<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/NCT03017391</url>
  </required_header>
  <id_info>
    <org_study_id>CVS01</org_study_id>
    <nct_id>NCT03017391</nct_id>
  </id_info>
  <brief_title>Treatment Algorithm for Nausea and Vomiting in the Palliative Phase</brief_title>
  <official_title>Feasibility Study to Compare 2 Strategies of Treatment Algorithm for Treating Nausea and or Vomiting in the Palliative Phase of Cancer Care</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>
      Nausea and vomiting are frequently occurring problems in the palliative phase of patients&#xD;
      with cancer. Between 20-50% of them regularly suffer from nausea, retching or vomiting. Often&#xD;
      the cause of nausea and vomiting is multifactorial and symptomatic treatment is necessary.&#xD;
&#xD;
      Potential drugs for symptomatic anti-nausea therapy are metoclopramide, serotonin&#xD;
      antagonists, the combination of both and dexamethasone as rescue medication in case of&#xD;
      failure. There is no data that depicts which strategy is the best. This study will be&#xD;
      conducted to unravel which treatment algorithm is most successful.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Nausea and vomiting are frequently occurring problems in the palliative phase of patients&#xD;
      with cancer. Between 20-50% of them regularly suffer from nausea, retching or vomiting. Often&#xD;
      the cause of nausea and vomiting is multifactorial and symptomatic treatment is necessary.&#xD;
&#xD;
      Potential drugs for symptomatic anti-nausea therapy are metoclopramide, serotonin&#xD;
      antagonists, the combination of both and dexamethasone as rescue medication in case of&#xD;
      failure. There is no data that depicts which strategy is the best. This study will be&#xD;
      conducted to unravel which treatment algorithm is most successful: 1 to start with&#xD;
      metoclopramide, to add a serotonin antagonist (granisetron transdermal patch and 2 milligram&#xD;
      granisetron oral loading dose if the patient can swallow) in case of failure and to add&#xD;
      dexamethasone as rescue medication versus 2 an algorithm to start with a serotonin antagonist&#xD;
      (granisetron transdermal patch and 2 milligram granisetron oral loading dose if the patient&#xD;
      can swallow), to add metoclopramide in case of failure and to add dexamethasone as rescue&#xD;
      medication. Granisetron plaster is a new formulation of a well known serotonin antagonist and&#xD;
      might be useful especially within the patient group in the palliative phase.&#xD;
&#xD;
      The questions are:&#xD;
&#xD;
      Is it feasible to compare treatment algorithms for symptomatic treatment of nausea and&#xD;
      vomiting in palliative cancer patients? And is a stepwise symptomatic treatment algorithm to&#xD;
      manage nausea and vomiting using metoclopramide or granisetron transdermal patch as a start&#xD;
      medication effective in palliative patients in at least one of both treatment arms? Patients&#xD;
      will be asked to complete the QLQC30 and ESAS on different moments during the study. Besides,&#xD;
      they will be asked to complete a diary for nausea severity (NRS scale 0-10) and for the&#xD;
      frequency of vomiting and retching twice daily.&#xD;
&#xD;
      Success of a treatment algorithm is defined as nausea is &lt; 3 on NRS or a decrease of &gt;2 on&#xD;
      NRS for nausea combined with an absence of vomiting or retching in the last 3 days.&#xD;
      Incomplete success is defined as nausea of 3 on NRS during one occasion of the last 3 days&#xD;
      before the end of study but less than 4, no more than one retching a day during that period&#xD;
      and absence of vomiting. Complete failure is defined as nausea of 4 or more on an NRS during&#xD;
      the last 3 days or more than one retching daily or any vomiting or in case the patient has&#xD;
      stopped all medication due to side effects.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>January 2017</start_date>
  <primary_completion_date type="Anticipated">April 2018</primary_completion_date>
  <phase>Phase 4</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>NRS nausea</measure>
    <time_frame>15 days</time_frame>
    <description>response defined as NRS &lt;3 or decrease of more than 2 on NRS and absence of vomiting or retching in the last 3 days</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>days from T0 to control</measure>
    <time_frame>two weeks</time_frame>
    <description>The time from T0 until the moment that nausea and vomiting/retching is in control</description>
  </secondary_outcome>
  <other_outcome>
    <measure>feasibility</measure>
    <time_frame>6 months</time_frame>
    <description>number of included patients a 6 months period</description>
  </other_outcome>
  <other_outcome>
    <measure>comparison of starting metoclopramide to starting with granisetron</measure>
    <time_frame>6 months</time_frame>
    <description>response defined as NRS &lt;3 or decrease of more than 2 on NRS and absence of vomiting or retching in the last 3 days</description>
  </other_outcome>
  <other_outcome>
    <measure>quality of life</measure>
    <time_frame>15 days</time_frame>
    <description>QLQC30 scale</description>
  </other_outcome>
  <other_outcome>
    <measure>adverse events</measure>
    <time_frame>14/15 days</time_frame>
    <description>diary adverse events</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Nausea</condition>
  <condition>Vomiting</condition>
  <condition>Cancer</condition>
  <arm_group>
    <arm_group_label>algorithm 1 first metoclopramide</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>metoclopramide 10 mg tablets 3x daily orally and in those patients that cannot swallow tablets the medication will be substituted by suppositories 10 mg 3x daily rectally. In case of failure, granisetron patch 3.1mg/24 hours will be added to the treatment and a loading dose of 2 mg granisetron oral if the patient can swallow. In case of toxicity metoclopramide will be stopped. In case of failure of the combination (second step) or toxicity, an oral dose of dexamethasone 8 mg will be added daily.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>algorithm 2 first granisetron</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>granisetron patch 3.1 mg/24 hours will be offered to the patient, and a loading dose of 2 mg granisetron oral if the patient can swallow In case of failure, metoclopramide 10 mg tablets 3x daily orally will be added and in those patients that cannot swallow tablets the oral medication will be substituted with rectal suppositories 10 mg. The granisetron patch will only be withdrawn from patients that suffer from clinically relevant toxicity. Metoclopramide will then be administered.&#xD;
In the case of secondary failure or toxicity, dexamethasone 8 mg orally daily will be added.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>metoclopramide</intervention_name>
    <description>metoclopramide 10 mg tablets 3x daily orally or suppositories 10 mg 3x daily rectally, use until toxicity</description>
    <arm_group_label>algorithm 1 first metoclopramide</arm_group_label>
    <arm_group_label>algorithm 2 first granisetron</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>granisetron</intervention_name>
    <description>granisetron patch 3.1mg/24 hours, use until toxicity</description>
    <arm_group_label>algorithm 1 first metoclopramide</arm_group_label>
    <arm_group_label>algorithm 2 first granisetron</arm_group_label>
    <other_name>Sancuso</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>dexamethasone 8 mg, last step in both algorithms</description>
    <arm_group_label>algorithm 1 first metoclopramide</arm_group_label>
    <arm_group_label>algorithm 2 first granisetron</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Granisetron 2Mg Tablet</intervention_name>
    <description>granisetron 2 mg loading dose</description>
    <arm_group_label>algorithm 1 first metoclopramide</arm_group_label>
    <arm_group_label>algorithm 2 first granisetron</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patients 18 years or older in the palliative phase and&#xD;
&#xD;
          -  who suffer from nausea or vomiting with a rating on a numeric rating scale (NRS) of&#xD;
             more than 2 and&#xD;
&#xD;
          -  have a wish to be treated and&#xD;
&#xD;
          -  where no treatable cause is assignable&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients not able to sign informed consent.&#xD;
&#xD;
          -  Patients with known contra-indications for metoclopramide, 5HT-3 antagonists or&#xD;
             dexamethasone.&#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>C.A.H.H.V.M. Verhagen, M.D. Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Radboud University Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Christa v Schaik</last_name>
    <phone>024-3610353</phone>
    <email>christa.vanschaik@radboudumc.nl</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>C.A.H.H.V.M. Verhagen, M.D. Ph.D.</last_name>
    <phone>024-3610353</phone>
    <email>Stans.verhagen@radboudumc.nl</email>
  </overall_contact_backup>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>April 21, 2016</study_first_submitted>
  <study_first_submitted_qc>January 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 11, 2017</study_first_posted>
  <last_update_submitted>January 9, 2017</last_update_submitted>
  <last_update_submitted_qc>January 9, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 11, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>palliative care</keyword>
  <keyword>palliative medicine</keyword>
  <keyword>palliative</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nausea</mesh_term>
    <mesh_term>Vomiting</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Metoclopramide</mesh_term>
    <mesh_term>Granisetron</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03017391
org study id: CVS01
nct id: NCT03017391
lead sponsor: 
has dmc: No
Nausea and vomiting are frequently occurring problems in the palliative phase of patients
      with cancer. Between 20-50% of them regularly suffer from nausea, retching or vomiting. Often
      the cause of nausea and vomiting is multifactorial and symptomatic treatment is necessary.

      Potential drugs for symptomatic anti-nausea therapy are metoclopramide, serotonin
      antagonists, the combination of both and dexamethasone as rescue medication in case of
      failure. There is no data that depicts which strategy is the best. This study will be
      conducted to unravel which treatment algorithm is most successful.
Nausea and vomiting are frequently occurring problems in the palliative phase of patients
      with cancer. Between 20-50% of them regularly suffer from nausea, retching or vomiting. Often
      the cause of nausea and vomiting is multifactorial and symptomatic treatment is necessary.

      Potential drugs for symptomatic anti-nausea therapy are metoclopramide, serotonin
      antagonists, the combination of both and dexamethasone as rescue medication in case of
      failure. There is no data that depicts which strategy is the best. This study will be
      conducted to unravel which treatment algorithm is most successful: 1 to start with
      metoclopramide, to add a serotonin antagonist (granisetron transdermal patch and 2 milligram
      granisetron oral loading dose if the patient can swallow) in case of failure and to add
      dexamethasone as rescue medication versus 2 an algorithm to start with a serotonin antagonist
      (granisetron transdermal patch and 2 milligram granisetron oral loading dose if the patient
      can swallow), to add metoclopramide in case of failure and to add dexamethasone as rescue
      medication. Granisetron plaster is a new formulation of a well known serotonin antagonist and
      might be useful especially within the patient group in the palliative phase.

      The questions are:

      Is it feasible to compare treatment algorithms for symptomatic treatment of nausea and
      vomiting in palliative cancer patients? And is a stepwise symptomatic treatment algorithm to
      manage nausea and vomiting using metoclopramide or granisetron transdermal patch as a start
      medication effective in palliative patients in at least one of both treatment arms? Patients
      will be asked to complete the QLQC30 and ESAS on different moments during the study. Besides,
      they will be asked to complete a diary for nausea severity (NRS scale 0-10) and for the
      frequency of vomiting and retching twice daily.

      Success of a treatment algorithm is defined as nausea is < 3 on NRS or a decrease of >2 on
      NRS for nausea combined with an absence of vomiting or retching in the last 3 days.
      Incomplete success is defined as nausea of 3 on NRS during one occasion of the last 3 days
      before the end of study but less than 4, no more than one retching a day during that period
      and absence of vomiting. Complete failure is defined as nausea of 4 or more on an NRS during
      the last 3 days or more than one retching daily or any vomiting or in case the patient has
      stopped all medication due to side effects.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: NRS nausea
time frame: 15 days
description: response defined as NRS <3 or decrease of more than 2 on NRS and absence of vomiting or retching in the last 3 days
measure: days from T0 to control
time frame: two weeks
description: The time from T0 until the moment that nausea and vomiting/retching is in control
measure: feasibility
time frame: 6 months
description: number of included patients a 6 months period
measure: comparison of starting metoclopramide to starting with granisetron
time frame: 6 months
description: response defined as NRS <3 or decrease of more than 2 on NRS and absence of vomiting or retching in the last 3 days
measure: quality of life
time frame: 15 days
description: QLQC30 scale
measure: adverse events
time frame: 14/15 days
description: diary adverse events
arm group label: algorithm 1 first metoclopramide
arm group type: Active Comparator
description: metoclopramide 10 mg tablets 3x daily orally and in those patients that cannot swallow tablets the medication will be substituted by suppositories 10 mg 3x daily rectally. In case of failure, granisetron patch 3.1mg/24 hours will be added to the treatment and a loading dose of 2 mg granisetron oral if the patient can swallow. In case of toxicity metoclopramide will be stopped. In case of failure of the combination (second step) or toxicity, an oral dose of dexamethasone 8 mg will be added daily.
arm group label: algorithm 2 first granisetron
arm group type: Active Comparator
description: granisetron patch 3.1 mg/24 hours will be offered to the patient, and a loading dose of 2 mg granisetron oral if the patient can swallow In case of failure, metoclopramide 10 mg tablets 3x daily orally will be added and in those patients that cannot swallow tablets the oral medication will be substituted with rectal suppositories 10 mg. The granisetron patch will only be withdrawn from patients that suffer from clinically relevant toxicity. Metoclopramide will then be administered.
In the case of secondary failure or toxicity, dexamethasone 8 mg orally daily will be added.
intervention type: Drug
intervention name: metoclopramide
description: metoclopramide 10 mg tablets 3x daily orally or suppositories 10 mg 3x daily rectally, use until toxicity
arm group label: algorithm 1 first metoclopramide
arm group label: algorithm 2 first granisetron
intervention type: Drug
intervention name: granisetron
description: granisetron patch 3.1mg/24 hours, use until toxicity
arm group label: algorithm 1 first metoclopramide
arm group label: algorithm 2 first granisetron
other name: Sancuso
intervention type: Drug
intervention name: Dexamethasone
description: dexamethasone 8 mg, last step in both algorithms
arm group label: algorithm 1 first metoclopramide
arm group label: algorithm 2 first granisetron
intervention type: Drug
intervention name: Granisetron 2Mg Tablet
description: granisetron 2 mg loading dose
arm group label: algorithm 1 first metoclopramide
arm group label: algorithm 2 first granisetron
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: C.A.H.H.V.M. Verhagen, M.D. Ph.D.
role: Principal Investigator
affiliation: Radboud University Medical Center
last name: Christa v Schaik
phone: 024-3610353
email: christa.vanschaik@radboudumc.nl
last name: C.A.H.H.V.M. Verhagen, M.D. Ph.D.
phone: 024-3610353
email: Stans.verhagen@radboudumc.nl
responsible party type: Sponsor
mesh term: Nausea
mesh term: Vomiting
mesh term: Dexamethasone
mesh term: Metoclopramide
mesh term: Granisetron
sharing ipd: No