<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/NCT03816839</url>
  </required_header>
  <id_info>
    <org_study_id>TED15954</org_study_id>
    <secondary_id>U1111-1217-2758</secondary_id>
    <nct_id>NCT03816839</nct_id>
  </id_info>
  <brief_title>Evaluation of Orally Administered Amcenestrant (SAR439859) in Japanese Postmenopausal Patients With Advanced Breast Cancer</brief_title>
  <acronym>AMEERA-2</acronym>
  <official_title>A Phase 1 Study for the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics Evaluation of SAR439859, Administered Orally as Monotherapy in Japanese Postmenopausal Women With Estrogen Receptor-Positive And Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer (AMEERA-2)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sanofi</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sanofi</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Primary Objective:&#xD;
&#xD;
      To assess the incidence rate of dose-limiting toxicity and to confirm the recommended dose as&#xD;
      well as the maximum tolerated dose of SAR439859 administered as monotherapy to Japanese&#xD;
      postmenopausal women with estrogen receptor positive and human epidermal growth factor&#xD;
      receptor 2-negative advanced breast cancer.&#xD;
&#xD;
      Secondary Objective:&#xD;
&#xD;
        -  To characterize the overall safety profile of SAR439859 administered as monotherapy.&#xD;
&#xD;
        -  To characterize the pharmacokinetic profile of SAR439859 administered as monotherapy.&#xD;
&#xD;
        -  To evaluate the antitumor activity of SAR439859 administered as monotherapy and the&#xD;
           clinical benefit rate (complete response, partial response and stable disease ≥ 24&#xD;
           weeks).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The duration of the study for an individual participant will include a period to assess&#xD;
      eligibility (screening period) of up to 4 weeks (28 days), a treatment period of at least 1&#xD;
      cycle (28 days) of study treatment, and an End of Treatment (EOT) visit at least 30 days (or&#xD;
      until the participant receives another anticancer therapy, whichever is earlier) following&#xD;
      the last administration of study treatment. Study treatment may continue until precluded by&#xD;
      unacceptable toxicity, disease progression, or upon participant's request.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 25, 2019</start_date>
  <completion_date type="Anticipated">November 30, 2023</completion_date>
  <primary_completion_date type="Actual">October 27, 2020</primary_completion_date>
  <phase>Phase 1</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>Investigational medicinal product (IMP)-related dose limiting toxicities (DLTs)</measure>
    <time_frame>Day 1 to Day 28</time_frame>
    <description>Incidence rate of study treatment-related DLTs at Cycle 1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety: Adverse Events (AEs)</measure>
    <time_frame>Up to 30 days after administration of study treatment</time_frame>
    <description>Number of adverse events related to study therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of Pharmacokinetic parameter of SAR439859: tlag</measure>
    <time_frame>Day 1 and Day 22 of Cycle 1 (28 days)</time_frame>
    <description>Lag time, interval between administration time and the sampling time preceding the first concentration above the lower limit of quantification</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of Pharmacokinetic parameter of SAR439859: tmax</measure>
    <time_frame>Day 1 and Day 22 of Cycle 1 (28 days)</time_frame>
    <description>First time to reach Cmax</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of Pharmacokinetic parameter of SAR439859: Cmax</measure>
    <time_frame>Day 1 and Day 22 of Cycle 1 (28 days)</time_frame>
    <description>Maximum concentration observed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of Pharmacokinetic parameter of SAR439859: AUC0-24h or AUC0-10h and/or AUC0-12h</measure>
    <time_frame>Day 1 and Day 22 of Cycle 1 (28 days)</time_frame>
    <description>Area under the plasma concentration versus time curve over the dosing interval (24 hours, 10 hours or 12 hours)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of Pharmacokinetic parameter of SAR439859: Ctrough</measure>
    <time_frame>Day 1, Day 8, Day 15 and Day 22 of Cycle 1 (28 days) and Day 1 of Cycle 2</time_frame>
    <description>Plasma concentration observed just before treatment administration during repeated dosing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of antitumor activity: Objective response rate (ORR)</measure>
    <time_frame>64 weeks</time_frame>
    <description>Objective response rate (ORR) as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of antitumor activity: Clinical benefit rate (CBR)</measure>
    <time_frame>64 weeks</time_frame>
    <description>Clinical benefit rate is (CR [complete response] +PR [partial response] +SD [stable disease] ≥24 weeks) as per RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of antitumor activity: Duration of response</measure>
    <time_frame>64 weeks</time_frame>
    <description>Response duration defined as the time from initial response to the first documented tumor progression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of antitumor activity: Non-progression rate</measure>
    <time_frame>64 weeks</time_frame>
    <description>Non-progression rate at 24 weeks (percentage of participants without progression at 24 weeks)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>SAR439859</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>administered orally once daily or twice daily as monotherapy in fasted or fed state</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Amcenestrant (SAR439859)</intervention_name>
    <description>Pharmaceutical form: Capsules&#xD;
Route of administration: Oral</description>
    <arm_group_label>SAR439859</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria :&#xD;
&#xD;
          -  Participants must be postmenopausal women.&#xD;
&#xD;
          -  Breast adenocarcinoma patients with locally advanced not amenable to radiation or&#xD;
             surgery, inoperable and/or metastatic disease.&#xD;
&#xD;
          -  Either the primary or any metastatic site must be positive for estrogen receptor (ER)&#xD;
             (&gt;1% staining by immunohistochemistry).&#xD;
&#xD;
          -  Either the primary tumor or any metastatic site must be human epidermal growth factor&#xD;
             receptor 2 non-overexpressing.&#xD;
&#xD;
          -  Patients with at least 6 months of prior endocrine therapy.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group Performance Status (ECOG) ≥2.&#xD;
&#xD;
          -  Significant concomitant illness that would adversely affect participation in the&#xD;
             study.&#xD;
&#xD;
          -  Patients with a life expectancy less than 3 months.&#xD;
&#xD;
          -  Patient not suitable for participation, whatever the reason.&#xD;
&#xD;
          -  Major surgery within 4 weeks prior to first study treatment administration.&#xD;
&#xD;
          -  Treatment with strong and moderate cytochrome P450 3A inhibitors/inducers.&#xD;
&#xD;
          -  Patients with known endometrial disorders, uterine bleeding or ovarian cysts.&#xD;
&#xD;
          -  Treatment with anticancer less than 2 weeks before first study treatment.&#xD;
&#xD;
          -  Prior treatment with selective estrogen receptor down (SERD)-regulator (except&#xD;
             fulvestrant for which a washout of at least 6 weeks is required).&#xD;
&#xD;
          -  Inadequate hematological function.&#xD;
&#xD;
          -  Inadequate renal function with serum creatinine ≥1.5 x upper limit of normal (ULN).&#xD;
&#xD;
          -  Liver function: aspartate aminotransferase &gt;3 x ULN, or alanine aminotransferase &gt;3 x&#xD;
             ULN. Total bilirubin &gt;1.5 x ULN.&#xD;
&#xD;
          -  Non-resolution of any prior treatment related toxicity to &lt;Grade 2, except for&#xD;
             alopecia&#xD;
&#xD;
        The above information is not intended to contain all considerations relevant to a patient's&#xD;
        potential participation in a clinical trial.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Sciences &amp; Operations</last_name>
    <role>Study Director</role>
    <affiliation>Sanofi</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Investigational Site Number 3920002</name>
      <address>
        <city>Chuo-Ku</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 3920001</name>
      <address>
        <city>Kashiwa-Shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 3920003</name>
      <address>
        <city>Nagoya-Shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>January 17, 2019</study_first_submitted>
  <study_first_submitted_qc>January 23, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 25, 2019</study_first_posted>
  <last_update_submitted>June 6, 2023</last_update_submitted>
  <last_update_submitted_qc>June 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </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>Yes</sharing_ipd>
    <ipd_description>Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org</ipd_description>
  </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/NCT03816839
org study id: TED15954
secondary id: U1111-1217-2758
nct id: NCT03816839
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Primary Objective:

      To assess the incidence rate of dose-limiting toxicity and to confirm the recommended dose as
      well as the maximum tolerated dose of SAR439859 administered as monotherapy to Japanese
      postmenopausal women with estrogen receptor positive and human epidermal growth factor
      receptor 2-negative advanced breast cancer.

      Secondary Objective:

        -  To characterize the overall safety profile of SAR439859 administered as monotherapy.

        -  To characterize the pharmacokinetic profile of SAR439859 administered as monotherapy.

        -  To evaluate the antitumor activity of SAR439859 administered as monotherapy and the
           clinical benefit rate (complete response, partial response and stable disease ≥ 24
           weeks).
The duration of the study for an individual participant will include a period to assess
      eligibility (screening period) of up to 4 weeks (28 days), a treatment period of at least 1
      cycle (28 days) of study treatment, and an End of Treatment (EOT) visit at least 30 days (or
      until the participant receives another anticancer therapy, whichever is earlier) following
      the last administration of study treatment. Study treatment may continue until precluded by
      unacceptable toxicity, disease progression, or upon participant's request.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Investigational medicinal product (IMP)-related dose limiting toxicities (DLTs)
time frame: Day 1 to Day 28
description: Incidence rate of study treatment-related DLTs at Cycle 1
measure: Safety: Adverse Events (AEs)
time frame: Up to 30 days after administration of study treatment
description: Number of adverse events related to study therapy
measure: Assessment of Pharmacokinetic parameter of SAR439859: tlag
time frame: Day 1 and Day 22 of Cycle 1 (28 days)
description: Lag time, interval between administration time and the sampling time preceding the first concentration above the lower limit of quantification
measure: Assessment of Pharmacokinetic parameter of SAR439859: tmax
time frame: Day 1 and Day 22 of Cycle 1 (28 days)
description: First time to reach Cmax
measure: Assessment of Pharmacokinetic parameter of SAR439859: Cmax
time frame: Day 1 and Day 22 of Cycle 1 (28 days)
description: Maximum concentration observed
measure: Assessment of Pharmacokinetic parameter of SAR439859: AUC0-24h or AUC0-10h and/or AUC0-12h
time frame: Day 1 and Day 22 of Cycle 1 (28 days)
description: Area under the plasma concentration versus time curve over the dosing interval (24 hours, 10 hours or 12 hours)
measure: Assessment of Pharmacokinetic parameter of SAR439859: Ctrough
time frame: Day 1, Day 8, Day 15 and Day 22 of Cycle 1 (28 days) and Day 1 of Cycle 2
description: Plasma concentration observed just before treatment administration during repeated dosing
measure: Assessment of antitumor activity: Objective response rate (ORR)
time frame: 64 weeks
description: Objective response rate (ORR) as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
measure: Assessment of antitumor activity: Clinical benefit rate (CBR)
time frame: 64 weeks
description: Clinical benefit rate is (CR [complete response] +PR [partial response] +SD [stable disease] ≥24 weeks) as per RECIST 1.1
measure: Assessment of antitumor activity: Duration of response
time frame: 64 weeks
description: Response duration defined as the time from initial response to the first documented tumor progression
measure: Assessment of antitumor activity: Non-progression rate
time frame: 64 weeks
description: Non-progression rate at 24 weeks (percentage of participants without progression at 24 weeks)
arm group label: SAR439859
arm group type: Experimental
description: administered orally once daily or twice daily as monotherapy in fasted or fed state
intervention type: Drug
intervention name: Amcenestrant (SAR439859)
description: Pharmaceutical form: Capsules
Route of administration: Oral
arm group label: SAR439859
criteria: 
gender: Female
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Sciences & Operations
role: Study Director
affiliation: Sanofi
facility: 
facility: 
facility: 
country: Japan
responsible party type: Sponsor
mesh term: Breast Neoplasms
sharing ipd: Yes
ipd description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org