<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/NCT04442516</url>
  </required_header>
  <id_info>
    <org_study_id>CisP Metabolomics</org_study_id>
    <nct_id>NCT04442516</nct_id>
  </id_info>
  <brief_title>Cisplatin Induced Kidney Toxicity</brief_title>
  <acronym>ACCENT</acronym>
  <official_title>A Canadian Study of Cisplatin mEtabolomics and NephroToxicity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Hospital for Sick Children</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Canadian Institutes of Health Research (CIHR)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>London Health Sciences Centre</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Provincial Health Services Authority</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The Hospital for Sick Children</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Cisplatin (CisP) is a chemotherapeutic agent used to treat head and neck and lung cancer in&#xD;
      adults and over 15 different pediatric cancers. Despite its known toxicity, CisP is still&#xD;
      widely used as a first line chemotherapy as it is so effective. Nephrotoxicity is one of the&#xD;
      most common adverse effects of CisP, occurring in 20-50% of patients. It manifests as acute&#xD;
      kidney injury (AKI) typically within the first few days of exposure and is associated with&#xD;
      short and long-term morbidity. Furthermore, AKI diagnosis is only possible once kidney damage&#xD;
      has progressed to functional impairment, when mitigation strategies are ineffective. Tests&#xD;
      that could predict AKI risk pre-emptively or diagnose early-stage AKI before functional loss&#xD;
      would be very impactful, affording opportunities for prevention or early intervention to&#xD;
      mitigate CisP nephrotoxicity, reduce morbidity and improve health outcomes.&#xD;
&#xD;
      The field of metabolomics seeks to identify patterns of small molecules (metabolites)&#xD;
      involved in cell or tissue metabolism related to disease states, or patient factors like&#xD;
      lifestyle and genetics. Plasma and urine are ideal for sampling the metabolome, which can&#xD;
      identify at-risk patients and reveal disease-related changes earlier than existing diagnostic&#xD;
      methods do.&#xD;
&#xD;
      In CisP-treated children and adults from across Canada, we will identify urine and plasma&#xD;
      metabolite profiles a) prior to CisP dosing that predict CisP AKI risk, and b) shortly after&#xD;
      dosing to identify early-stage nephrotoxicity, before clinical signs of AKI are detectable.&#xD;
      Our identified biomarkers will allow individualization of CisP treatment based on the level&#xD;
      of nephrotoxicity risk and the design of trials to mitigate the progression and complications&#xD;
      of CisP nephrotoxicity.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 12, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2028</completion_date>
  <primary_completion_date type="Anticipated">April 1, 2026</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>To identify patterns of metabolites and specific metabolites prior to and shortly after CisP treatment that predict AKI risk and identify the onset of AKI early (discovery cohort).</measure>
    <time_frame>8+ years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>To independently validate our findings and develop a precision medicine algorithm using metabolites to predict patients at high risk for developing CisP AKI (validation cohort).</measure>
    <time_frame>8+ years</time_frame>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">600</enrollment>
  <condition>Acute Kidney Injury</condition>
  <condition>Cancer</condition>
  <arm_group>
    <arm_group_label>Adults receiving Cisplatin as part of their cancer therapy</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Children receiving Cisplatin as part of their cancer therapy</arm_group_label>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Questionnaire, sampling of blood, urine and saliva</intervention_name>
    <description>We are following patients who are receiving Cisplatin as part of their cancer therapy.</description>
    <arm_group_label>Adults receiving Cisplatin as part of their cancer therapy</arm_group_label>
    <arm_group_label>Children receiving Cisplatin as part of their cancer therapy</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Urinary and plasma metabolites and saliva or blood sample for DNA.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Child Cohort. We already performed these study procedures on 159 children in the &quot;ABLE&quot;&#xD;
        study, a 12-centre cohort study.Eligibility criteria and data/samples collected on these&#xD;
        patients during their initial CisP treatment are almost identical to the present study. The&#xD;
        cohort diagnoses include neuroblastoma, medulloblastoma, osteosarcoma, germ cell tumour,&#xD;
        hepatoblastoma, and other cancers. Data and specimens from the pediatric study subjects in&#xD;
        the ABLE study who were recruited during their first CisP infusion (about half) will be&#xD;
        included in the current study. The remaining children (to reach a target of 300) will be&#xD;
        recruited over 3 years from the following centres: McGill, UBC, SickKids, U. Manitoba and&#xD;
        UWO. Adult Cohort. 300 adults (18 years of age or older) initiating CisP (≥75 mg/m2)&#xD;
        treatment for head/neck or lung cancers will be recruited to participate in this study from&#xD;
        PMH (Toronto), UBC and UWO over 2 years. Over 500 new patients/year are available across&#xD;
        all sites.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult participants: Initiating treatment with CisP (≥75 mg/m2) for head/neck or lung&#xD;
             cancers at one of the Adult participating sites; 18 years of age or older.&#xD;
&#xD;
          -  Paediatric participants: Initiating treatment with CisP for any cancer diagnosis at&#xD;
             one of the Pediatric participating sites; greater than 3 months of age.&#xD;
&#xD;
          -  All participants: Consent to participate in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of chronic kidney disease (CKD) at baseline (glomerular filtration rate &lt;60&#xD;
             mL/min/1.73m2, determined by chart review of either formal glomerular filtration rate&#xD;
             testing, 24 hour creatinine creatinine clearance of age-appropriate serum&#xD;
             creatinine-based estimated glomerular filtration rate equations; past kidney&#xD;
             transplant)&#xD;
&#xD;
          -  Previous use of any nephrotoxic drugs included on the provided Excluded Nephrotoxic&#xD;
             Medications list in the two weeks prior to initiation of CisP treatment&#xD;
&#xD;
          -  Previous use of CisP&#xD;
&#xD;
          -  Previous radiotherapy (total body irradiation or abdominal radiation only) in the last&#xD;
             1 month prior to study&#xD;
&#xD;
          -  Previous hematopoietic stem cell transplant&#xD;
&#xD;
          -  Any chronic or acute health condition that the investigator feels would render the&#xD;
             patient inappropriate for this study, including but not limited to significant&#xD;
             uncontrolled cardiorespiratory, hepatic, infectious, or renal disease at the&#xD;
             discretion of the investigator&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Months</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Michael Zappitelli, MD</last_name>
    <phone>416-813-7654</phone>
    <phone_ext>304077</phone_ext>
    <email>michael.zappitelli@sickkids.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jasmine Lee, MSc</last_name>
    <phone>416-813-7654</phone>
    <phone_ext>309010</phone_ext>
    <email>jasmine.lee@sickkids.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>London Health Sciences Centre</name>
      <address>
        <city>London</city>
        <state>ONT</state>
        <zip>N6A 5W9</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kathie Baer, MSc</last_name>
      <phone>(519) 685-8500</phone>
      <phone_ext>54524</phone_ext>
      <email>kathie.baer@lhsc.on.ca</email>
    </contact>
    <contact_backup>
      <last_name>Robin Sachdeva, PhD</last_name>
      <email>Robin.Sachdeva@lhsc.on.ca</email>
    </contact_backup>
    <investigator>
      <last_name>Sara Kuruvilla, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>June 18, 2020</study_first_submitted>
  <study_first_submitted_qc>June 18, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 22, 2020</study_first_posted>
  <last_update_submitted>June 30, 2021</last_update_submitted>
  <last_update_submitted_qc>June 30, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 2, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Hospital for Sick Children</investigator_affiliation>
    <investigator_full_name>Michael Zappitelli</investigator_full_name>
    <investigator_title>Clinician Scientist</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acute Kidney Injury</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04442516
org study id: CisP Metabolomics
nct id: NCT04442516
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Cisplatin (CisP) is a chemotherapeutic agent used to treat head and neck and lung cancer in
      adults and over 15 different pediatric cancers. Despite its known toxicity, CisP is still
      widely used as a first line chemotherapy as it is so effective. Nephrotoxicity is one of the
      most common adverse effects of CisP, occurring in 20-50% of patients. It manifests as acute
      kidney injury (AKI) typically within the first few days of exposure and is associated with
      short and long-term morbidity. Furthermore, AKI diagnosis is only possible once kidney damage
      has progressed to functional impairment, when mitigation strategies are ineffective. Tests
      that could predict AKI risk pre-emptively or diagnose early-stage AKI before functional loss
      would be very impactful, affording opportunities for prevention or early intervention to
      mitigate CisP nephrotoxicity, reduce morbidity and improve health outcomes.

      The field of metabolomics seeks to identify patterns of small molecules (metabolites)
      involved in cell or tissue metabolism related to disease states, or patient factors like
      lifestyle and genetics. Plasma and urine are ideal for sampling the metabolome, which can
      identify at-risk patients and reveal disease-related changes earlier than existing diagnostic
      methods do.

      In CisP-treated children and adults from across Canada, we will identify urine and plasma
      metabolite profiles a) prior to CisP dosing that predict CisP AKI risk, and b) shortly after
      dosing to identify early-stage nephrotoxicity, before clinical signs of AKI are detectable.
      Our identified biomarkers will allow individualization of CisP treatment based on the level
      of nephrotoxicity risk and the design of trials to mitigate the progression and complications
      of CisP nephrotoxicity.
observational model: Cohort
time perspective: Prospective
measure: To identify patterns of metabolites and specific metabolites prior to and shortly after CisP treatment that predict AKI risk and identify the onset of AKI early (discovery cohort).
time frame: 8+ years
measure: To independently validate our findings and develop a precision medicine algorithm using metabolites to predict patients at high risk for developing CisP AKI (validation cohort).
time frame: 8+ years
arm group label: Adults receiving Cisplatin as part of their cancer therapy
arm group label: Children receiving Cisplatin as part of their cancer therapy
intervention type: Other
intervention name: Questionnaire, sampling of blood, urine and saliva
description: We are following patients who are receiving Cisplatin as part of their cancer therapy.
arm group label: Adults receiving Cisplatin as part of their cancer therapy
arm group label: Children receiving Cisplatin as part of their cancer therapy
Urinary and plasma metabolites and saliva or blood sample for DNA.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 3 Months
maximum age: N/A
healthy volunteers: No
last name: Michael Zappitelli, MD
phone: 416-813-7654
phone ext: 304077
email: michael.zappitelli@sickkids.ca
last name: Jasmine Lee, MSc
phone: 416-813-7654
phone ext: 309010
email: jasmine.lee@sickkids.ca
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: The Hospital for Sick Children
investigator full name: Michael Zappitelli
investigator title: Clinician Scientist
mesh term: Acute Kidney Injury
sharing ipd: Undecided