't have&#xD;
      any data regarding possible cross reactivity between trastuzumab and trastuzumab biosimilar&#xD;
      drugs.&#xD;
&#xD;
      In this study, the investigators plan multicenter phase II clinical trial to test the&#xD;
      efficacy, safety and immunogenicity of trastuzumab biosimilar, Herzuma® in combination with&#xD;
      TPC in patients with HER2+ metastatic breast cancer who progressed after 2 or more HER-2&#xD;
      directed chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">December 15, 2018</start_date>
  <completion_date type="Anticipated">June 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 15, 2021</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>Progression free survival</measure>
    <time_frame>6 months after last patient enrollment</time_frame>
    <description>defined as the time from study entry until the first observation of existing disease progression according to the above schedule or death due to any cause.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">119</enrollment>
  <condition>HER2-positive Breast Cancer</condition>
  <condition>Metastatic Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Herzuma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Herzuma + TPC</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Herzuma</intervention_name>
    <description>Herzuma + Treatment of Physician's Choice</description>
    <arm_group_label>Herzuma</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patient is an adult, ≥ 19 years old at the time of informed consent.&#xD;
&#xD;
          2. Patient has histologically and/or cytologically confirmed diagnosis of HER2-positive&#xD;
             breast cancer (HER-2/neu 3+ as defined by immunohistochemistry and/or HER-2/neu gene&#xD;
             amplification as defined by fluorescence in situ hybridization).&#xD;
&#xD;
          3. Metastatic or unresectable disease documented on diagnostic imaging studies.&#xD;
&#xD;
          4. Prior 2 or more HER-2 directed therapy for metastatic disease is mandatory.&#xD;
&#xD;
          5. Patient must have at least one measurable or evaluable lesion according to Response&#xD;
             Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1)&#xD;
&#xD;
          6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1&#xD;
&#xD;
          7. Adequate bone marrow and organ function including: a) WBC ≥ 3500/ml; b) Platelets ≥&#xD;
             100,000/ul; c) Hemoglobin &gt;9.0 g/dl; d) Total bilirubin ≤ 1.5x ULN; e) AST and ALT &lt;&#xD;
             2.5 x ULN; f) Alkaline phosphatase &lt;2.5x ULN; g) Creatinine ≤ 1.5x ULN or CCr &gt;60&#xD;
             ml/min for patients with abnormal serum Cr level function.&#xD;
&#xD;
          8. Life expectance longer than 3 months&#xD;
&#xD;
          9. Patient has an adequate left ventricular ejection function of at least 55 % at&#xD;
             baseline, as measured by echocardiography.&#xD;
&#xD;
         10. Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patient is pregnant or lactating, where pregnancy is defined as the state of a female&#xD;
             after conception and until the termination of gestation, confirmed by a positive human&#xD;
             chorionic gonadotropin (hCG) laboratory test.&#xD;
&#xD;
          2. Patient has symptomatic and unstable CNS metastases, except for treated brain&#xD;
             metastases. Treated brain metastases are defined as having no evidence of progression&#xD;
             or hemorrhage after treatment and no ongoing requirement for dexamethasone, as&#xD;
             ascertained by clinical examination and brain imaging (MRI or CT) during the screening&#xD;
             period. Anticonvulsants (stable dose) are allowed.&#xD;
&#xD;
          3. Active and clinically significant bacterial, fungal or viral infection including&#xD;
             hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus syndrome&#xD;
             (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness. Baseline viral&#xD;
             assessment is not required in patients with no known infection.&#xD;
&#xD;
          4. Major surgery within 4 weeks of first dose of investigational product or not fully&#xD;
             recovered from any side effects of previous procedures.&#xD;
&#xD;
          5. Any other malignancy within 3 years prior to first dose of investigational product&#xD;
             except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in&#xD;
             situ of the cervix.&#xD;
&#xD;
          6. QTc interval &gt;480 msec (based on the mean value of the triplicate ECGs), family or&#xD;
             personal history of long or short QT syndrome, Brugada syndrome or known history of&#xD;
             QTc prolongation or Torsade de Pointes.&#xD;
&#xD;
          7. Any of the following within 6 months of first dose of investigational product&#xD;
             myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI&#xD;
             CTCAE v. 5.0 Grade ≤2, atrial fibrillation of any grade, coronary/peripheral artery&#xD;
             bypass graft, symptomatic congestive heart failure, cerebrovascular accident including&#xD;
             transient ischemic attack, or symptomatic pulmonary embolism.&#xD;
&#xD;
          8. History of symptomatic interstitial pneumonitis.&#xD;
&#xD;
          9. Patients with a history of hypersensitivity reactions to trastuzumab, rodent-derived&#xD;
             proteins, or components of trastuzumab.&#xD;
&#xD;
         10. Other severe acute or chronic medical or psychiatric condition, including recent&#xD;
             (within the past year) or active suicidal ideation or behavior, or laboratory&#xD;
             abnormality that may increase the risk associated with study participation or&#xD;
             investigational product administration or may interfere with the interpretation of&#xD;
             study results and, in the judgment of the investigator, would make the patient&#xD;
             inappropriate for entry into this study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>In Hae Park, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Korea University Guro Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Korea University, Guro hospital</name>
      <address>
        <city>Seoul</city>
        <zip>08308</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>November 26, 2018</study_first_submitted>
  <study_first_submitted_qc>November 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 27, 2018</study_first_posted>
  <last_update_submitted>March 10, 2021</last_update_submitted>
  <last_update_submitted_qc>March 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 11, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National Cancer Center, Korea</investigator_affiliation>
    <investigator_full_name>In Hae Park</investigator_full_name>
    <investigator_title>Senior Scientist</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>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>safety profiles, efficacy data</ipd_description>
  </patient_data>
  <pending_results>
    <submitted>August 16, 2022</submitted>
    <returned>July 14, 2023</returned>
  </pending_results>
  <!-- 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/NCT03755141
org study id: KM10B
nct id: NCT03755141
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Trastuzumab combined with chemotherapy has been approved as the first line therapy in HER2+
      metastatic breast cancer. When patients experienced progression beyond trastuzumab containing
      therapy, T-DM1 is considered as the second line therapy followed by trastuzumab plus any
      other chemotherapeutic agents or lapatinib plus capecitabine.

      A biosimilar drug is a biological product that is highly similar to a licensed biological
      product, with no clinically meaningful differences in terms of safety, purity, or potency.
      Several trastuzumab biosimilar products have been approved after efficacy and safety studies
      which were usually as the first line setting with taxane combined.

      Even though trastuzumab biosimilar drugs demonstrated similarity of equivalence with
      trastuzumab in these studies, the efficacy of their second use beyond progression with other
      chemotherapeutic agents has not been tested yet. In addition, the investigators don't have
      any data regarding possible cross reactivity between trastuzumab and trastuzumab biosimilar
      drugs.

      In this study, the investigators plan multicenter phase II clinical trial to test the
      efficacy, safety and immunogenicity of trastuzumab biosimilar, Herzuma® in combination with
      TPC in patients with HER2+ metastatic breast cancer who progressed after 2 or more HER-2
      directed chemotherapy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression free survival
time frame: 6 months after last patient enrollment
description: defined as the time from study entry until the first observation of existing disease progression according to the above schedule or death due to any cause.
arm group label: Herzuma
arm group type: Experimental
description: Herzuma + TPC
intervention type: Drug
intervention name: Herzuma
description: Herzuma + Treatment of Physician's Choice
arm group label: Herzuma
criteria: 
gender: All
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
last name: In Hae Park, MD
role: Principal Investigator
affiliation: Korea University Guro Hospital
facility: 
country: Korea, Republic of
responsible party type: Principal Investigator
investigator affiliation: National Cancer Center, Korea
investigator full name: In Hae Park
investigator title: Senior Scientist
mesh term: Breast Neoplasms
sharing ipd: Undecided
ipd description: safety profiles, efficacy data
submitted: August 16, 2022
returned: July 14, 2023