<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/NCT02248090</url>
  </required_header>
  <id_info>
    <org_study_id>D6090C00001</org_study_id>
    <nct_id>NCT02248090</nct_id>
  </id_info>
  <brief_title>AZD9496 First Time in Patients Ascending Dose Study</brief_title>
  <official_title>Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of Ascending Doses of AZD9496 in Women With Estrogen Receptor Positive HER-2 Negative Advanced Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AstraZeneca</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase 1 open label multicentre study of AZD9496 administered orally in patients&#xD;
      with advanced ER+ HER2 negative breast cancer. The study design allows an escalation of dose&#xD;
      with intensive safety monitoring to ensure the safety of patients. The study will determine&#xD;
      the maximum tolerated dose. In addition, expansion cohort(s) at potential therapeutic dose(s)&#xD;
      in patients with or without ESR1 mutations will be enrolled to further determine the safety,&#xD;
      tolerability, pharmacokinetics and biological activity of AZD9496&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics&#xD;
      and Preliminary Anti-tumour Activity of Ascending Doses of AZD9496 in Women with Estrogen&#xD;
      Receptor Positive HER-2 Negative Advanced Breast Cancer&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 22, 2014</start_date>
  <completion_date type="Actual">April 3, 2019</completion_date>
  <primary_completion_date type="Actual">January 31, 2017</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>Safety and tolerability</measure>
    <time_frame>Routine safety assessments, throughout the period that patients receive AZD9496 up to 28 days following discontinuation of last dose of study treatment.</time_frame>
    <description>Safety and tolerability in terms of adverse events, serious adverse events (including death) and safety measures: ECG, physical examination, vital signs and laboratory variables. Definition of maximum tolerated dose (MTD) or maximum feasible dose (MFD) by measuring the number of evaluable patients with dose-limiting toxicities.Time frame DLT period 28 days</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Single and multiple dose pharmacokinetics of AZD9496</measure>
    <time_frame>12 weeks</time_frame>
    <description>measurement of plasma levels of AZD9496 at pre-defined intervals in order to establish pharmacokinetic parameters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>4β-hydroxycholesterol concentration in blood</measure>
    <time_frame>12 weeks</time_frame>
    <description>Understanding of the CYP3A4 induction potential of AZD9496 by measuring 4β-hydroxycholesterol concentration in blood samples at pre-defined intervals</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antitumour activity</measure>
    <time_frame>every 8 weeks for 24 weeks and then every 12 weeks thereafter until disease progression</time_frame>
    <description>Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>ER+ HER2- Advanced Breast Cancer</condition>
  <arm_group>
    <arm_group_label>AZD9496</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AZD9496 dose escalation and expansion(s)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AZD9496</intervention_name>
    <description>AZD9496</description>
    <arm_group_label>AZD9496</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AZD9496</intervention_name>
    <description>If initial dosing of AZD9496 is tolerated then subsequent cohorts will test increasing doses until a maximum tolerated dose or maximum feasible dose is defined</description>
    <arm_group_label>AZD9496</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria: Provision of signed and dated, written informed consent prior to any&#xD;
        mandatory study specific procedures, sampling and analyses. Aged at least 18 years. Any&#xD;
        menopausal status. Pre- or peri-menopausal women must have commenced treatment with an LHRH&#xD;
        agonist at least 4 weeks prior to starting study treatment and must be willing to continue&#xD;
        to receive LHRH agonist therapy for the duration of the trial. Histological or cytological&#xD;
        confirmation of adenocarcinoma of the breast. ER-positive according to local laboratory;&#xD;
        HER-2 negative. Metastatic disease or locoregionally recurrent disease which is not&#xD;
        amenable to treatment with curative intent. Disease progression after at least 6 months of&#xD;
        endocrine therapy for ER+ breast cancer. Radiological or objective evidence of progression&#xD;
        on or after the last systemic therapy prior to starting study treatment. Receipt of ≤2&#xD;
        lines of prior chemotherapy for advanced disease. Females of child-bearing potential must&#xD;
        agree to use adequate contraceptive measures, must not be breast feeding and must have a&#xD;
        negative pregnancy test prior to start of dosing. Eastern Cooperative Oncology Group (ECOG)&#xD;
        performance status 0-1 with no deterioration over the previous 2 weeks and minimum life&#xD;
        expectancy of 12 weeks.&#xD;
&#xD;
        Exclusion Criteria: Any cytotoxic chemotherapy, investigational agents or other anti-cancer&#xD;
        drugs for the treatment of advanced breast cancer from a previous treatment regimen or&#xD;
        clinical study within 14 days of the first dose of study treatment. Any unresolved&#xD;
        toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events&#xD;
        (CTCAE) grade 1 at the time of starting study treatment with the exception of alopecia.&#xD;
        Presence of life-threatening metastatic visceral disease, uncontrolled central nervous&#xD;
        system metastatic disease or symptomatic pulmonary lymphangitic spread. Any evidence of&#xD;
        severe or uncontrolled systemic diseases, including uncontrolled hypertension, active&#xD;
        bleeding diatheses, or active infection. Unexplained symptomatic endometrial disorders.&#xD;
        Uncontrolled symptomatic thyroid dysfunction. Inadequate bone marrow reserve or organ&#xD;
        function&#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>Erika Hamilton</last_name>
    <role>Principal Investigator</role>
    <affiliation>Nashville Hospital, United States</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Justin Lindemann</last_name>
    <role>Study Director</role>
    <affiliation>AstraZeneca</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Florida Cancer Specialists</name>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <zip>34232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National Univ. Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>110-744</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Cambridge</city>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christie</name>
      <address>
        <city>Manchester</city>
        <zip>M20 4BX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>France</country>
  </removed_countries>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>September 22, 2014</study_first_submitted>
  <study_first_submitted_qc>September 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>June 21, 2019</last_update_submitted>
  <last_update_submitted_qc>June 21, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 24, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Phase 1</keyword>
  <keyword>Safety</keyword>
  <keyword>Tolerability</keyword>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Ascending Doses</keyword>
  <keyword>Estrogen Receptor Positive</keyword>
  <keyword>Her2 Negative</keyword>
  <keyword>Advanced Breast Cancer</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/NCT02248090
org study id: D6090C00001
nct id: NCT02248090
lead sponsor: 
has dmc: No
This is a phase 1 open label multicentre study of AZD9496 administered orally in patients
      with advanced ER+ HER2 negative breast cancer. The study design allows an escalation of dose
      with intensive safety monitoring to ensure the safety of patients. The study will determine
      the maximum tolerated dose. In addition, expansion cohort(s) at potential therapeutic dose(s)
      in patients with or without ESR1 mutations will be enrolled to further determine the safety,
      tolerability, pharmacokinetics and biological activity of AZD9496
A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics
      and Preliminary Anti-tumour Activity of Ascending Doses of AZD9496 in Women with Estrogen
      Receptor Positive HER-2 Negative Advanced Breast Cancer
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety and tolerability
time frame: Routine safety assessments, throughout the period that patients receive AZD9496 up to 28 days following discontinuation of last dose of study treatment.
description: Safety and tolerability in terms of adverse events, serious adverse events (including death) and safety measures: ECG, physical examination, vital signs and laboratory variables. Definition of maximum tolerated dose (MTD) or maximum feasible dose (MFD) by measuring the number of evaluable patients with dose-limiting toxicities.Time frame DLT period 28 days
measure: Single and multiple dose pharmacokinetics of AZD9496
time frame: 12 weeks
description: measurement of plasma levels of AZD9496 at pre-defined intervals in order to establish pharmacokinetic parameters
measure: 4β-hydroxycholesterol concentration in blood
time frame: 12 weeks
description: Understanding of the CYP3A4 induction potential of AZD9496 by measuring 4β-hydroxycholesterol concentration in blood samples at pre-defined intervals
measure: Antitumour activity
time frame: every 8 weeks for 24 weeks and then every 12 weeks thereafter until disease progression
description: Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)
arm group label: AZD9496
arm group type: Experimental
description: AZD9496 dose escalation and expansion(s)
intervention type: Drug
intervention name: AZD9496
description: AZD9496
arm group label: AZD9496
intervention type: Drug
intervention name: AZD9496
description: If initial dosing of AZD9496 is tolerated then subsequent cohorts will test increasing doses until a maximum tolerated dose or maximum feasible dose is defined
arm group label: AZD9496
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Erika Hamilton
role: Principal Investigator
affiliation: Nashville Hospital, United States
last name: Justin Lindemann
role: Study Director
affiliation: AstraZeneca
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Korea, Republic of
country: United Kingdom
country: United States
country: France
responsible party type: Sponsor
mesh term: Breast Neoplasms