<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/NCT03250676</url>
  </required_header>
  <id_info>
    <org_study_id>H3B-6545-A001-101</org_study_id>
    <secondary_id>2018-000570-29</secondary_id>
    <nct_id>NCT03250676</nct_id>
  </id_info>
  <brief_title>Trial of H3B-6545, in Women With Locally Advanced or Metastatic Estrogen Receptor-positive, HER2 Negative Breast Cancer</brief_title>
  <official_title>A Phase 1-2 Multicenter, Open Label Trial of H3B-6545, a Covalent Antagonist of Estrogen Receptor Alpha, in Women With Locally Advanced or Metastatic Estrogen Receptor-positive, HER2 Negative Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Eisai Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Eisai Inc.</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 primary purpose of phase 1 portion of this study is to determine the maximum tolerated&#xD;
      dose (MTD) and recommended phase 2 dose (RP2D) of H3B-6545 in women with locally advanced or&#xD;
      metastatic estrogen receptor (ER)-positive, human epidermal growth factor 2 (HER2)-negative&#xD;
      breast cancer.&#xD;
&#xD;
      The primary purpose of phase 2 portion of this study is to estimate the efficacy of H3B-6545&#xD;
      in terms of best overall response rate, duration of response (DoR), clinical benefit rate&#xD;
      (CBR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS)&#xD;
      in all participants with ER-positive, HER2-negative breast cancer and in those with and&#xD;
      without ER alpha mutation (including a clonal estrogen receptor 1 gene [ESR1] Y537S&#xD;
      mutation).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 17, 2017</start_date>
  <completion_date type="Anticipated">October 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">October 1, 2023</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>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants with Dose-limiting Toxicities (DLTs)</measure>
    <time_frame>Phase 1 Cycle 1 (28 days)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)</measure>
    <time_frame>Phase 1 and 2 continuously throughout the study until 28 days after treatment discontinuation (up to 36 months)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area under the Plasma Concentration-time Curve from Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6545</measure>
    <time_frame>Phase 1, Cycle 1 (28-day cycles): Days 1 and 15 pre-dose and at multiple time points (up to 24 hours) post-dose; or Phase 2 Cycle 1 (28-day cycles): Days 15 or 22 pre-dose and at multiple time points (up to 24 hours) post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Maximum Observed Plasma Concentration (Cmax) of H3B-6545</measure>
    <time_frame>Phase 1, Cycle 1 (28-day cycles): Days 1 and 15 (pre-dose and at multiple time points (up to 24 hours) post-dose; or Phase 2 Cycle 1 (28-day cycles): Days 15 or 22 pre-dose and at multiple time points (up to 24 hours) post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of Maximum Observed Plasma Concentration (tmax) of H3B-6545</measure>
    <time_frame>Phase 1, Cycle 1 (28-day cycles): Days 1 and 15 pre-dose and at multiple time points (up to 24 hours) post-dose; or Phase 2 Cycle 1 (28-day cycles): Days 15 or 22 pre-dose and at multiple time points (up to 24 hours) post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>Phase 1 and 2 up to approximately 36 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DoR)</measure>
    <time_frame>Phase 1 and 2 up to approximately 36 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>Phase 1 and 2 up to approximately 36 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Benefit Rate (CBR)</measure>
    <time_frame>Phase 1 and 2 up to approximately 36 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>Phase 1 and 2 up to approximately 36 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Phase 1 and 2 up to approximately 36 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">206</enrollment>
  <condition>Breast Neoplasms</condition>
  <condition>Breast Cancer</condition>
  <condition>Estrogen-receptor Positive Breast Cancer</condition>
  <condition>Cancer, Breast</condition>
  <condition>Breast Cancer Female</condition>
  <condition>Breast Adenocarcinoma</condition>
  <condition>Estrogen Receptor Positive Tumor</condition>
  <condition>ER Positive</condition>
  <arm_group>
    <arm_group_label>H3B-6545 Arm 1: Dose escalation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>H3B-6545 Arm 2: Phase 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>H3B-6545</intervention_name>
    <description>Oral capsules by mouth once daily</description>
    <arm_group_label>H3B-6545 Arm 1: Dose escalation</arm_group_label>
    <arm_group_label>H3B-6545 Arm 2: Phase 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Pre- or post-menopausal women.&#xD;
&#xD;
          2. ER-positive, HER2-negative breast cancer that is advanced or metastatic.&#xD;
&#xD;
          3. Progressed on prior therapy. Multiple prior lines of therapy allowed in Phase 1 and 2.&#xD;
             Participants under amendment 6 (or subsequent amendments) must have received prior&#xD;
             cyclin-dependent kinase (CDK4/6) inhibitor therapy. Up to one prior chemotherapy in&#xD;
             the metastatic setting is allowed.&#xD;
&#xD;
          4. A recent archival tumor tissue obtained within 6 months prior to enrollment or a fresh&#xD;
             tumor biopsy must be provided. A second biopsy after initiating trial therapy is not&#xD;
             required.&#xD;
&#xD;
          5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.&#xD;
&#xD;
          6. Adequate bone marrow and organ function.&#xD;
&#xD;
          7. Participants under amendment 6 (or subsequent amendments) must have measurable disease&#xD;
             at baseline as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.&#xD;
&#xD;
          8. Participants under amendment 6 (or subsequent amendments) must have ESR1 Y537S&#xD;
             mutation in absence of ESR1 D538G mutation as per the results of a central laboratory&#xD;
             from a Nucleic Acids Whole Blood sample.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Participants must have at least one measurable lesion.&#xD;
&#xD;
          2. Participant with inflammatory breast cancer.&#xD;
&#xD;
          3. Participant has received more than one prior chemotherapy regimen for metastatic&#xD;
             disease (Phase 2 only).&#xD;
&#xD;
          4. Females of childbearing potential who are unable or unwilling to follow adequate&#xD;
             contraceptive measures.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Western Regional Medical Center, Inc., DBA Cancer Treatment Centers of America, Phoenix</name>
      <address>
        <city>Goodyear</city>
        <state>Arizona</state>
        <zip>85338</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94158</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado - Cancer Center</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Holy Cross Hospital Inc</name>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <zip>33308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists South</name>
      <address>
        <city>Fort Myers</city>
        <state>Florida</state>
        <zip>33901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists North</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <zip>33705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists and Research Institute</name>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <zip>34232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southeastern Regional Medical Center, Inc., DBA Cancer Treatment Centers of America, Atlanta</name>
      <address>
        <city>Newnan</city>
        <state>Georgia</state>
        <zip>30265</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carle Cancer Center</name>
      <address>
        <city>Urbana</city>
        <state>Illinois</state>
        <zip>61801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Midwestern Regional Medical Center, Inc., DBA Cancer Treatment Centers of Americal, Chicago</name>
      <address>
        <city>Zion</city>
        <state>Illinois</state>
        <zip>60099</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins Sidney Kimmel Comprehensive Cancer Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Luke's Cancer Institute</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Medical Center</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Cancer Center of Nevada</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of North Carolina</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Parkland Health and Hospital System</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tyler Oncology/Oncology PA</name>
      <address>
        <city>Tyler</city>
        <state>Texas</state>
        <zip>75701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Huntsman Cancer Institute at The University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Edog - Ico - Ppds</name>
      <address>
        <city>Angers</city>
        <zip>49055</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Jean Minjoz</name>
      <address>
        <city>Besançon</city>
        <zip>25030</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Jean Perrin</name>
      <address>
        <city>Clermont-Ferrand</city>
        <zip>63011</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Oscar Lambret</name>
      <address>
        <city>Lille</city>
        <zip>59000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Saint Louis</name>
      <address>
        <city>Paris</city>
        <zip>75010</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital de la Pitié Salpétrière</name>
      <address>
        <city>Paris</city>
        <zip>75013</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>EDOG - Centre Eugene Marquis Centre Regional de Lutte Contre Le Cancer - PPDS</name>
      <address>
        <city>Rennes</city>
        <zip>35042</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>EDOG Institut de Cancerologie de l'Ouest - PPDS</name>
      <address>
        <city>St. Herblain</city>
        <zip>44805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut de Cancérologie Strasbourg Europe</name>
      <address>
        <city>Strasbourg</city>
        <zip>67200</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy</name>
      <address>
        <city>Villejuif Cedex</city>
        <zip>94805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Royal Marsden NHS Foundation Trust</name>
      <address>
        <city>Chelsea</city>
        <state>London</state>
        <zip>SW3 6JJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Velindre Cancer Centre</name>
      <address>
        <city>Cardiff</city>
        <zip>CF14 2TL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Barts Health NHS Trust</name>
      <address>
        <city>London</city>
        <zip>EC1A 7BE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute</name>
      <address>
        <city>London</city>
        <zip>W1G 6AD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christie Hospital</name>
      <address>
        <city>Manchester</city>
        <zip>M20 4BX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Royal Marsden NHS Foundation Trust</name>
      <address>
        <city>Sutton</city>
        <zip>SM2 5PT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>August 11, 2017</study_first_submitted>
  <study_first_submitted_qc>August 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 16, 2017</study_first_posted>
  <last_update_submitted>March 22, 2023</last_update_submitted>
  <last_update_submitted_qc>March 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>estrogen receptor</keyword>
  <keyword>H3B-6545</keyword>
  <keyword>breast cancer</keyword>
  <keyword>Endocrine Therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>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/NCT03250676
org study id: H3B-6545-A001-101
secondary id: 2018-000570-29
nct id: NCT03250676
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The primary purpose of phase 1 portion of this study is to determine the maximum tolerated
      dose (MTD) and recommended phase 2 dose (RP2D) of H3B-6545 in women with locally advanced or
      metastatic estrogen receptor (ER)-positive, human epidermal growth factor 2 (HER2)-negative
      breast cancer.

      The primary purpose of phase 2 portion of this study is to estimate the efficacy of H3B-6545
      in terms of best overall response rate, duration of response (DoR), clinical benefit rate
      (CBR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS)
      in all participants with ER-positive, HER2-negative breast cancer and in those with and
      without ER alpha mutation (including a clonal estrogen receptor 1 gene [ESR1] Y537S
      mutation).
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants with Dose-limiting Toxicities (DLTs)
time frame: Phase 1 Cycle 1 (28 days)
measure: Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
time frame: Phase 1 and 2 continuously throughout the study until 28 days after treatment discontinuation (up to 36 months)
measure: Area under the Plasma Concentration-time Curve from Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6545
time frame: Phase 1, Cycle 1 (28-day cycles): Days 1 and 15 pre-dose and at multiple time points (up to 24 hours) post-dose; or Phase 2 Cycle 1 (28-day cycles): Days 15 or 22 pre-dose and at multiple time points (up to 24 hours) post-dose
measure: Mean Maximum Observed Plasma Concentration (Cmax) of H3B-6545
time frame: Phase 1, Cycle 1 (28-day cycles): Days 1 and 15 (pre-dose and at multiple time points (up to 24 hours) post-dose; or Phase 2 Cycle 1 (28-day cycles): Days 15 or 22 pre-dose and at multiple time points (up to 24 hours) post-dose
measure: Time of Maximum Observed Plasma Concentration (tmax) of H3B-6545
time frame: Phase 1, Cycle 1 (28-day cycles): Days 1 and 15 pre-dose and at multiple time points (up to 24 hours) post-dose; or Phase 2 Cycle 1 (28-day cycles): Days 15 or 22 pre-dose and at multiple time points (up to 24 hours) post-dose
measure: Objective Response Rate (ORR)
time frame: Phase 1 and 2 up to approximately 36 months
measure: Duration of Response (DoR)
time frame: Phase 1 and 2 up to approximately 36 months
measure: Disease Control Rate (DCR)
time frame: Phase 1 and 2 up to approximately 36 months
measure: Clinical Benefit Rate (CBR)
time frame: Phase 1 and 2 up to approximately 36 months
measure: Progression-free survival (PFS)
time frame: Phase 1 and 2 up to approximately 36 months
measure: Overall Survival (OS)
time frame: Phase 1 and 2 up to approximately 36 months
arm group label: H3B-6545 Arm 1: Dose escalation
arm group type: Experimental
arm group label: H3B-6545 Arm 2: Phase 2
arm group type: Experimental
intervention type: Drug
intervention name: H3B-6545
description: Oral capsules by mouth once daily
arm group label: H3B-6545 Arm 1: Dose escalation
arm group label: H3B-6545 Arm 2: Phase 2
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
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country: France
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms