<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/NCT02247037</url>
  </required_header>
  <id_info>
    <org_study_id>GCO 14-0686</org_study_id>
    <nct_id>NCT02247037</nct_id>
  </id_info>
  <brief_title>Patient-derived Xenograft (PDX) Modeling of Treatment Response for Triple Negative Breast Cancer</brief_title>
  <official_title>Patient-derived Xenograft (PDX) Modeling of Treatment Response for Triple Negative Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Icahn School of Medicine at Mount Sinai</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Champions Oncology</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Icahn School of Medicine at Mount Sinai</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will determine if patient-derived tumor xenograft (PDX) mouse models can serve as&#xD;
      a reliable model for treatment response for individual patients with triple negative breast&#xD;
      cancer. The collection of patient tumor tissue will also provide insight into the mechanisms&#xD;
      of therapeutic resistance for those individuals. Ultimately, this study will enhance our&#xD;
      understanding of the genomic basis for treatment response for triple negative cancer on an&#xD;
      individual basis, while having the potential to suggest new therapeutic options for high-risk&#xD;
      triple negative breast cancer patients with residual disease post neoadjuvant.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Triple negative breast cancer (TNBC) represents an aggressive, genomically heterogeneous,&#xD;
      subtype of breast cancer with limited therapeutic options. Many patients with TNBC receive&#xD;
      standard neoadjuvant chemotherapy (NAC) pre-operatively; response is directly correlated with&#xD;
      long-term outcome. Patients with residual disease after NAC are at higher risk for recurrent&#xD;
      or metastatic disease, but additional adjuvant therapies are not currently part of standard&#xD;
      care. Personalized treatment for patients with TNBC requires an improved understanding of the&#xD;
      genomic landscape of individual TN breast tumors, as well as improved predictive models of&#xD;
      response to specific therapeutic agents. This pilot study will determine if patient-derived&#xD;
      tumor xenograft (PDX) mouse models can serve as a reliable model for treatment response for&#xD;
      individual patients with TNBC. The tumor tissue collected (paired pre-and post NAC) will also&#xD;
      provide insight into mechanisms of therapeutic resistance for individual patients. This study&#xD;
      will enhance our understanding of the genomic basis for treatment response for TNBC on an&#xD;
      individual patient basis, and lead to potential new therapeutic options for high-risk TNBC&#xD;
      patients with post-NAC residual disease.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
        1. To collect and bank tissue specimens from patients with operable triple negative breast&#xD;
           cancer at: a) at time of diagnosis, prior to the start of neoadjuvant therapy and b) at&#xD;
           time of definitive surgery, after the completion of neoadjuvant therapy.&#xD;
&#xD;
        2. To collect and bank tissue specimen for patients with advanced metastatic triple&#xD;
           negative disease prior to start of any line therapy for metastatic disease.&#xD;
&#xD;
        3. To create patient-derived xenograft (PDX) mouse models utilizing specimens collected&#xD;
           pre- and post- neoadjuvant treatment&#xD;
&#xD;
        4. To determine if response of PDX tumors to cytotoxic agents in the Champions Oncology&#xD;
           Tumor GraftTM (COTG) assay correlates with responses observed in patients.&#xD;
&#xD;
        5. To perform genomic analyses of patient tumor specimens collected pre- and post&#xD;
           neoadjuvant treatment to study mechanisms of drug resistance&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">January 22, 2019</completion_date>
  <primary_completion_date type="Actual">January 22, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Patient Tumor Response</measure>
    <time_frame>Day 1</time_frame>
    <description>Tumor response in patients will be categorized as: Progressive Disease, Static Response, Partial Response, Complete Response</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Model Tumor Response</measure>
    <time_frame>Day 1</time_frame>
    <description>Tumor response in models will be categorized as: Progressive Disease, Static Response, Partial Response, Complete Response</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">68</enrollment>
  <condition>Triple Negative Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Triple Negative Breast Cancers</arm_group_label>
    <description>All women eligible for this protocol will fall into this group. These women will have histologically confirmed triple negative breast cancer and be eligible for neoadjuvant chemotherapy or have evidence of metastatic disease.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Chemotherapy</intervention_name>
    <description>Patients are treated with neoadjuvant chemotherapy as according to the standard of care guidelines. Patients with metastatic disease are treated according to standard of care guidelines.</description>
    <arm_group_label>Triple Negative Breast Cancers</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Core Biopsy Specimen, Surgical Specimen&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with Triple Negative Breast Cancer that are eligible for neoadjuvant chemotherapy&#xD;
        or have evidence of metastatic disease will be pursued for this protocol.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  a histological diagnosis of invasive triple negative breast cancer determined by&#xD;
             standard immunohistochemical analysis.&#xD;
&#xD;
          -  must be candidates for neoadjuvant chemotherapy according to standard of care&#xD;
             guidelines or have evidence of metastatic disease.&#xD;
&#xD;
          -  must agree to a biopsy for research purposes at time of diagnosis and to undergo&#xD;
             surgery at the hospitals of the Mount Sinai Health System.&#xD;
&#xD;
        Patients with the following MAY be eligible:&#xD;
&#xD;
        - a histological diagnosis of ER and/or PR positive breast cancer with an overall receptor&#xD;
        expression ≤ 30% breast cancer determined by standard immunohistochemical analysis&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  concurrent disease or condition that would make the patient inappropriate for study&#xD;
             participation,&#xD;
&#xD;
          -  any serious medical or psychiatric disorder that would interfere with the subject's&#xD;
             safety, or inability to provide informed consent.&#xD;
&#xD;
          -  vulnerable populations will not be included.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hanna Yoko Irie, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dubin Breast Center of The Tisch Cancer Institute at Mount Sinai</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Elisa Port, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dubin Breast Center of The Tisch Cancer Institute at Mount Sinai</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Dubin Breast Center of The Tisch Cancer Institute at Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>September 19, 2014</study_first_submitted>
  <study_first_submitted_qc>September 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 23, 2014</study_first_posted>
  <last_update_submitted>July 1, 2020</last_update_submitted>
  <last_update_submitted_qc>July 1, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 7, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Icahn School of Medicine at Mount Sinai</investigator_affiliation>
    <investigator_full_name>Hanna Irie</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Triple Negative Breast Cancer</keyword>
  <keyword>Patient Derived Xenograft</keyword>
  <keyword>Neoadjuvant Chemotherapy</keyword>
  <keyword>Therapeutic Resistance</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Triple Negative Breast Neoplasms</mesh_term>
  </condition_browse>
  <!-- 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/NCT02247037
org study id: GCO 14-0686
nct id: NCT02247037
lead sponsor: 
collaborator: 
has dmc: Yes
This study will determine if patient-derived tumor xenograft (PDX) mouse models can serve as
      a reliable model for treatment response for individual patients with triple negative breast
      cancer. The collection of patient tumor tissue will also provide insight into the mechanisms
      of therapeutic resistance for those individuals. Ultimately, this study will enhance our
      understanding of the genomic basis for treatment response for triple negative cancer on an
      individual basis, while having the potential to suggest new therapeutic options for high-risk
      triple negative breast cancer patients with residual disease post neoadjuvant.
Triple negative breast cancer (TNBC) represents an aggressive, genomically heterogeneous,
      subtype of breast cancer with limited therapeutic options. Many patients with TNBC receive
      standard neoadjuvant chemotherapy (NAC) pre-operatively; response is directly correlated with
      long-term outcome. Patients with residual disease after NAC are at higher risk for recurrent
      or metastatic disease, but additional adjuvant therapies are not currently part of standard
      care. Personalized treatment for patients with TNBC requires an improved understanding of the
      genomic landscape of individual TN breast tumors, as well as improved predictive models of
      response to specific therapeutic agents. This pilot study will determine if patient-derived
      tumor xenograft (PDX) mouse models can serve as a reliable model for treatment response for
      individual patients with TNBC. The tumor tissue collected (paired pre-and post NAC) will also
      provide insight into mechanisms of therapeutic resistance for individual patients. This study
      will enhance our understanding of the genomic basis for treatment response for TNBC on an
      individual patient basis, and lead to potential new therapeutic options for high-risk TNBC
      patients with post-NAC residual disease.

      Objectives:

        1. To collect and bank tissue specimens from patients with operable triple negative breast
           cancer at: a) at time of diagnosis, prior to the start of neoadjuvant therapy and b) at
           time of definitive surgery, after the completion of neoadjuvant therapy.

        2. To collect and bank tissue specimen for patients with advanced metastatic triple
           negative disease prior to start of any line therapy for metastatic disease.

        3. To create patient-derived xenograft (PDX) mouse models utilizing specimens collected
           pre- and post- neoadjuvant treatment

        4. To determine if response of PDX tumors to cytotoxic agents in the Champions Oncology
           Tumor GraftTM (COTG) assay correlates with responses observed in patients.

        5. To perform genomic analyses of patient tumor specimens collected pre- and post
           neoadjuvant treatment to study mechanisms of drug resistance
observational model: Case-Only
time perspective: Prospective
measure: Patient Tumor Response
time frame: Day 1
description: Tumor response in patients will be categorized as: Progressive Disease, Static Response, Partial Response, Complete Response
measure: Model Tumor Response
time frame: Day 1
description: Tumor response in models will be categorized as: Progressive Disease, Static Response, Partial Response, Complete Response
arm group label: Triple Negative Breast Cancers
description: All women eligible for this protocol will fall into this group. These women will have histologically confirmed triple negative breast cancer and be eligible for neoadjuvant chemotherapy or have evidence of metastatic disease.
intervention type: Other
intervention name: Chemotherapy
description: Patients are treated with neoadjuvant chemotherapy as according to the standard of care guidelines. Patients with metastatic disease are treated according to standard of care guidelines.
arm group label: Triple Negative Breast Cancers
Core Biopsy Specimen, Surgical Specimen
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
last name: Hanna Yoko Irie, MD, PhD
role: Principal Investigator
affiliation: Dubin Breast Center of The Tisch Cancer Institute at Mount Sinai
last name: Elisa Port, MD
role: Principal Investigator
affiliation: Dubin Breast Center of The Tisch Cancer Institute at Mount Sinai
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Icahn School of Medicine at Mount Sinai
investigator full name: Hanna Irie
investigator title: Associate Professor
mesh term: Breast Neoplasms
mesh term: Triple Negative Breast Neoplasms