<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/NCT01700270</url>
  </required_header>
  <id_info>
    <org_study_id>CTKI258A2120</org_study_id>
    <secondary_id>2012-001546-18</secondary_id>
    <nct_id>NCT01700270</nct_id>
  </id_info>
  <brief_title>Pharmacokinetic Drug-drug Interaction Study of Dovitinib (TKI258) in Patients With Advanced Solid Tumors.</brief_title>
  <acronym>CTKI258A2120</acronym>
  <official_title>A Phase I, Multi-center, Open-label, Drug-drug Interaction Study to Assess the Effect of the CYP1A2 Inhibitor, Fluvoxamine, on Dovitinib (TKI258) Pharmacokinetics in Patients With Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multi-center, open-label, single-sequence, crossover, drug-drug interaction (DDI)&#xD;
      study to assess the effect of the CYP1A2 inhibitor, fluvoxamine, on the PK of dovitinib in&#xD;
      patients with advanced solid tumors, excluding breast cancer. The purpose of this study is to&#xD;
      evaluate the effect of a CYP1A2 inhibitor, 100 mg fluvoxamine, on the PK of dovitinib when&#xD;
      administered at a dose of 300 mg on the dosing schedule, 5 days on/2 days off. The study will&#xD;
      consist of 2 phases: a Pharmacokinetic (PK) phase and a clinical treatment phase. The DDI&#xD;
      test will be conducted in the PK phase. The DDI test will assess the steady state PK profile&#xD;
      of dovitinib when administered alone and in the presence of the CYP1A2 inhibitor, fluvoxamine&#xD;
      (AUC 0-24h, AUC 0-72h and Cmax parameters). During the clinical treatment phase patients may&#xD;
      continue to receive treatment with TKI258 until disease progression (assessed by RECIST 1.1),&#xD;
      unacceptable toxicity, death or discontinuation from the study treatment for any other&#xD;
      reason.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>May 2013</start_date>
  <completion_date type="Actual">August 2014</completion_date>
  <primary_completion_date type="Actual">August 2014</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>TKI258 pharmacokinetics (PK) parameters: Cmax (Maximum (peak) concentration of drug)</measure>
    <time_frame>multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>TKI258 pharmacokinetics (PK) parameters: AUC 0-24 hr (Area Under the Curve)</measure>
    <time_frame>multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>TKI258 pharmacokinetics (PK) parameters: AUC 0-72 hr</measure>
    <time_frame>multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>TKI258 pharmacokinetics (PK) parameters: Tmax (Time to maximum concentration)</measure>
    <time_frame>multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>TKI258 pharmacokinetics (PK) parameters: T1/2 (Half-life time)</measure>
    <time_frame>multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>TKI258 pharmacokinetics (PK) parameters: CL/F (Apparent Oral Clearance)</measure>
    <time_frame>multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>TKI258 pharmacokinetics (PK) parameters: Vz/F (apparent volume of distribution)</measure>
    <time_frame>multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Frequency and severity of AEs (Adverse Events)</measure>
    <time_frame>up to at least 30 days after the last dose of dovitinib (TKI258)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency and severity of SAEs (Serious Adverse Events)</measure>
    <time_frame>up to at least 30 days after the last dose of dovitinib (TKI258)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Preliminary evidence of antitumor activity of dovitinib (TKI258)</measure>
    <time_frame>every 8 weeks until progression of disease</time_frame>
    <description>overall response based on investigator assessment and best overall response using RECIST 1.1</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Advanced Solid Tumors, Excluding Breast Cancer</condition>
  <arm_group>
    <arm_group_label>dovitinib (TKI258)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>dovitinib, 5 days on / 2 days off dose schedule</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>dovitinib (TKI258)</intervention_name>
    <arm_group_label>dovitinib (TKI258)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>fluvoxamine</intervention_name>
    <description>perpetrator drug; 7 days of dosing</description>
    <arm_group_label>dovitinib (TKI258)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients with a cytopathologically or histopathologically confirmed diagnosis of an&#xD;
        advanced solid tumor, excluding breast cancer which has progressed despite standard therapy&#xD;
        or for which no standard therapy exists - ECOG performance status 0 or 1 and an anticipated&#xD;
        life expectancy of ≥3 months- Patient must meet protocol-specific laboratory values&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        - Patients with brain metastases - Patients who have received or who are expected to&#xD;
        receive any prohibited medications and therapies - Patients who have received CYP1A2 or&#xD;
        CYP3A inhibitor medications within 5 days prior to start study treatment or are expected to&#xD;
        receive during the first 28 days after starting the study treatment - Patients who have&#xD;
        received CYP1A2 or CYP3A inducer medications within 30 days prior to start study treatment&#xD;
        or are expected to receive during the first 28 days after starting the study treatment -&#xD;
        Patients who are actively taking antidepressants, benzodiazepines, serotonergic drugs,&#xD;
        and/or monoamine oxidase inhibitors (MAOIs) - Patients who have not recovered from previous&#xD;
        anti-cancer therapies - Patient with impairment of gastrointestinal (GI) function or GI&#xD;
        disease that may significantly alter the absorption of TKI258 - Patients who have&#xD;
        concurrent severe and/or uncontrolled concomitant medical conditions that could compromise&#xD;
        participation in the study - Female patients who are pregnant or breast-feeding - Fertile&#xD;
        males or women not willing to use highly effective methods of contraception - Other&#xD;
        protocol-defined inclusion/exclusion criteria will apply&#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>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Montefiore Medical Center Montefiore Medical Center (SC)</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10467</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Therapy &amp; Research Center / UT Health Science Center SC</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Copenhagen</city>
        <zip>DK-2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Amsterdam</city>
        <zip>1066 CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Chur</city>
        <zip>7000</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Genève</city>
        <zip>1211</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
    <country>Netherlands</country>
    <country>Switzerland</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=13925</url>
    <description>Results for CTKI258A2120 on the Novartis Clinical Trial Website</description>
  </link>
  <verification_date>November 2014</verification_date>
  <study_first_submitted>October 2, 2012</study_first_submitted>
  <study_first_submitted_qc>October 2, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 4, 2012</study_first_posted>
  <last_update_submitted>December 17, 2020</last_update_submitted>
  <last_update_submitted_qc>December 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 21, 2020</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>Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluvoxamine</mesh_term>
  </intervention_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/NCT01700270
org study id: CTKI258A2120
secondary id: 2012-001546-18
nct id: NCT01700270
lead sponsor: 
has dmc: No
This is a multi-center, open-label, single-sequence, crossover, drug-drug interaction (DDI)
      study to assess the effect of the CYP1A2 inhibitor, fluvoxamine, on the PK of dovitinib in
      patients with advanced solid tumors, excluding breast cancer. The purpose of this study is to
      evaluate the effect of a CYP1A2 inhibitor, 100 mg fluvoxamine, on the PK of dovitinib when
      administered at a dose of 300 mg on the dosing schedule, 5 days on/2 days off. The study will
      consist of 2 phases: a Pharmacokinetic (PK) phase and a clinical treatment phase. The DDI
      test will be conducted in the PK phase. The DDI test will assess the steady state PK profile
      of dovitinib when administered alone and in the presence of the CYP1A2 inhibitor, fluvoxamine
      (AUC 0-24h, AUC 0-72h and Cmax parameters). During the clinical treatment phase patients may
      continue to receive treatment with TKI258 until disease progression (assessed by RECIST 1.1),
      unacceptable toxicity, death or discontinuation from the study treatment for any other
      reason.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: TKI258 pharmacokinetics (PK) parameters: Cmax (Maximum (peak) concentration of drug)
time frame: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
measure: TKI258 pharmacokinetics (PK) parameters: AUC 0-24 hr (Area Under the Curve)
time frame: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
measure: TKI258 pharmacokinetics (PK) parameters: AUC 0-72 hr
time frame: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
measure: TKI258 pharmacokinetics (PK) parameters: Tmax (Time to maximum concentration)
time frame: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
measure: TKI258 pharmacokinetics (PK) parameters: T1/2 (Half-life time)
time frame: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
measure: TKI258 pharmacokinetics (PK) parameters: CL/F (Apparent Oral Clearance)
time frame: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
measure: TKI258 pharmacokinetics (PK) parameters: Vz/F (apparent volume of distribution)
time frame: multiple time-points over 72h post dose on day Day 19 and Day 26 (PK phase)
measure: Frequency and severity of AEs (Adverse Events)
time frame: up to at least 30 days after the last dose of dovitinib (TKI258)
measure: Frequency and severity of SAEs (Serious Adverse Events)
time frame: up to at least 30 days after the last dose of dovitinib (TKI258)
measure: Preliminary evidence of antitumor activity of dovitinib (TKI258)
time frame: every 8 weeks until progression of disease
description: overall response based on investigator assessment and best overall response using RECIST 1.1
arm group label: dovitinib (TKI258)
arm group type: Experimental
description: dovitinib, 5 days on / 2 days off dose schedule
intervention type: Drug
intervention name: dovitinib (TKI258)
arm group label: dovitinib (TKI258)
intervention type: Drug
intervention name: fluvoxamine
description: perpetrator drug; 7 days of dosing
arm group label: dovitinib (TKI258)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Denmark
country: Netherlands
country: Switzerland
country: United States
url: https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=13925
description: Results for CTKI258A2120 on the Novartis Clinical Trial Website
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Fluvoxamine