<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/NCT02264418</url>
  </required_header>
  <id_info>
    <org_study_id>3113001</org_study_id>
    <nct_id>NCT02264418</nct_id>
  </id_info>
  <brief_title>Safety and Tolerability of ODM-203 in Subjects With Advanced Solid Tumours</brief_title>
  <acronym>KIDES-203</acronym>
  <official_title>Safety and Tolerability of Single and Repeated Doses of ODM-203: An Open-label, Non-randomised, Uncontrolled, Dose Escalation, Multicentre, First-in-Human Study in Subjects With Advanced Solid Tumours</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Orion Corporation, Orion Pharma</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Orion Corporation, Orion Pharma</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this first-in-human study is to evaluate the safety and tolerability of&#xD;
      escalating doses of ODM-203 in subjects with advanced solid tumours and to determine the&#xD;
      maximum tolerated dose and dose limiting toxicities.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The safety profile of ODM-203 will be explored together with the pharmacokinetics,&#xD;
      pharmacodynamics and tumour response to treatment with ODM-203 to recommend the dosing&#xD;
      regimen for further clinical studies. The pharmacokinetic properties of ODM 203 will be&#xD;
      evaluated after single and multiple dose administrations at different dose levels&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 18, 2014</start_date>
  <completion_date type="Actual">May 2019</completion_date>
  <primary_completion_date type="Actual">May 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of adverse events</measure>
    <time_frame>From the date of informed consent to the date of the end of study visit estimated to be 6 months</time_frame>
    <description>Number of adverse event counts</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Frequency of responders to Response evaluation criteria in solid tumours (RECIST)</measure>
    <time_frame>Subjects will be followed for the duration of time in the study, expected to be an average of 6 months</time_frame>
    <description>The frequency of responders according to RECIST will be evaluated by dose level.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Eastern Cooperative Oncology Group (ECOG) Performance status</measure>
    <time_frame>Subjects will be followed for the duration of time in the study, expected to be an average of 6 months</time_frame>
    <description>The ECOG performance status and the change from baseline will be reported by dose level.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration curve (AUC)</measure>
    <time_frame>0 to 24hours post dose Day 1 and Day 15</time_frame>
    <description>Area under the plasma concentration curve (AUC) of ODM-203 will be measured to evaluate the relationship between ODM-203 dose, plasma exposure, pharmacodynamics and safety</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak plasma concentration (Cmax)</measure>
    <time_frame>After first dose administration to 24 hours Day 1 and Day 15</time_frame>
    <description>Peak plasma concentration (Cmax) of ODM-203 will be measured to evaluate the relationship between ODM-203 dose, plasma exposure, pharmacodynamics and safety</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">84</enrollment>
  <condition>Solid Tumours</condition>
  <arm_group>
    <arm_group_label>ODM 203</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral capsules given once daily dosage 50-800mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ODM-203</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral tablets given once daily 200-1600mg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ODM 203</intervention_name>
    <description>ODM 203</description>
    <arm_group_label>ODM 203</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ODM 203</intervention_name>
    <description>ODM 203</description>
    <arm_group_label>ODM 203</arm_group_label>
    <arm_group_label>ODM-203</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
          -  Male and female subjects over 18 years of age&#xD;
&#xD;
          -  Subjects with histologically or cytologically confirmed locally advanced or metastatic&#xD;
             tumours. Subjects in Part 2 to have a tumour/genetic aberration.&#xD;
&#xD;
          -  Availability of tumour sample for genetic analysis&#xD;
&#xD;
          -  Adequate haemopoietic, hepatic and renal function&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group performance status of 0 to 1&#xD;
&#xD;
          -  Serum mineral levels phosphate: 2.5 mg/dl; calcium: 8.8 mg/dl; magnesium: 1.2 mg/dl;&#xD;
             potassium: 11.7 mg/dl; sodium: 299mg/dl.&#xD;
&#xD;
          -  Recovery from reversible adverse events of previous systemic anti-cancer therapies to&#xD;
             baseline or grade 1 with the exception of alopecia;stable neuropathy of grade 2&#xD;
             induced by previous cancer treatment&#xD;
&#xD;
          -  Life expectancy of 12 weeks or more&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any prior anti VEGFR/FGFR treatment related AE that in the judgement of the&#xD;
             investigator is considered severe/life threatening&#xD;
&#xD;
          -  Subjects receiving warfarin&#xD;
&#xD;
          -  Active central nervous system metastases not controlled by prior surgery/radiotherapy&#xD;
             and/or low dose steroids for 4 weeks or more&#xD;
&#xD;
          -  Subjects with current evidence of endocrine alteration of calcium-phosphate&#xD;
             homeostasis&#xD;
&#xD;
          -  Concomitant therapies known to increase serum phosphorus and/or calcium levels that&#xD;
             cannot be discontinued or switched to a different therapy are not permitted within 14&#xD;
             days before the first dose of ODM-203.&#xD;
&#xD;
          -  Significant cardiovascular conditions/circumstances as follows:&#xD;
&#xD;
          -  a active or unstable cardio/cerebro-vascular disease&#xD;
&#xD;
          -  b Uncontrolled hypertension (systolic blood pressure ≥ 150mmHg and/or diastolic blood&#xD;
             pressure ≥ 90mg Hg with optimised antihypertensive therapy.&#xD;
&#xD;
          -  c history of severe arrhythmia, familial arrhythmia, conduction abnormality or&#xD;
             congenital long QT syndrome&#xD;
&#xD;
          -  dConcomitant therapies known to prolong the QT interval and associated with a risk of&#xD;
             Torsades de Pointes are not permitted within 7 days before the first dose of ODM 203&#xD;
&#xD;
          -  e Repeatable prolongation of QTcF interval ≥ 450 msec or any clinically significant&#xD;
             abnormality in the ECG at screening in 2 out of 3 recordings&#xD;
&#xD;
          -  f Left ventricular ejection fraction &lt;50% at screening&#xD;
&#xD;
          -  Subjects who received systemic anticancer treatment prior to the first dose of ODM-203&#xD;
             within the following timeframes: less than 28 days since the last dose of&#xD;
             antineoplastic therapy and/or 28 days of wide field radiotherapy or 14 days of limited&#xD;
             field radiation for palliation&#xD;
&#xD;
          -  Major surgery or serious infection within 21 days of the first dose of ODM-203&#xD;
&#xD;
          -  Known gastrointestinal disease or a procedure that may affect absorption of ODM 203&#xD;
&#xD;
          -  Serious concurrent medical condition or psychiatric illness&#xD;
&#xD;
          -  History and/or current evidence of ectopic mineralisation/calcification&#xD;
&#xD;
          -  Known active or past history of other primary malignancy&#xD;
&#xD;
          -  Female of child bearing potential&#xD;
&#xD;
          -  Female of child bearing potential or male subject with a female partner of child&#xD;
             bearing potential who does not agree to use effective contraception during the study&#xD;
             and for 3 months after the last dose of ODM 203&#xD;
&#xD;
          -  Known hypersensitivity to the study treatment excipients&#xD;
&#xD;
          -  Any condition which in the opinion of the investigator would impair the subject's&#xD;
             ability to comply with the study procedures&#xD;
&#xD;
          -  Participation in another interventional clinical trial/ concurrent treatment with any&#xD;
             investigational drug within 4 weeks prior to the start of treatment with ODM 203&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Petri Bono, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Helsinki University Central Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Finsen Centre</name>
      <address>
        <city>Copenhagen</city>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Helsinki University Central Hospital, Department of Oncology</name>
      <address>
        <city>Helsinki</city>
        <zip>00029</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Bergonie</name>
      <address>
        <city>Bordeaux</city>
        <zip>33000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gustave Roussy Oncology Institute</name>
      <address>
        <city>Villejuif</city>
        <zip>94805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>European Institute of Oncology</name>
      <address>
        <city>Milan</city>
        <zip>20141</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vall d'Hebron University Hospital</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah cannon Research Institute</name>
      <address>
        <city>London</city>
        <zip>W1G6AD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCL Cancer Institute</name>
      <address>
        <city>London</city>
        <zip>WC1E6DD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
    <country>Finland</country>
    <country>France</country>
    <country>Italy</country>
    <country>Spain</country>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>September 19, 2014</study_first_submitted>
  <study_first_submitted_qc>October 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2014</study_first_posted>
  <last_update_submitted>January 14, 2020</last_update_submitted>
  <last_update_submitted_qc>January 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Solid tumours</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>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/NCT02264418
org study id: 3113001
nct id: NCT02264418
lead sponsor: 
has dmc: Yes
The purpose of this first-in-human study is to evaluate the safety and tolerability of
      escalating doses of ODM-203 in subjects with advanced solid tumours and to determine the
      maximum tolerated dose and dose limiting toxicities.
The safety profile of ODM-203 will be explored together with the pharmacokinetics,
      pharmacodynamics and tumour response to treatment with ODM-203 to recommend the dosing
      regimen for further clinical studies. The pharmacokinetic properties of ODM 203 will be
      evaluated after single and multiple dose administrations at different dose levels
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Number of adverse events
time frame: From the date of informed consent to the date of the end of study visit estimated to be 6 months
description: Number of adverse event counts
measure: Frequency of responders to Response evaluation criteria in solid tumours (RECIST)
time frame: Subjects will be followed for the duration of time in the study, expected to be an average of 6 months
description: The frequency of responders according to RECIST will be evaluated by dose level.
measure: Eastern Cooperative Oncology Group (ECOG) Performance status
time frame: Subjects will be followed for the duration of time in the study, expected to be an average of 6 months
description: The ECOG performance status and the change from baseline will be reported by dose level.
measure: Area under the plasma concentration curve (AUC)
time frame: 0 to 24hours post dose Day 1 and Day 15
description: Area under the plasma concentration curve (AUC) of ODM-203 will be measured to evaluate the relationship between ODM-203 dose, plasma exposure, pharmacodynamics and safety
measure: Peak plasma concentration (Cmax)
time frame: After first dose administration to 24 hours Day 1 and Day 15
description: Peak plasma concentration (Cmax) of ODM-203 will be measured to evaluate the relationship between ODM-203 dose, plasma exposure, pharmacodynamics and safety
arm group label: ODM 203
arm group type: Experimental
description: Oral capsules given once daily dosage 50-800mg
arm group label: ODM-203
arm group type: Experimental
description: Oral tablets given once daily 200-1600mg
intervention type: Drug
intervention name: ODM 203
description: ODM 203
arm group label: ODM 203
intervention type: Drug
intervention name: ODM 203
description: ODM 203
arm group label: ODM 203
arm group label: ODM-203
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Petri Bono, MD
role: Principal Investigator
affiliation: Helsinki University Central Hospital
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Denmark
country: Finland
country: France
country: Italy
country: Spain
country: United Kingdom
responsible party type: Sponsor
mesh term: Neoplasms