<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/NCT04437017</url>
  </required_header>
  <id_info>
    <org_study_id>No.ZDWY[2020]LunziNo.(K01-1)</org_study_id>
    <nct_id>NCT04437017</nct_id>
  </id_info>
  <brief_title>Olanzapine or Dexamethasone, With 5-HT3 RA and NK-1 RA, to Prevent CINV</brief_title>
  <official_title>Olanzapine or Dexamethasone, With 5-HT3 RA and NK-1 RA, to Prevent Nausea and Vomiting Induced by Cisplatin-Based Doublet Chemotherapy: A Non-inferiority, Prospective, Multi-Centered, Randomized, Controlled, Phase III Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fifth Affiliated Hospital, Sun Yat-Sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fifth Affiliated Hospital, Sun Yat-Sen University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Chemotherapy-induced nausea and vomiting is a common side effect of cancer treatments, and&#xD;
      dexamethasone offers a clear advantage over placebo for protection against&#xD;
      chemotherapy-induced emesis in both acute and delayed phases. However, its side effects such&#xD;
      as moderate to severe insomnia, hyperglycemia, dyspepsia, upper abdominal discomfort,&#xD;
      irritability, increased appetite, weight gain and acne are gathering increasing concerns.&#xD;
      Several clinical trials have shown that olanzapine plays an important role in treating&#xD;
      delayed, refractory, breakthrough nausea and vomiting. Its side effects mainly include&#xD;
      sedation and weight gaining. At present, the NCCN guidelines have recommended&#xD;
      olanzapine-containing three-drug regimen for Highly Emetogenic Chemotherapy (HEC) and&#xD;
      moderate emetic chemotherapy (MEC) to prevent vomiting, but its data in the Chinese&#xD;
      population is limited. Hence, we initiated this prospective, multi-center, phase III study to&#xD;
      validate the dexamethasone-free protocol: applying olanzapine to prevent CINV instead of&#xD;
      dexamethasone.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 3, 2020</start_date>
  <completion_date type="Actual">July 1, 2022</completion_date>
  <primary_completion_date type="Actual">May 1, 2022</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>0-120h Complete Remission Rate</measure>
    <time_frame>24 hours ,48 hours, 72 hours, 96 hours, 120 hours after chemotherapy</time_frame>
    <description>The ratio of patients who have no vomiting and apply no anti-nausea drugs during the whole observation period.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>25-120 hours Complete Remission Rate</measure>
    <time_frame>24 hours , 48 hours, 72 hours, 96 hours, 120 hours after chemotherapy</time_frame>
    <description>The ratio of patients who have no vomiting and apply no anti-nausea drugs during the 25-120 hours observation period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>0-120h No Nausea Rate</measure>
    <time_frame>24 hours, 48 hours, 72 hours, 96 hours, 120 hours after chemotherapy</time_frame>
    <description>The ratio of patients who have no nausea during the whole observation period.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">557</enrollment>
  <condition>Chemotherapy-induced Nausea and Vomiting</condition>
  <arm_group>
    <arm_group_label>Olanzapine+NK-1 RA+5-HT3 RA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Using one of the 5-HT3 receptor antagonists (a. Palonosetron: 0.25 mg d1 intravenous; b. Granisetron: 1 mg d1 intravenously, or 2 mg d1 orally; c. Ondansetron: 8-16 mg d1 intravenous or oral. the specific agent is chosen by the primary clinician, and is only delivered on the first day) within 30 minutes before cisplatin. Using one of the NK-1 receptor antagonists(a. Aprepitant: 125 mg orally, d1, 80 mg orally, d2-3; b. Fosaprepitant: 150 mg intravenously, d1) within 1 hour before cisplatin. On day 1-4, Olanzapine (5mg) is delivered orally after dinner.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dexamethasone+NK-1 RA+5-HT3 RA</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Using one of the 5-HT3 receptor antagonists (a. Palonosetron: 0.25 mg d1 intravenous; b. Granisetron: 1 mg d1 intravenously, or 2 mg d1 orally; c. Ondansetron: 8-16 mg d1 intravenous or oral. the specific agent is chosen by the primary clinician, and is only delivered on the first day) within 30 minutes before cisplatin. Using one of the NK-1 receptor antagonists (a. Aprepitant: 125 mg orally, d1, 80 mg orally, d2-3; b. Fosaprepitant: 150 mg intravenously, d1) within 1 hour before cisplatin. On first day, dexamethasone (12 mg) is given orally/intravenously within 30 minutes before cisplatin administered, and on day 2-4, the given dose of dexamethasone is 8 mg.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Olanzapine+NK-1 RA+5-HT3 RA</intervention_name>
    <description>On day 1-4, Olanzapine (5mg) is delivered orally after dinner.</description>
    <arm_group_label>Olanzapine+NK-1 RA+5-HT3 RA</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone+NK-1 RA+5-HT3 RA</intervention_name>
    <description>On first day, dexamethasone (12 mg) is given orally/intravenously within 30 minutes before cisplatin administrated, and on day 2-4, the given dose of dexamethasone is 8 mg.</description>
    <arm_group_label>Dexamethasone+NK-1 RA+5-HT3 RA</arm_group_label>
    <other_name>Acidocont</other_name>
    <other_name>Deronil</other_name>
    <other_name>Dexacortal</other_name>
    <other_name>Desameton</other_name>
    <other_name>Fluprednisolone</other_name>
    <other_name>(11β，16α）-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4-diene-3,20-dione</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria (Patients are eligible to be included in the study only if they meet all&#xD;
        of the following criteria):&#xD;
&#xD;
          1. Cancer patients, age ≥ 18 years and ≤75 years, ECOG score 0-2 points, receiving&#xD;
             cisplatin-containing doublet chemotherapy such as cisplatin + gemcitabine / albumin&#xD;
             paclitaxel / etoposide /fluorouracil / irinotecan / temozolomide as first line&#xD;
             treatment;&#xD;
&#xD;
          2. Life expectancy ≥ 3 months;&#xD;
&#xD;
          3. Leucocytes≥3,000/uL;&#xD;
&#xD;
          4. AST≤2.5 × upper limit of normal;&#xD;
&#xD;
          5. Bilirubin ≤1.5 × upper limit of normal;&#xD;
&#xD;
          6. Serum creatinine ≤ 1.5 × upper limit of normal.&#xD;
&#xD;
        Exclusion Criteria (Patients will be excluded if any of the following criteria is met):&#xD;
&#xD;
          1. History of CNS disease, such as brain metastases or epilepsy;&#xD;
&#xD;
          2. Use of other antipsychotic drugs (such as risperidone, quetiapine, clozapine,&#xD;
             phenothiazine, or butyrophenone, or such treatment is under scheduling during the&#xD;
             study) within 30 days before enrollment; long-term use of phenothiazine as an&#xD;
             antipsychotic agent;&#xD;
&#xD;
          3. Concurrent use of pharyngeal or abdominal radiotherapy;&#xD;
&#xD;
          4. Concurrent use of quinolone antibiotics;&#xD;
&#xD;
          5. Chronic alcoholism;&#xD;
&#xD;
          6. Known hypersensitivity to olanzapine;&#xD;
&#xD;
          7. Know arrhythmia, uncontrolled congestive heart failure or acute myocardial infarction&#xD;
             within 6 months;&#xD;
&#xD;
          8. Known uncontrolled diabetes mellitus;&#xD;
&#xD;
          9. Vomiting or retching 24 hours before chemotherapy;&#xD;
&#xD;
         10. Use of anti-emesis drugs 48 hours before chemotherapy;&#xD;
&#xD;
         11. Concurrent use of amifostine;&#xD;
&#xD;
         12. Concurrent use of corticosteroids and the only anti-allergic choice is corticosteroids&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zhigang Liu, M.D.</last_name>
    <role>Study Director</role>
    <affiliation>Fifth Affilliated Hospital of Sun Yat-sen University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Zhigang Liu, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fifth Affilliated Hospital of Sun Yat-sen University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fifth Affilliated Hospital of Sun Yat-sen University</name>
      <address>
        <city>Zhuhai</city>
        <state>Guangdong</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>June 16, 2020</study_first_submitted>
  <study_first_submitted_qc>June 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 18, 2020</study_first_posted>
  <last_update_submitted>July 26, 2022</last_update_submitted>
  <last_update_submitted_qc>July 26, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 29, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fifth Affiliated Hospital, Sun Yat-Sen University</investigator_affiliation>
    <investigator_full_name>Zhigang Liu</investigator_full_name>
    <investigator_title>Vice Director</investigator_title>
  </responsible_party>
  <keyword>nausea</keyword>
  <keyword>vomiting</keyword>
  <keyword>antiemesis</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>Fluprednisolone</mesh_term>
    <mesh_term>Olanzapine</mesh_term>
    <mesh_term>Serotonin</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/NCT04437017
org study id: No.ZDWY[2020]LunziNo.(K01-1)
nct id: NCT04437017
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
is us export: No
Chemotherapy-induced nausea and vomiting is a common side effect of cancer treatments, and
      dexamethasone offers a clear advantage over placebo for protection against
      chemotherapy-induced emesis in both acute and delayed phases. However, its side effects such
      as moderate to severe insomnia, hyperglycemia, dyspepsia, upper abdominal discomfort,
      irritability, increased appetite, weight gain and acne are gathering increasing concerns.
      Several clinical trials have shown that olanzapine plays an important role in treating
      delayed, refractory, breakthrough nausea and vomiting. Its side effects mainly include
      sedation and weight gaining. At present, the NCCN guidelines have recommended
      olanzapine-containing three-drug regimen for Highly Emetogenic Chemotherapy (HEC) and
      moderate emetic chemotherapy (MEC) to prevent vomiting, but its data in the Chinese
      population is limited. Hence, we initiated this prospective, multi-center, phase III study to
      validate the dexamethasone-free protocol: applying olanzapine to prevent CINV instead of
      dexamethasone.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: 0-120h Complete Remission Rate
time frame: 24 hours ,48 hours, 72 hours, 96 hours, 120 hours after chemotherapy
description: The ratio of patients who have no vomiting and apply no anti-nausea drugs during the whole observation period.
measure: 25-120 hours Complete Remission Rate
time frame: 24 hours , 48 hours, 72 hours, 96 hours, 120 hours after chemotherapy
description: The ratio of patients who have no vomiting and apply no anti-nausea drugs during the 25-120 hours observation period.
measure: 0-120h No Nausea Rate
time frame: 24 hours, 48 hours, 72 hours, 96 hours, 120 hours after chemotherapy
description: The ratio of patients who have no nausea during the whole observation period.
arm group label: Olanzapine+NK-1 RA+5-HT3 RA
arm group type: Experimental
description: Using one of the 5-HT3 receptor antagonists (a. Palonosetron: 0.25 mg d1 intravenous; b. Granisetron: 1 mg d1 intravenously, or 2 mg d1 orally; c. Ondansetron: 8-16 mg d1 intravenous or oral. the specific agent is chosen by the primary clinician, and is only delivered on the first day) within 30 minutes before cisplatin. Using one of the NK-1 receptor antagonists(a. Aprepitant: 125 mg orally, d1, 80 mg orally, d2-3; b. Fosaprepitant: 150 mg intravenously, d1) within 1 hour before cisplatin. On day 1-4, Olanzapine (5mg) is delivered orally after dinner.
arm group label: Dexamethasone+NK-1 RA+5-HT3 RA
arm group type: Active Comparator
description: Using one of the 5-HT3 receptor antagonists (a. Palonosetron: 0.25 mg d1 intravenous; b. Granisetron: 1 mg d1 intravenously, or 2 mg d1 orally; c. Ondansetron: 8-16 mg d1 intravenous or oral. the specific agent is chosen by the primary clinician, and is only delivered on the first day) within 30 minutes before cisplatin. Using one of the NK-1 receptor antagonists (a. Aprepitant: 125 mg orally, d1, 80 mg orally, d2-3; b. Fosaprepitant: 150 mg intravenously, d1) within 1 hour before cisplatin. On first day, dexamethasone (12 mg) is given orally/intravenously within 30 minutes before cisplatin administered, and on day 2-4, the given dose of dexamethasone is 8 mg.
intervention type: Drug
intervention name: Olanzapine+NK-1 RA+5-HT3 RA
description: On day 1-4, Olanzapine (5mg) is delivered orally after dinner.
arm group label: Olanzapine+NK-1 RA+5-HT3 RA
intervention type: Drug
intervention name: Dexamethasone+NK-1 RA+5-HT3 RA
description: On first day, dexamethasone (12 mg) is given orally/intravenously within 30 minutes before cisplatin administrated, and on day 2-4, the given dose of dexamethasone is 8 mg.
arm group label: Dexamethasone+NK-1 RA+5-HT3 RA
other name: Acidocont
other name: Deronil
other name: Dexacortal
other name: Desameton
other name: Fluprednisolone
other name: (11β，16α）-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4-diene-3,20-dione
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Zhigang Liu, M.D.
role: Study Director
affiliation: Fifth Affilliated Hospital of Sun Yat-sen University
last name: Zhigang Liu, M.D.
role: Principal Investigator
affiliation: Fifth Affilliated Hospital of Sun Yat-sen University
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Fifth Affiliated Hospital, Sun Yat-Sen University
investigator full name: Zhigang Liu
investigator title: Vice Director
mesh term: Nausea
mesh term: Vomiting
mesh term: Dexamethasone
mesh term: Fluprednisolone
mesh term: Olanzapine
mesh term: Serotonin
sharing ipd: No