<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/NCT03040726</url>
  </required_header>
  <id_info>
    <org_study_id>2016-0843</org_study_id>
    <secondary_id>NCI-2017-00599</secondary_id>
    <secondary_id>2016-0843</secondary_id>
    <nct_id>NCT03040726</nct_id>
  </id_info>
  <brief_title>Netupitant and Palonosetron Hydrochloride in Preventing Chronic Nausea and Vomiting in Patients With Cancer</brief_title>
  <official_title>Fixed-Dose Netupitant and Palonosetron for Chronic Nausea and Vomiting in Cancer Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Helsinn Healthcare SA</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson Cancer Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This randomized phase II/III trial studies how well netupitant and palonosetron hydrochloride&#xD;
      works in preventing chronic nausea and vomiting in patients with cancer. Netupitant and&#xD;
      palonosetron hydrochloride may reduce nausea and vomiting.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To estimate the efficacy (i.e. change in nausea numeric rating scale [NRS] from baseline&#xD;
      between day 5-15) of fixed dose netupitant and palonosetron hydrochloride (palonosetron)&#xD;
      (NEPA) for chronic nausea in cancer patients.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To assess the secondary outcomes (e.g. proportion of patients who achieved their&#xD;
      personalized nausea goal, antiemetic use, nausea episodes duration/frequency) for NEPA versus&#xD;
      (vs.) placebo.&#xD;
&#xD;
      II. To assess the adverse effects associated with NEPA and placebo.&#xD;
&#xD;
      OUTLINE: Patients are randomized to 1 of 2 groups.&#xD;
&#xD;
      GROUP I: Patients receive netupitant orally (PO) and palonosetron hydrochloride PO on days 1,&#xD;
      6, and 11 in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      GROUP II: Patients receive placebo PO on days 1, 6, and 11.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 3, 2017</start_date>
  <completion_date type="Actual">February 14, 2022</completion_date>
  <primary_completion_date type="Actual">February 14, 2022</primary_completion_date>
  <phase>Phase 2/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>Supportive Care</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in nausea numeric rating scale</measure>
    <time_frame>Day 5-15</time_frame>
    <description>Descriptive statistics, including mean, standard deviation, 95% confidence intervals, median, range, frequency and percentage will be summarized. Will use a mixed model to examine the change in nausea overtime in both the netupitant and palonosetron hydrochloride arm and placebo arm. General linear model may be considered to examine the effect of potential important factors on nausea numeric rating scale.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients who achieved their personalized nausea goal</measure>
    <time_frame>Up to day 15</time_frame>
    <description>Descriptive statistics, including mean, standard deviation, 95% confidence intervals, median, range, frequency and percentage will be summarized.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antiemetic use</measure>
    <time_frame>Up to day 15</time_frame>
    <description>Descriptive statistics, including mean, standard deviation, 95% confidence intervals, median, range, frequency and percentage will be summarized.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nausea episodes duration/frequency</measure>
    <time_frame>Up to day 15</time_frame>
    <description>Descriptive statistics, including mean, standard deviation, 95% confidence intervals, median, range, frequency and percentage will be summarized.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>Up to day 15</time_frame>
    <description>Will be assessed by Common Terminology Criteria for Adverse Events. Will be collected and frequency will be summarized. Chi-squared test or Fisher's exact test, whichever the most appropriate, will be used to test for association between categorical variables, such as Common Terminology Criteria for Adverse Events adverse effects, between netupitant and palonosetron hydrochloride and placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global assessment</measure>
    <time_frame>Up to day 15</time_frame>
    <description>Chi-squared test or Fisher's exact test, whichever the most appropriate, will be used to test for association between categorical variables, such as global assessment, between netupitant and palonosetron hydrochloride and placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blinding</measure>
    <time_frame>Up to day 15</time_frame>
    <description>Chi-squared test or Fisher's exact test, whichever the most appropriate, will be used to test for association between categorical variables, such as blinding, between netupitant and palonosetron hydrochloride and placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Edmonton Symptom Assessment System</measure>
    <time_frame>Up to day 15</time_frame>
    <description>Wilcoxon rank sum test or Kruskal-Wallis test will be used to test for difference of continuous variables, such as Edmonton Symptom Assessment System between netupitant and palonosetron hydrochloride and placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional Living Index-Emesis questionnaire</measure>
    <time_frame>Up to day 15</time_frame>
    <description>Wilcoxon rank sum test or Kruskal-Wallis test will be used to test for difference of continuous variables, Functional Living Index-Emesis between netupitant and palonosetron hydrochloride and placebo.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Malignant Neoplasm</condition>
  <condition>Nausea</condition>
  <condition>Vomiting</condition>
  <arm_group>
    <arm_group_label>Group I (netupitant, palonosetron hydrochloride)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive netupitant orally (PO) and palonosetron hydrochloride PO on days 1, 6, and 11 in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group II (placebo)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients receive placebo PO on days 1, 6, and 11.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Netupitant</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Group I (netupitant, palonosetron hydrochloride)</arm_group_label>
    <other_name>CID6451149</other_name>
    <other_name>D05152</other_name>
    <other_name>RO 67-3189/000</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Palonosetron</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Group I (netupitant, palonosetron hydrochloride)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Palonosetron Hydrochloride</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Group I (netupitant, palonosetron hydrochloride)</arm_group_label>
    <other_name>Aloxi</other_name>
    <other_name>RS 25259-197</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Group II (placebo)</arm_group_label>
    <other_name>placebo therapy</other_name>
    <other_name>PLCB</other_name>
    <other_name>sham therapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Questionnaire Administration</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Group I (netupitant, palonosetron hydrochloride)</arm_group_label>
    <arm_group_label>Group II (placebo)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of cancer&#xD;
&#xD;
          -  Chronic nausea over the past 4 weeks&#xD;
&#xD;
          -  Average nausea numeric rating scale &gt;= 4/10 over the past 5 days at screening&#xD;
&#xD;
          -  Outpatient at MD Anderson Cancer Center&#xD;
&#xD;
          -  Karnofsky performance status &gt;= 50%&#xD;
&#xD;
          -  Age 18 or older&#xD;
&#xD;
          -  Able to complete study assessments, including keeping a daily diary&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Delirium (i.e. Memorial Delirium Rating Scale &gt; 13)&#xD;
&#xD;
          -  Clinical evidence of bowel obstruction at the time of study enrollment&#xD;
&#xD;
          -  Expected to use other 5HT3 antagonists or NK1 antagonists for prophylaxis during the&#xD;
             study&#xD;
&#xD;
          -  Continuation of over-the-counter therapies for nausea and/or vomiting during the study&#xD;
&#xD;
          -  On cytotoxic chemotherapy in the high/moderate/low emetogenic risk categories or oral&#xD;
             antineoplastic agents in the high or moderate emetogenic risk categories according to&#xD;
             the latest National Comprehensive Cancer Network (NCCN) guideline within 2 weeks of&#xD;
             study enrollment&#xD;
&#xD;
          -  On scheduled potent CYP3A4 inducers at the time of study enrollment (avasimibe,&#xD;
             carbamazepine, phenytoin, rifampin, efavirenz, nevirapine, barbiturates, systemic&#xD;
             glucocorticoids, modafinil, oxcarbazine, phenobarbital, pioglitazone, rifabutin, St.&#xD;
             John's wort, troglitazone)&#xD;
&#xD;
          -  On scheduled CYP3A4 substrates with narrow safety range at the time of study&#xD;
             enrollment (alfentanil, cyclosporine, dihydroergotamine, ergotamine, pimozide,&#xD;
             quinidine, sirolimus, tacrolimus)&#xD;
&#xD;
          -  On scheduled strong or moderate CYP3A4 inhibitors (boceprevir, clarithromycin,&#xD;
             conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil,&#xD;
             nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir,&#xD;
             telithromycin, voriconazole; amprenavir, aprepitant, atazanavir, ciprofloxacin,&#xD;
             darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit&#xD;
             juice, imatinib, verapamil) within one week of study enrollment&#xD;
&#xD;
          -  Unwilling to provide informed consent&#xD;
&#xD;
          -  Severe renal impairment (calculated creatinine clearance =&lt; 29 cc/min)&#xD;
&#xD;
               -  Calculated creatinine clearance can be done within 14 days of study enrollment&#xD;
&#xD;
          -  Severe liver impairment (Child-Pugh score &gt; 9)&#xD;
&#xD;
               -  Total (T.) bilirubin, albumin, prothrombin time, and serum creatinine tests can&#xD;
                  be done within 14 days of study enrollment (only if not performed in the last 14&#xD;
                  days)&#xD;
&#xD;
          -  Females who are pregnant, lactating, or intend to become pregnant during the&#xD;
             participation of the study; childbearing age women who are not on birth control;&#xD;
             positive pregnancy test for women of childbearing potential, as defined by intact&#xD;
             uterus and ovaries, and no history of menses within the last 12 months; pregnancy test&#xD;
             to be performed on the day of enrollment; in cases of women with elevated beta-human&#xD;
             chorionic gonadotropin (b-HCG), these candidates will be eligible to participate so&#xD;
             long as the level of b-HCG is not consistent with pregnancy and the non-pregnant&#xD;
             status is confirmed by a gynecologic examination&#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>David Hui</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>University of Texas MD Anderson Cancer Center Website</description>
  </link>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>January 31, 2017</study_first_submitted>
  <study_first_submitted_qc>February 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 2, 2017</study_first_posted>
  <last_update_submitted>March 4, 2022</last_update_submitted>
  <last_update_submitted_qc>March 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 7, 2022</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>
    <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>Palonosetron</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>February 7, 2023</submitted>
    <returned>March 7, 2023</returned>
    <submitted>April 17, 2023</submitted>
    <submission_canceled>April 20, 2023</submission_canceled>
    <submitted>April 20, 2023</submitted>
    <returned>May 15, 2023</returned>
    <submitted>September 7, 2023</submitted>
  </pending_results>
  <!-- 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/NCT03040726
org study id: 2016-0843
secondary id: NCI-2017-00599
secondary id: 2016-0843
nct id: NCT03040726
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This randomized phase II/III trial studies how well netupitant and palonosetron hydrochloride
      works in preventing chronic nausea and vomiting in patients with cancer. Netupitant and
      palonosetron hydrochloride may reduce nausea and vomiting.
PRIMARY OBJECTIVES:

      I. To estimate the efficacy (i.e. change in nausea numeric rating scale [NRS] from baseline
      between day 5-15) of fixed dose netupitant and palonosetron hydrochloride (palonosetron)
      (NEPA) for chronic nausea in cancer patients.

      SECONDARY OBJECTIVES:

      I. To assess the secondary outcomes (e.g. proportion of patients who achieved their
      personalized nausea goal, antiemetic use, nausea episodes duration/frequency) for NEPA versus
      (vs.) placebo.

      II. To assess the adverse effects associated with NEPA and placebo.

      OUTLINE: Patients are randomized to 1 of 2 groups.

      GROUP I: Patients receive netupitant orally (PO) and palonosetron hydrochloride PO on days 1,
      6, and 11 in the absence of disease progression or unacceptable toxicity.

      GROUP II: Patients receive placebo PO on days 1, 6, and 11.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Double (Participant, Investigator)
measure: Change in nausea numeric rating scale
time frame: Day 5-15
description: Descriptive statistics, including mean, standard deviation, 95% confidence intervals, median, range, frequency and percentage will be summarized. Will use a mixed model to examine the change in nausea overtime in both the netupitant and palonosetron hydrochloride arm and placebo arm. General linear model may be considered to examine the effect of potential important factors on nausea numeric rating scale.
measure: Proportion of patients who achieved their personalized nausea goal
time frame: Up to day 15
description: Descriptive statistics, including mean, standard deviation, 95% confidence intervals, median, range, frequency and percentage will be summarized.
measure: Antiemetic use
time frame: Up to day 15
description: Descriptive statistics, including mean, standard deviation, 95% confidence intervals, median, range, frequency and percentage will be summarized.
measure: Nausea episodes duration/frequency
time frame: Up to day 15
description: Descriptive statistics, including mean, standard deviation, 95% confidence intervals, median, range, frequency and percentage will be summarized.
measure: Incidence of adverse events
time frame: Up to day 15
description: Will be assessed by Common Terminology Criteria for Adverse Events. Will be collected and frequency will be summarized. Chi-squared test or Fisher's exact test, whichever the most appropriate, will be used to test for association between categorical variables, such as Common Terminology Criteria for Adverse Events adverse effects, between netupitant and palonosetron hydrochloride and placebo.
measure: Global assessment
time frame: Up to day 15
description: Chi-squared test or Fisher's exact test, whichever the most appropriate, will be used to test for association between categorical variables, such as global assessment, between netupitant and palonosetron hydrochloride and placebo.
measure: Blinding
time frame: Up to day 15
description: Chi-squared test or Fisher's exact test, whichever the most appropriate, will be used to test for association between categorical variables, such as blinding, between netupitant and palonosetron hydrochloride and placebo.
measure: Edmonton Symptom Assessment System
time frame: Up to day 15
description: Wilcoxon rank sum test or Kruskal-Wallis test will be used to test for difference of continuous variables, such as Edmonton Symptom Assessment System between netupitant and palonosetron hydrochloride and placebo.
measure: Functional Living Index-Emesis questionnaire
time frame: Up to day 15
description: Wilcoxon rank sum test or Kruskal-Wallis test will be used to test for difference of continuous variables, Functional Living Index-Emesis between netupitant and palonosetron hydrochloride and placebo.
arm group label: Group I (netupitant, palonosetron hydrochloride)
arm group type: Experimental
description: Patients receive netupitant orally (PO) and palonosetron hydrochloride PO on days 1, 6, and 11 in the absence of disease progression or unacceptable toxicity.
arm group label: Group II (placebo)
arm group type: Placebo Comparator
description: Patients receive placebo PO on days 1, 6, and 11.
intervention type: Drug
intervention name: Netupitant
description: Given PO
arm group label: Group I (netupitant, palonosetron hydrochloride)
other name: CID6451149
other name: D05152
other name: RO 67-3189/000
intervention type: Drug
intervention name: Palonosetron
description: Given PO
arm group label: Group I (netupitant, palonosetron hydrochloride)
intervention type: Drug
intervention name: Palonosetron Hydrochloride
description: Given PO
arm group label: Group I (netupitant, palonosetron hydrochloride)
other name: Aloxi
other name: RS 25259-197
intervention type: Other
intervention name: Placebo
description: Given PO
arm group label: Group II (placebo)
other name: placebo therapy
other name: PLCB
other name: sham therapy
intervention type: Other
intervention name: Questionnaire Administration
description: Ancillary studies
arm group label: Group I (netupitant, palonosetron hydrochloride)
arm group label: Group II (placebo)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: David Hui
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
facility: 
country: United States
url: http://www.mdanderson.org
description: University of Texas MD Anderson Cancer Center Website
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Nausea
mesh term: Vomiting
mesh term: Palonosetron
submitted: February 7, 2023
returned: March 7, 2023
submitted: April 17, 2023
submission canceled: April 20, 2023
submitted: April 20, 2023
returned: May 15, 2023
submitted: September 7, 2023