<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/NCT02216149</url>
  </required_header>
  <id_info>
    <org_study_id>HUS-01/2013</org_study_id>
    <secondary_id>2013-003976-11</secondary_id>
    <nct_id>NCT02216149</nct_id>
  </id_info>
  <brief_title>Effects of S-1 and Capecitabine on Coronary Artery Blood Flow</brief_title>
  <acronym>FluoHeart</acronym>
  <official_title>Effects of S-1 and Capecitabine in Combination With Oxaliplatin on the Coronary Artery Blood Flow in Patients Metastatic Gastrointestinal Tract Adenocarcinoma: a Randomized Phase II Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Heikki Joensuu</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Helsinki University Central Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Fluoropyrimidine chemotherapy agents , such as 5-fluorouracil and capecitabine, are&#xD;
      occasionally associated with cardiac toxicity. Clinical fluoropyrimidine cardiotoxicity is&#xD;
      infrequent, but subclinical toxicity may be much more common. Cardiac toxicity may be less&#xD;
      frequent with S-1 as compared with 5-fluorouracil and capecitabine, but head-to-head&#xD;
      comparisons are lacking. The purpose of the study is to compare 2 measures of subclinical&#xD;
      coronary artery microvascular dysfunction, the coronary flow reserve and the coronary flow&#xD;
      response to a cold pressor test, in a patient population who are being treated for&#xD;
      adenocarcinoma of the gastrointestinal tract with one of 2 oxaliplatin-containing regimens,&#xD;
      either with oxaliplatin plus S-1 or with oxaliplatin plus capecitabine.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients diagnosed with adenocarcinoma of the gastroesophageal tract are randomly assigned to&#xD;
      receive two 3-weekly cycles of either XELOX (intravenous oxaliplatin 130 mg/m2 d.1 followed&#xD;
      by oral capecitabine 2000 mg/m2/day divided in 2 daily doses d1-14) or SOX (intravenous&#xD;
      oxaliplatin 130 mg/m2 d. 1 followed by oral S-1 25 mg/m2/day BID d1-14). A cross-over between&#xD;
      the 2 arms is carried out after the first 2 cycles; patients allocated to XELOX will receive&#xD;
      2 cycles of SOX (cycles 3 and 4), and those allocated to SOX will receive XELOX (cycles 3 and&#xD;
      4). Monitoring of the coronary artery flow, cardiac arrythmias, cardiac symptoms and blood&#xD;
      biochemistry is done at baseline, during each chemotherapy cycle (cycles 1 to 4) and after&#xD;
      treatment.Study treatment will continue until all patients have discontinued from treatment&#xD;
      or maximum 24 weeks from the date of the first day of treatment, whichever occurs first. At&#xD;
      that point, treatment may continue at the discretion of the Investigator. Each patient will&#xD;
      be followed for survival status for a minimum of 12 months after first dose of study&#xD;
      medication. Tumor assessments will be performed throughout the study period and analyzed&#xD;
      using Response Evaluation Criteria in Solid Tumors (RECIST) criteria (Version 1.1, 2009).&#xD;
      Computed tomography (CT) scans will be performed at the end of every 2 cycles. Cardiac&#xD;
      assessments will be performed and analyzed using non-invasive transthoracic Doppler&#xD;
      echocardiography, 24-h Holter registration, and plasma troponin concentration.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Slow accrual&#xD;
  </why_stopped>
  <start_date>January 2015</start_date>
  <completion_date type="Actual">August 2018</completion_date>
  <primary_completion_date type="Actual">August 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Frequency of coronary artery dysfunction</measure>
    <time_frame>3 months</time_frame>
    <description>The frequency of subclinical coronary artery dysfunction is as assessed by comparing the coronary flow reserve during chemotherapy with the baseline coronary flow reserve, and the coronary flow response to a cold pressor test.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Coronary artery blood flow rate</measure>
    <time_frame>3 months</time_frame>
    <description>The coronary artery blood flow rate is measured with ultrasound. The rates are compared with the baseline and between the groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac arrythmias during 24-hour electrocardiogram registration</measure>
    <time_frame>3 months</time_frame>
    <description>Cardiac arrythmias detected with Holter cardiac recording.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events between the allocation groups</measure>
    <time_frame>3 months</time_frame>
    <description>by CTCAE.4</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response to chemotherapy</measure>
    <time_frame>3 months</time_frame>
    <description>by RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival status</measure>
    <time_frame>12 months</time_frame>
    <description>Survival from the first dose of study medication to study completion</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Esophagus Cancer</condition>
  <condition>Stomach Cancer</condition>
  <condition>Small Bowel Cancer</condition>
  <condition>Colon Cancer</condition>
  <condition>Rectum Cancer</condition>
  <arm_group>
    <arm_group_label>S-1 plus oxaliplatin (SOX)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oxaliplatin 130 mg/m2 d. 1 followed by oral S-1 25 mg/m2/day BID d1-14.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Oxaliplatin plus capecitabine (XELOX)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intravenous oxaliplatin 130 mg/m2 d.1 followed by oral capecitabine 2000 mg/m2/day divided in 2 daily doses d1-14.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>S-1</intervention_name>
    <description>S-1 25 mg/m2/day BID d1-14, oxaliplatin injection 130 mg/m2 D1 every 3 weeks</description>
    <arm_group_label>S-1 plus oxaliplatin (SOX)</arm_group_label>
    <other_name>Teysuno</other_name>
    <other_name>tegafur/gimeracil/oteracil</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine</intervention_name>
    <description>capecitabine 2000 mg/m2/day divided in 2 daily doses d1-14, oxaliplatin injection 130 mg/m2 D1 every 3 weeks</description>
    <arm_group_label>Oxaliplatin plus capecitabine (XELOX)</arm_group_label>
    <other_name>Xeloda</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxaliplatin</intervention_name>
    <description>Oxaliplatin 130 mg/m2 D1 every 3 weeks</description>
    <arm_group_label>Oxaliplatin plus capecitabine (XELOX)</arm_group_label>
    <arm_group_label>S-1 plus oxaliplatin (SOX)</arm_group_label>
    <other_name>Eloxatin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Has given written informed consent.&#xD;
&#xD;
          -  Is at least 18 years of age.&#xD;
&#xD;
          -  Has advanced or metastatic gastrointestinal tract adenocarcinoma.&#xD;
&#xD;
          -  No previous cancer chemotherapy for cancer.&#xD;
&#xD;
          -  Measurable or evaluable lesions according to RECIST v1.1 criteria.&#xD;
&#xD;
          -  Is able to take medications orally.&#xD;
&#xD;
          -  Has ECOG performance status 0 or 1.&#xD;
&#xD;
          -  Has a life expectancy of at least 3 months.&#xD;
&#xD;
          -  Has adequate organ function.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Cancer considered operable without prior chemotherapy.&#xD;
&#xD;
          -  Prior chemotherapy to cancer.&#xD;
&#xD;
          -  Previous therapy with fluoropyrimidines or anthracyclines for any indication.&#xD;
&#xD;
          -  Inability to swallow tablets.&#xD;
&#xD;
          -  Known brain metastasis or leptomeningeal metastasis.&#xD;
&#xD;
          -  History of myocardial infarction, coronary stenting/graft.&#xD;
&#xD;
          -  History of unstable angina, coronary/peripheral artery bypass graft.&#xD;
&#xD;
          -  History of cerebrovascular accident or transient ischemic attack.&#xD;
&#xD;
          -  History of pulmonary embolism or deep vein thrombosis.&#xD;
&#xD;
          -  Symptomatic congestive heart failure.&#xD;
&#xD;
          -  Ongoing cardiac dysrhythmias.&#xD;
&#xD;
          -  Patients with any cardiac disease that requires regular medication.&#xD;
&#xD;
          -  Hypertensive crisis or severe hypertension that is not controlled.&#xD;
&#xD;
          -  Is a pregnant or lactating female.&#xD;
&#xD;
          -  The cardiac arterial flow tests cannot be done.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Heikki Joensuu, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Helsinki University Central Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Helsinki University Central Hospital</name>
      <address>
        <city>Helsinki</city>
        <zip>00029</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Finland</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>August 7, 2014</study_first_submitted>
  <study_first_submitted_qc>August 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2014</study_first_posted>
  <last_update_submitted>August 27, 2018</last_update_submitted>
  <last_update_submitted_qc>August 27, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 28, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Helsinki University Central Hospital</investigator_affiliation>
    <investigator_full_name>Heikki Joensuu</investigator_full_name>
    <investigator_title>MD, professor</investigator_title>
  </responsible_party>
  <keyword>fluoropyrimidine</keyword>
  <keyword>S-1</keyword>
  <keyword>Teysuno</keyword>
  <keyword>oxaliplatin</keyword>
  <keyword>coronary artery flow</keyword>
  <keyword>coronary artery dysfunction</keyword>
  <keyword>gastrointestinal tract cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stomach Neoplasms</mesh_term>
    <mesh_term>Esophageal Neoplasms</mesh_term>
    <mesh_term>Rectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Capecitabine</mesh_term>
    <mesh_term>Tegafur</mesh_term>
    <mesh_term>Oxaliplatin</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/NCT02216149
org study id: HUS-01/2013
secondary id: 2013-003976-11
nct id: NCT02216149
lead sponsor: 
has dmc: No
Fluoropyrimidine chemotherapy agents , such as 5-fluorouracil and capecitabine, are
      occasionally associated with cardiac toxicity. Clinical fluoropyrimidine cardiotoxicity is
      infrequent, but subclinical toxicity may be much more common. Cardiac toxicity may be less
      frequent with S-1 as compared with 5-fluorouracil and capecitabine, but head-to-head
      comparisons are lacking. The purpose of the study is to compare 2 measures of subclinical
      coronary artery microvascular dysfunction, the coronary flow reserve and the coronary flow
      response to a cold pressor test, in a patient population who are being treated for
      adenocarcinoma of the gastrointestinal tract with one of 2 oxaliplatin-containing regimens,
      either with oxaliplatin plus S-1 or with oxaliplatin plus capecitabine.
Patients diagnosed with adenocarcinoma of the gastroesophageal tract are randomly assigned to
      receive two 3-weekly cycles of either XELOX (intravenous oxaliplatin 130 mg/m2 d.1 followed
      by oral capecitabine 2000 mg/m2/day divided in 2 daily doses d1-14) or SOX (intravenous
      oxaliplatin 130 mg/m2 d. 1 followed by oral S-1 25 mg/m2/day BID d1-14). A cross-over between
      the 2 arms is carried out after the first 2 cycles; patients allocated to XELOX will receive
      2 cycles of SOX (cycles 3 and 4), and those allocated to SOX will receive XELOX (cycles 3 and
      4). Monitoring of the coronary artery flow, cardiac arrythmias, cardiac symptoms and blood
      biochemistry is done at baseline, during each chemotherapy cycle (cycles 1 to 4) and after
      treatment.Study treatment will continue until all patients have discontinued from treatment
      or maximum 24 weeks from the date of the first day of treatment, whichever occurs first. At
      that point, treatment may continue at the discretion of the Investigator. Each patient will
      be followed for survival status for a minimum of 12 months after first dose of study
      medication. Tumor assessments will be performed throughout the study period and analyzed
      using Response Evaluation Criteria in Solid Tumors (RECIST) criteria (Version 1.1, 2009).
      Computed tomography (CT) scans will be performed at the end of every 2 cycles. Cardiac
      assessments will be performed and analyzed using non-invasive transthoracic Doppler
      echocardiography, 24-h Holter registration, and plasma troponin concentration.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Frequency of coronary artery dysfunction
time frame: 3 months
description: The frequency of subclinical coronary artery dysfunction is as assessed by comparing the coronary flow reserve during chemotherapy with the baseline coronary flow reserve, and the coronary flow response to a cold pressor test.
measure: Coronary artery blood flow rate
time frame: 3 months
description: The coronary artery blood flow rate is measured with ultrasound. The rates are compared with the baseline and between the groups.
measure: Cardiac arrythmias during 24-hour electrocardiogram registration
time frame: 3 months
description: Cardiac arrythmias detected with Holter cardiac recording.
measure: Adverse events between the allocation groups
time frame: 3 months
description: by CTCAE.4
measure: Response to chemotherapy
time frame: 3 months
description: by RECIST 1.1
measure: Survival status
time frame: 12 months
description: Survival from the first dose of study medication to study completion
arm group label: S-1 plus oxaliplatin (SOX)
arm group type: Experimental
description: Oxaliplatin 130 mg/m2 d. 1 followed by oral S-1 25 mg/m2/day BID d1-14.
arm group label: Oxaliplatin plus capecitabine (XELOX)
arm group type: Active Comparator
description: Intravenous oxaliplatin 130 mg/m2 d.1 followed by oral capecitabine 2000 mg/m2/day divided in 2 daily doses d1-14.
intervention type: Drug
intervention name: S-1
description: S-1 25 mg/m2/day BID d1-14, oxaliplatin injection 130 mg/m2 D1 every 3 weeks
arm group label: S-1 plus oxaliplatin (SOX)
other name: Teysuno
other name: tegafur/gimeracil/oteracil
intervention type: Drug
intervention name: Capecitabine
description: capecitabine 2000 mg/m2/day divided in 2 daily doses d1-14, oxaliplatin injection 130 mg/m2 D1 every 3 weeks
arm group label: Oxaliplatin plus capecitabine (XELOX)
other name: Xeloda
intervention type: Drug
intervention name: Oxaliplatin
description: Oxaliplatin 130 mg/m2 D1 every 3 weeks
arm group label: Oxaliplatin plus capecitabine (XELOX)
arm group label: S-1 plus oxaliplatin (SOX)
other name: Eloxatin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
last name: Heikki Joensuu, MD
role: Principal Investigator
affiliation: Helsinki University Central Hospital
facility: 
country: Finland
responsible party type: Sponsor-Investigator
investigator affiliation: Helsinki University Central Hospital
investigator full name: Heikki Joensuu
investigator title: MD, professor
mesh term: Stomach Neoplasms
mesh term: Esophageal Neoplasms
mesh term: Rectal Neoplasms
mesh term: Capecitabine
mesh term: Tegafur
mesh term: Oxaliplatin