<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/NCT01728311</url>
  </required_header>
  <id_info>
    <org_study_id>15734</org_study_id>
    <nct_id>NCT01728311</nct_id>
  </id_info>
  <brief_title>Open Label Study of BAY1082439 in Patients With Advanced Cancer</brief_title>
  <official_title>An Open-label Phase I Dose-escalation Study to Characterize the Safety, Tolerability, Pharmacokinetics, and Maximum Tolerated Dose of BAY 1082439 Given Once Daily Continuously or in an Intermittent Dosing Schedule in Subjects With Advanced Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bayer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Bayer</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>
      The purpose of this study is to determine the safety, tolerability and the pharmacokinetics&#xD;
      of BAY1082439&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 21, 2012</start_date>
  <completion_date type="Actual">February 6, 2017</completion_date>
  <primary_completion_date type="Actual">June 3, 2016</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>Number of participants with adverse events as a measure of safety and tolerability</measure>
    <time_frame>Up to 2 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum tolerated dose of BAY1082439</measure>
    <time_frame>Up to 1 year</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum observed plasma concentration (Cmax) of BAY1082439 after a single dose</measure>
    <time_frame>Serial PK samples will be selected during cycle 1 day 1 (pre-dose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose) and sparse samples during the rest of the cycle as well as in cycle 2</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to Cmax (tmax) of BAY1082439 after a single dose</measure>
    <time_frame>Serial PK samples will be selected during cycle 1 day 1 (pre-dose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose) and sparse samples during the rest of the cycle as well as in cycle 2</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the plasma concentration-time curve (AUC[0-t]) of BAY1082439 after a single dose</measure>
    <time_frame>Serial PK samples will be selected during cycle 1 day 1 (pre-dose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose) and sparse samples during the rest of the cycle as well as in cycle 2</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve over the dosing interval (AUC[0-tau])</measure>
    <time_frame>PK parameters following single and repeat-dose administration in cycle 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum observed concentration (Cmax)</measure>
    <time_frame>PK parameters following single and repeat-dose administration in cycle 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of occurrence of Cmax (tmax)</measure>
    <time_frame>PK parameters following single and repeat-dose administration in cycle 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal phase half-life (t1/2)</measure>
    <time_frame>PK parameters following single and repeat-dose administration in cycle 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor response based on Response Evaluation Criteria in Solid Tumors, Version 1.1</measure>
    <time_frame>Up to 2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Neoplasms</condition>
  <arm_group>
    <arm_group_label>Arm 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BAY1082439</intervention_name>
    <description>BAY1082439 will be given orally once daily with a 21 days cycle. Dose will be started from 15mg.</description>
    <arm_group_label>Arm 1</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects with advanced, histologically or cytologically confirmed solid tumors,&#xD;
             refractory to any standard therapy, have no standard therapy available, or subjects&#xD;
             must have actively refused any treatment which would be regarded standard, and / or if&#xD;
             in the judgment of the investigator, experimental treatment is clinically and&#xD;
             ethically acceptable&#xD;
&#xD;
               -  Expansion phase only: Subjects with histologically or cytologically confirmed,&#xD;
                  locally advanced or metastatic endometrial cancer or breast cancer or iNHL, who&#xD;
                  are refractory to or have exhausted all available therapies&#xD;
&#xD;
          -  International normalized ratio (INR) and partial thromboplastin time (PTT) &lt;1.5 x ULN&#xD;
             [Subjects on anticoagulation with an agent such as coumadin or heparin will be allowed&#xD;
             to participate provided that no prior evidence of underlying abnormality in these&#xD;
             parameters exists.] For subjects on warfarin, close monitoring of at least weekly&#xD;
             evaluations will be performed until INR is stable based on a measurement at pre-dose,&#xD;
             as defined by the local standard of care&#xD;
&#xD;
          -  Measurable or evaluable disease&#xD;
&#xD;
          -  Life expectancy of at least 12 weeks&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2&#xD;
&#xD;
          -  Adequate bone marrow, liver and renal function&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of cardiac disease: congestive heart failure &gt; New York Heart Association&#xD;
             (NYHA) Class II, unstable angina (anginal symptoms at rest), new-onset angina (within&#xD;
             the past 3 months prior to the first dose of study drug), myocardial infarction within&#xD;
             the past 6 months prior to the first dose of study drug, or cardiac arrhythmias&#xD;
             requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)&#xD;
&#xD;
          -  Uncontrolled hypertension defined as systolic blood pressure &gt; 150 mmHg or diastolic&#xD;
             pressure &gt; 90 mmHg, despite optimal medical management&#xD;
&#xD;
          -  History of diabetes mellitus or gestational diabetes mellitus&#xD;
&#xD;
          -  Fasting blood glucose level &gt;125 mg/dL or HbA1c 7% at screening&#xD;
&#xD;
          -  Active clinically serious infections &gt; Grade 2&#xD;
&#xD;
          -  History of organ allograft&#xD;
&#xD;
          -  Seizure disorder requiring therapy (such as steroids or anti-epileptics)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bayer Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Bayer</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Seoul</city>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Seoul</city>
        <zip>120-752</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Singapore</city>
        <zip>119228</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Singapore</city>
        <zip>169610</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Taipei</city>
        <zip>10002</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
    <country>Singapore</country>
    <country>Taiwan</country>
  </location_countries>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>November 7, 2012</study_first_submitted>
  <study_first_submitted_qc>November 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 19, 2012</study_first_posted>
  <last_update_submitted>January 29, 2018</last_update_submitted>
  <last_update_submitted_qc>January 29, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 30, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <!-- 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/NCT01728311
org study id: 15734
nct id: NCT01728311
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to determine the safety, tolerability and the pharmacokinetics
      of BAY1082439
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with adverse events as a measure of safety and tolerability
time frame: Up to 2 years
measure: Maximum tolerated dose of BAY1082439
time frame: Up to 1 year
measure: Maximum observed plasma concentration (Cmax) of BAY1082439 after a single dose
time frame: Serial PK samples will be selected during cycle 1 day 1 (pre-dose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose) and sparse samples during the rest of the cycle as well as in cycle 2
measure: Time to Cmax (tmax) of BAY1082439 after a single dose
time frame: Serial PK samples will be selected during cycle 1 day 1 (pre-dose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose) and sparse samples during the rest of the cycle as well as in cycle 2
measure: Area under the plasma concentration-time curve (AUC[0-t]) of BAY1082439 after a single dose
time frame: Serial PK samples will be selected during cycle 1 day 1 (pre-dose and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose) and sparse samples during the rest of the cycle as well as in cycle 2
measure: Area under the concentration-time curve over the dosing interval (AUC[0-tau])
time frame: PK parameters following single and repeat-dose administration in cycle 1
measure: Maximum observed concentration (Cmax)
time frame: PK parameters following single and repeat-dose administration in cycle 1
measure: Time of occurrence of Cmax (tmax)
time frame: PK parameters following single and repeat-dose administration in cycle 1
measure: Terminal phase half-life (t1/2)
time frame: PK parameters following single and repeat-dose administration in cycle 1
measure: Tumor response based on Response Evaluation Criteria in Solid Tumors, Version 1.1
time frame: Up to 2 years
arm group label: Arm 1
arm group type: Experimental
intervention type: Drug
intervention name: BAY1082439
description: BAY1082439 will be given orally once daily with a 21 days cycle. Dose will be started from 15mg.
arm group label: Arm 1
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: No
last name: Bayer Study Director
role: Study Director
affiliation: Bayer
facility: 
facility: 
facility: 
facility: 
facility: 
country: Korea, Republic of
country: Singapore
country: Taiwan
country: United States
responsible party type: Sponsor