<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/NCT02185937</url>
  </required_header>
  <id_info>
    <org_study_id>ABILITY</org_study_id>
    <nct_id>NCT02185937</nct_id>
  </id_info>
  <brief_title>Influence of an Acidic Beverage on the Imatinib Exposure After Major Gastrectomy</brief_title>
  <acronym>ABILITY</acronym>
  <official_title>Influence of an Acidic Beverage (Coca-Cola) on the Exposure to Imatinib (GLIvec) After Major gastrecTomY in Patients With Gastrointestinal Stromal Tumors (ABILITY)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Radboud University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Radboud University Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The most common sites for GIST to occur are the stomach (60-70%) and proximal small&#xD;
      intestines (20-25%). Therefore patients with GIST often have altered GI-tract due to tumor&#xD;
      resection or palliative surgery which might affect imatinib exposure. Indeed, Yoo et al.&#xD;
      showed that steady state imatinib trough levels in patients with advanced GISTs after major&#xD;
      gastrectomy are lower compared to patients with a previous wedge resection or without gastric&#xD;
      surgery. Patients that underwent major gastrectomy had an average imatinib plasma trough&#xD;
      levels below 1000 µg/L. This while imatinib trough levels above 1000 µg/L are correlated to&#xD;
      more beneficial treatment out-comes (longer Progression Free Survival).&#xD;
&#xD;
      Since imatinib easily and rapidly dissolves at pH 5.5 or less, a lack of gastric acid&#xD;
      secretion might be causing the decreased exposure in the patients that underwent major&#xD;
      gastrectomy.&#xD;
&#xD;
      Therefore the investigators would like to study if the exposure to imatinib in patients after&#xD;
      major gastrectomy can be improved by creating a more acidic environment for absorption&#xD;
      through combining imatinib intake with Coca-Cola.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    inclusion was too slow&#xD;
  </why_stopped>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">November 2016</completion_date>
  <primary_completion_date type="Actual">November 2016</primary_completion_date>
  <phase>Phase 1</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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>imatinib area under the curve</measure>
    <time_frame>day 7; predose - 10 hours after dosing</time_frame>
    <description>imatinib exposure assessed as area under the curve</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>number of adverse events</measure>
    <time_frame>2 weeks</time_frame>
    <description>number of adverse events will be reported and compared for both treatments</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Gastrointestinal Stromal Tumor</condition>
  <condition>Major Gastrectomy</condition>
  <arm_group>
    <arm_group_label>water</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>imatinib intake with water</description>
  </arm_group>
  <arm_group>
    <arm_group_label>cola</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>imatinib intake with cola</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>cola</intervention_name>
    <description>imatinib intake with coca-cola</description>
    <arm_group_label>cola</arm_group_label>
    <other_name>Coca-cola</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female patients ≥ 18 years of age&#xD;
&#xD;
          -  Patients with GIST, who previously underwent major gastrectomy&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1&#xD;
&#xD;
          -  Already selected to receive imatinib therapy in a dose of 400-800mg imatinib daily, as&#xD;
             judged by the treating physician and with respect for and in agreement with the&#xD;
             registration guidelines&#xD;
&#xD;
          -  Subject is able and willing to sign the Informed Consent Form prior to screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Concomitant administration of any anti-cancer therapies (e.g. chemo-therapy, other&#xD;
             targeted therapy, experimental drug, etc) other than imatinib&#xD;
&#xD;
          -  Concomitant use of medication which strongly inhibits or induces CYP3A4&#xD;
&#xD;
          -  Refractory nausea and vomiting, malabsorption with other causes than gastrectomy or&#xD;
             external biliary shunt that would preclude adequate absorption.&#xD;
&#xD;
          -  Unwillingness to use Coca-Cola&#xD;
&#xD;
          -  Unwillingness or inability to swallow whole tablets&#xD;
&#xD;
          -  Inability to comply with the requirements of the protocol&#xD;
&#xD;
          -  Inability to understand the nature and extent of the study and the procedures required&#xD;
&#xD;
          -  Participation in a drug study within 60 days prior to the first day of this study&#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>Nielka van Erp</last_name>
    <role>Principal Investigator</role>
    <affiliation>Radboud University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Radboudumc</name>
      <address>
        <city>Nijmegen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <results_reference>
    <citation>Lubberman FJE, Gelderblom H, Wilmer CM, Kweekel DM, Desar IME, Colbers A, Burger D, van der Graaf WTA, van Erp N. Does a glass of Coke boost the exposure to imatinib in gastrointestinal stromal tumour patients after gastrectomy? Br J Clin Pharmacol. 2017 Oct;83(10):2312-2314. doi: 10.1111/bcp.13333. Epub 2017 Jul 4. No abstract available.</citation>
    <PMID>28677263</PMID>
  </results_reference>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>July 7, 2014</study_first_submitted>
  <study_first_submitted_qc>July 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 10, 2014</study_first_posted>
  <last_update_submitted>December 4, 2020</last_update_submitted>
  <last_update_submitted_qc>December 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>imatinib</keyword>
  <keyword>gastrectomy</keyword>
  <keyword>gastrointestinal stromal tumor</keyword>
  <keyword>pharmacokinetics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gastrointestinal Stromal Tumors</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/NCT02185937
org study id: ABILITY
nct id: NCT02185937
lead sponsor: 
has dmc: No
The most common sites for GIST to occur are the stomach (60-70%) and proximal small
      intestines (20-25%). Therefore patients with GIST often have altered GI-tract due to tumor
      resection or palliative surgery which might affect imatinib exposure. Indeed, Yoo et al.
      showed that steady state imatinib trough levels in patients with advanced GISTs after major
      gastrectomy are lower compared to patients with a previous wedge resection or without gastric
      surgery. Patients that underwent major gastrectomy had an average imatinib plasma trough
      levels below 1000 µg/L. This while imatinib trough levels above 1000 µg/L are correlated to
      more beneficial treatment out-comes (longer Progression Free Survival).

      Since imatinib easily and rapidly dissolves at pH 5.5 or less, a lack of gastric acid
      secretion might be causing the decreased exposure in the patients that underwent major
      gastrectomy.

      Therefore the investigators would like to study if the exposure to imatinib in patients after
      major gastrectomy can be improved by creating a more acidic environment for absorption
      through combining imatinib intake with Coca-Cola.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: None (Open Label)
measure: imatinib area under the curve
time frame: day 7; predose - 10 hours after dosing
description: imatinib exposure assessed as area under the curve
measure: number of adverse events
time frame: 2 weeks
description: number of adverse events will be reported and compared for both treatments
arm group label: water
arm group type: No Intervention
description: imatinib intake with water
arm group label: cola
arm group type: Active Comparator
description: imatinib intake with cola
intervention type: Dietary Supplement
intervention name: cola
description: imatinib intake with coca-cola
arm group label: cola
other name: Coca-cola
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Nielka van Erp
role: Principal Investigator
affiliation: Radboud University Medical Center
facility: 
country: Netherlands
citation: Lubberman FJE, Gelderblom H, Wilmer CM, Kweekel DM, Desar IME, Colbers A, Burger D, van der Graaf WTA, van Erp N. Does a glass of Coke boost the exposure to imatinib in gastrointestinal stromal tumour patients after gastrectomy? Br J Clin Pharmacol. 2017 Oct;83(10):2312-2314. doi: 10.1111/bcp.13333. Epub 2017 Jul 4. No abstract available.
PMID: 28677263
responsible party type: Sponsor
mesh term: Gastrointestinal Stromal Tumors