<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/NCT03817970</url>
  </required_header>
  <id_info>
    <org_study_id>18-1752.cc</org_study_id>
    <secondary_id>1R01GM123330-01A1</secondary_id>
    <nct_id>NCT03817970</nct_id>
  </id_info>
  <brief_title>Cisplatin Disposition and Kidney Injury</brief_title>
  <official_title>Drug Disposition and Nephrotoxicity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Memorial Sloan Kettering Cancer Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Rutgers University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of General Medical Sciences (NIGMS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Colorado, Denver</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is being done to determine 1) whether drugs to treat cisplatin-related nausea can&#xD;
      influence harm to the kidneys, 2) whether cisplatin levels in the body can influence the risk&#xD;
      of harm to the kidneys, and 3) whether a person's genetic make-up can increase or decrease&#xD;
      the likelihood of kidney injury due to cisplatin therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cisplatin (cis-diamminedichloroplatinum, Platinol®) is commonly utilized in chemotherapy&#xD;
      regimens for the treatment of solid cancers including lung, head and neck, and cervix. Its&#xD;
      main mechanism of action is through binding of DNA to form cross-links, leading to arrest of&#xD;
      DNA synthesis and replication. A major adverse consequence of cisplatin therapy is acute&#xD;
      kidney injury (AKI). It is reported that between 30 and 38 percent of patients develop signs&#xD;
      of nephrotoxicity (toxicity in the kidneys) after a single cisplatin dose, despite strategies&#xD;
      such as hydration to limit renal exposure. This is problematic for patients as kidney injury&#xD;
      can delay further treatment and limit the total number of chemotherapy cycles received,&#xD;
      thereby reducing the overall efficacy of cisplatin-containing regimens. Furthermore, it is&#xD;
      apparent that cisplatin will remain a central component to the treatment of solid tumors in&#xD;
      the foreseeable future. New approaches to identify patients at risk of acute kidney injury&#xD;
      (AKI) and prevent its development and progression are urgently needed. Cisplatin causes&#xD;
      nausea and vomiting, which requires treatment with 5-HT3 antagonists (5-HT3A) to control.&#xD;
      Associations between the clinical use of the 5-HT3A antiemetic drugs and the risk of&#xD;
      cisplatin AKI have recently been discovered. This study will interrogate relationships&#xD;
      between 5-HT3A drugs (granisetron, ondansetron, and palonosetron) and cisplatin AKI.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 26, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2023</primary_completion_date>
  <phase>N/A</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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Kidney Injury with Cisplatin and 5-HT3 Antagonist Antiemetic Regimen as Assessed by a 1.5 fold increase in a Biomarker Panel</measure>
    <time_frame>3 days</time_frame>
    <description>The effects of 5-HT3 antagonist antiemetic drugs on cisplatin kidney injury as indicated by a 1.5 fold increase in the urinary biomarker panel values at 3 days after treatment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The Effects of 5-HT3 Antagonist Antiemetic Drugs on Cisplatin Secretion</measure>
    <time_frame>3 days</time_frame>
    <description>The changes to cisplatin secretion in the urine (as an early biomarker for the detection of kidney injury) as indicated by a 6 mg difference between 5-HT3 Antagonist Antiemetic Drugs at 3 days after treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Targeted Genetic Polymorphisms are Associated with Risk of Kidney Injury Due to Cisplatin and 5-HT3 Antagonist Antiemetic Regimen as Assessed by a 1.5 fold increase in a Biomarker Panel</measure>
    <time_frame>3 days</time_frame>
    <description>The influence of targeted genetic polymorphisms on risk of kidney injury due to cisplatin and 5-HT3 Antagonist Antiemetic Drugs as indicated by a 1.5 fold increase in a urinary biomarker panel values at 3 days after treatment</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">72</enrollment>
  <condition>Nephrotoxicity</condition>
  <arm_group>
    <arm_group_label>Granisetron</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants randomized to an antiemetic regimen containing granisetron 2 mg oral or IV and evaluated for cisplatin toxicity after the first dose of cisplatin.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ondansetron</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants randomized to an antiemetic regimen containing ondansetron 8 mg oral or IV and evaluated for cisplatin toxicity after the first dose of cisplatin.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Palonosetron</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants randomized to an antiemetic regimen containing palonosetron 0.25 mg IV and evaluated for cisplatin toxicity after the first dose of cisplatin.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Granisetron</intervention_name>
    <description>An antiemetic regimen containing granisetron 2 mg oral or IV.</description>
    <arm_group_label>Granisetron</arm_group_label>
    <other_name>Kytril</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ondansetron</intervention_name>
    <description>An antiemetic regimen containing ondansetron 8 mg oral or IV.</description>
    <arm_group_label>Ondansetron</arm_group_label>
    <other_name>Zofran</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Palonosetron</intervention_name>
    <description>An antiemetic regimen containing palonosetron 0.25 mg IV.</description>
    <arm_group_label>Palonosetron</arm_group_label>
    <other_name>Aloxi</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female patient prescribed cisplatin at a dose of &gt;25 mg/m^2&#xD;
&#xD;
          -  Age 18-80 years&#xD;
&#xD;
          -  Hemoglobin &gt;/=10 g/dl&#xD;
&#xD;
          -  No consumption of grapefruit juice or alcohol within 7 days&#xD;
&#xD;
          -  No history of alcohol consumption of &gt;14 drinks/week&#xD;
&#xD;
          -  No history of organ transplantation or kidney dialysis&#xD;
&#xD;
          -  Willingness to comply with study&#xD;
&#xD;
          -  Not pregnant or lactating&#xD;
&#xD;
          -  No changes in chronic medications within 2 weeks&#xD;
&#xD;
          -  Estimated glomerular filtration rate (eGFR) &gt; 60 ml/min^2&#xD;
&#xD;
          -  Normal liver function (ALT and AST &lt;2x ULN)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of kidney cancer&#xD;
&#xD;
          -  Previous exposure to platinum-based chemotherapy&#xD;
&#xD;
          -  Herbal supplement use beyond marijuana&#xD;
&#xD;
          -  Exposure to other known nephrotoxins (including contrast agents) within the previous 2&#xD;
             weeks&#xD;
&#xD;
          -  Concurrent use of competitive inhibitors of transport proteins (metformin, cimetidine,&#xD;
             ranitidine, antiviral drugs, cephalosporins, topotecan, methotrexate, vinblastine)&#xD;
&#xD;
          -  Severe gastrointestinal disease with fluid losses&#xD;
&#xD;
          -  Diagnosis of a rapidly progressive glomerulonephritis&#xD;
&#xD;
          -  Allergy or contraindication to 5-HT3 Antagonists&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lauren Aleksunes, PharmD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rutgers University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Melanie Joy, PharmD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Colorado, Denver</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Melanie Joy, PharmD, PhD</last_name>
    <phone>303-724-7416</phone>
    <email>Melanie.Joy@ucdenver.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Cindy O'Bryant, PharmD</last_name>
    <phone>303-724-2625</phone>
    <email>Cindy.Obryant@ucdenver.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>UCHealth-Metro Denver</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Melanie Joy</last_name>
      <phone>919-819-6203</phone>
      <email>melanie.joy@cuanschutz.edu</email>
    </contact>
    <investigator>
      <last_name>Melanie Joy, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>George B, Joy MS, Aleksunes LM. Urinary protein biomarkers of kidney injury in patients receiving cisplatin chemotherapy. Exp Biol Med (Maywood). 2018 Feb;243(3):272-282. doi: 10.1177/1535370217745302. Epub 2017 Dec 12.</citation>
    <PMID>29231123</PMID>
  </reference>
  <reference>
    <citation>Chang C, Hu Y, Hogan SL, Mercke N, Gomez M, O'Bryant C, Bowles DW, George B, Wen X, Aleksunes LM, Joy MS. Pharmacogenomic Variants May Influence the Urinary Excretion of Novel Kidney Injury Biomarkers in Patients Receiving Cisplatin. Int J Mol Sci. 2017 Jun 22;18(7):1333. doi: 10.3390/ijms18071333.</citation>
    <PMID>28640195</PMID>
  </reference>
  <reference>
    <citation>George B, You D, Joy MS, Aleksunes LM. Xenobiotic transporters and kidney injury. Adv Drug Deliv Rev. 2017 Jul 1;116:73-91. doi: 10.1016/j.addr.2017.01.005. Epub 2017 Jan 20.</citation>
    <PMID>28111348</PMID>
  </reference>
  <reference>
    <citation>George B, Wen X, Mercke N, Gomez M, O'Bryant C, Bowles DW, Hu Y, Hogan SL, Joy MS, Aleksunes LM. Profiling of Kidney Injury Biomarkers in Patients Receiving Cisplatin: Time-dependent Changes in the Absence of Clinical Nephrotoxicity. Clin Pharmacol Ther. 2017 Apr;101(4):510-518. doi: 10.1002/cpt.606. Epub 2017 Feb 14.</citation>
    <PMID>28002630</PMID>
  </reference>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>November 27, 2018</study_first_submitted>
  <study_first_submitted_qc>January 22, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>October 31, 2022</last_update_submitted>
  <last_update_submitted_qc>October 31, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 1, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Nephrotoxicity</keyword>
  <keyword>Cisplatin</keyword>
  <keyword>Kidney Injury</keyword>
  <keyword>anti-emetics</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ondansetron</mesh_term>
    <mesh_term>Palonosetron</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/NCT03817970
org study id: 18-1752.cc
secondary id: 1R01GM123330-01A1
nct id: NCT03817970
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
is us export: Yes
This study is being done to determine 1) whether drugs to treat cisplatin-related nausea can
      influence harm to the kidneys, 2) whether cisplatin levels in the body can influence the risk
      of harm to the kidneys, and 3) whether a person's genetic make-up can increase or decrease
      the likelihood of kidney injury due to cisplatin therapy.
Cisplatin (cis-diamminedichloroplatinum, Platinol®) is commonly utilized in chemotherapy
      regimens for the treatment of solid cancers including lung, head and neck, and cervix. Its
      main mechanism of action is through binding of DNA to form cross-links, leading to arrest of
      DNA synthesis and replication. A major adverse consequence of cisplatin therapy is acute
      kidney injury (AKI). It is reported that between 30 and 38 percent of patients develop signs
      of nephrotoxicity (toxicity in the kidneys) after a single cisplatin dose, despite strategies
      such as hydration to limit renal exposure. This is problematic for patients as kidney injury
      can delay further treatment and limit the total number of chemotherapy cycles received,
      thereby reducing the overall efficacy of cisplatin-containing regimens. Furthermore, it is
      apparent that cisplatin will remain a central component to the treatment of solid tumors in
      the foreseeable future. New approaches to identify patients at risk of acute kidney injury
      (AKI) and prevent its development and progression are urgently needed. Cisplatin causes
      nausea and vomiting, which requires treatment with 5-HT3 antagonists (5-HT3A) to control.
      Associations between the clinical use of the 5-HT3A antiemetic drugs and the risk of
      cisplatin AKI have recently been discovered. This study will interrogate relationships
      between 5-HT3A drugs (granisetron, ondansetron, and palonosetron) and cisplatin AKI.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: Kidney Injury with Cisplatin and 5-HT3 Antagonist Antiemetic Regimen as Assessed by a 1.5 fold increase in a Biomarker Panel
time frame: 3 days
description: The effects of 5-HT3 antagonist antiemetic drugs on cisplatin kidney injury as indicated by a 1.5 fold increase in the urinary biomarker panel values at 3 days after treatment
measure: The Effects of 5-HT3 Antagonist Antiemetic Drugs on Cisplatin Secretion
time frame: 3 days
description: The changes to cisplatin secretion in the urine (as an early biomarker for the detection of kidney injury) as indicated by a 6 mg difference between 5-HT3 Antagonist Antiemetic Drugs at 3 days after treatment
measure: Targeted Genetic Polymorphisms are Associated with Risk of Kidney Injury Due to Cisplatin and 5-HT3 Antagonist Antiemetic Regimen as Assessed by a 1.5 fold increase in a Biomarker Panel
time frame: 3 days
description: The influence of targeted genetic polymorphisms on risk of kidney injury due to cisplatin and 5-HT3 Antagonist Antiemetic Drugs as indicated by a 1.5 fold increase in a urinary biomarker panel values at 3 days after treatment
arm group label: Granisetron
arm group type: Experimental
description: Participants randomized to an antiemetic regimen containing granisetron 2 mg oral or IV and evaluated for cisplatin toxicity after the first dose of cisplatin.
arm group label: Ondansetron
arm group type: Experimental
description: Participants randomized to an antiemetic regimen containing ondansetron 8 mg oral or IV and evaluated for cisplatin toxicity after the first dose of cisplatin.
arm group label: Palonosetron
arm group type: Experimental
description: Participants randomized to an antiemetic regimen containing palonosetron 0.25 mg IV and evaluated for cisplatin toxicity after the first dose of cisplatin.
intervention type: Drug
intervention name: Granisetron
description: An antiemetic regimen containing granisetron 2 mg oral or IV.
arm group label: Granisetron
other name: Kytril
intervention type: Drug
intervention name: Ondansetron
description: An antiemetic regimen containing ondansetron 8 mg oral or IV.
arm group label: Ondansetron
other name: Zofran
intervention type: Drug
intervention name: Palonosetron
description: An antiemetic regimen containing palonosetron 0.25 mg IV.
arm group label: Palonosetron
other name: Aloxi
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Lauren Aleksunes, PharmD, PhD
role: Principal Investigator
affiliation: Rutgers University
last name: Melanie Joy, PharmD, PhD
role: Principal Investigator
affiliation: University of Colorado, Denver
last name: Melanie Joy, PharmD, PhD
phone: 303-724-7416
email: Melanie.Joy@ucdenver.edu
last name: Cindy O'Bryant, PharmD
phone: 303-724-2625
email: Cindy.Obryant@ucdenver.edu
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
country: United States
citation: George B, Joy MS, Aleksunes LM. Urinary protein biomarkers of kidney injury in patients receiving cisplatin chemotherapy. Exp Biol Med (Maywood). 2018 Feb;243(3):272-282. doi: 10.1177/1535370217745302. Epub 2017 Dec 12.
PMID: 29231123
citation: Chang C, Hu Y, Hogan SL, Mercke N, Gomez M, O'Bryant C, Bowles DW, George B, Wen X, Aleksunes LM, Joy MS. Pharmacogenomic Variants May Influence the Urinary Excretion of Novel Kidney Injury Biomarkers in Patients Receiving Cisplatin. Int J Mol Sci. 2017 Jun 22;18(7):1333. doi: 10.3390/ijms18071333.
PMID: 28640195
citation: George B, You D, Joy MS, Aleksunes LM. Xenobiotic transporters and kidney injury. Adv Drug Deliv Rev. 2017 Jul 1;116:73-91. doi: 10.1016/j.addr.2017.01.005. Epub 2017 Jan 20.
PMID: 28111348
citation: George B, Wen X, Mercke N, Gomez M, O'Bryant C, Bowles DW, Hu Y, Hogan SL, Joy MS, Aleksunes LM. Profiling of Kidney Injury Biomarkers in Patients Receiving Cisplatin: Time-dependent Changes in the Absence of Clinical Nephrotoxicity. Clin Pharmacol Ther. 2017 Apr;101(4):510-518. doi: 10.1002/cpt.606. Epub 2017 Feb 14.
PMID: 28002630
responsible party type: Sponsor
mesh term: Ondansetron
mesh term: Palonosetron
mesh term: Granisetron
sharing ipd: No