<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/NCT01711268</url>
  </required_header>
  <id_info>
    <org_study_id>HGWH008</org_study_id>
    <nct_id>NCT01711268</nct_id>
  </id_info>
  <brief_title>Sunitinib Drug Levels and Outcomes in Kidney Cancer</brief_title>
  <acronym>CRESTO</acronym>
  <official_title>Correlating Renal Cell Cancer Treatment Efficacy With Sunitinib Therapeutic Levels and Outcomes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Western Sydney Local Health District</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Western Sydney Local Health District</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Sunitinib is an oral drug used for treatment of advanced kidney cancer. The standard dose is&#xD;
      50mg, but many patients require a dose decrease due to side-effects. Drug levels of sunitinib&#xD;
      vary approximately 10-fold between patients.&#xD;
&#xD;
      This study will measure blood levels of sunitinib and its metabolite, and correlate these&#xD;
      with side-effects and the response to the treatment. The study aims to establish whether&#xD;
      blood levels change with time, and see how useful blood levels are for monitoring patients&#xD;
      treated with sunitinib.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Rationale: Sunitinib is an oral multi-targeted tyrosine kinase inhibitor used for first-line&#xD;
      systemic therapy in metastatic renal cell carcinoma. It is metabolised to a pharmacologically&#xD;
      active metabolite, SU012662, which is of equal potency to the parent compound. At a standard&#xD;
      50mg daily dose, variability in plasma levels between patients is approximately ten-fold. In&#xD;
      clinical trials, over 30% of patients require a dose reduction due to toxicity. However, some&#xD;
      patients can tolerate up to 100mg without excessive toxicity. It is unknown if sunitinib&#xD;
      clearance changes with time. Pre-clinical experiments observed tyrosine kinase inhibition at&#xD;
      a plasma concentration of 50-100ng/ml.&#xD;
&#xD;
      Design: This is a prospective non-randomized, Phase II clinical study. Decision to treat&#xD;
      patients with single-agent sunitinib is pre-determined by treating specialists before&#xD;
      entering this study. Toxicity and trough sunitinib/metabolite levels will be measured every&#xD;
      six weeks during treatment.&#xD;
&#xD;
      Aim: This study will prospectively examine the relationship between steady-state trough&#xD;
      levels of sunitinib/metabolites and the time on treatment, in addition to changes in trough&#xD;
      levels over time. Trough levels will also be correlated with other measures of efficacy and&#xD;
      treatment-related toxicity. Furthermore, we aim to confirm that the putative target of&#xD;
      50ng/ml correlates with toxicity and time on sunitinib.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>May 2012</start_date>
  <completion_date type="Anticipated">December 2014</completion_date>
  <primary_completion_date type="Anticipated">December 2014</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>Time to treatment failure (time on sunitinib treatment)</measure>
    <time_frame>Sunitinib duration (median)</time_frame>
    <description>This duration extends from the date the patient starts sunitinib until the date sunitinib is abandoned. The group with sunitinib concentration below the population median are expected to have a median Time to Treatment Failure (TTF) of approximately 8 months, compared with 14 months in those with sunitinib concentration above the population median.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Toxicity</measure>
    <time_frame>Every 6 weeks</time_frame>
    <description>Pre-specified toxicities (BP, fatigue, diarrhoea, stomatitis, hand-foot syndrome) will be graded every 6 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>2 years</time_frame>
    <description>Measured from the date of starting sunitinib treatment to the date of death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>2 years</time_frame>
    <description>Progression as determined by the clinician according to RECIST 1.1 definitions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to second line therapy</measure>
    <time_frame>2 years</time_frame>
    <description>Date of starting sunitinib treatment to the date further systemic therapy is started</description>
  </secondary_outcome>
  <enrollment type="Anticipated">35</enrollment>
  <condition>Renal Cell Carcinoma</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Whole blood&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Adults being treated with sunitinib monotherapy for metastatic renal cell carcinoma&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Metastatic renal cell cancer treated with single agent sunitinib&#xD;
&#xD;
          -  No known primary liver disease and no other severe or uncontrolled concurrent medical&#xD;
             conditions&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who are unable to sign informed consent&#xD;
&#xD;
          -  Patients unable to give blood&#xD;
&#xD;
          -  Patients who are pregnant, nursing or not using an effective contraception method&#xD;
&#xD;
          -  Patients who had bone-marrow-transplantation prior to sunitinib treatment&#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>Howard Gurney, MBBS, FRACP</last_name>
    <role>Principal Investigator</role>
    <affiliation>Crown Princess Mary Cancer Centre, Westmead</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Howard Gurney, MBBS, FRACP</last_name>
    <phone>+61298455200</phone>
    <email>howard.gurney@sydney.edu.au</email>
  </overall_contact>
  <location>
    <facility>
      <name>Crown Princess Mary Cancer Centre, Westmead Hospital</name>
      <address>
        <city>Westmead</city>
        <state>New South Wales</state>
        <zip>2145</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Howard Gurney, MBBS (Hon), FRACP</last_name>
      <phone>+61298455200</phone>
      <email>howard.gurney@sydney.edu.au</email>
    </contact>
    <investigator>
      <last_name>Howard Gurney, MBBS (Hon), FRACP</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>May 2014</verification_date>
  <study_first_submitted>August 2, 2012</study_first_submitted>
  <study_first_submitted_qc>October 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 22, 2012</study_first_posted>
  <last_update_submitted>May 13, 2014</last_update_submitted>
  <last_update_submitted_qc>May 13, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 15, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Western Sydney Local Health District</investigator_affiliation>
    <investigator_full_name>Howard Gurney</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Sunitinib</keyword>
  <keyword>Renal Cell Carcinoma</keyword>
  <keyword>Therapeutic Drug Monitoring</keyword>
  <keyword>Pharmacokinetic</keyword>
  <keyword>Treatment toxicity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Renal Cell</mesh_term>
  </condition_browse>
  <!-- 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/NCT01711268
org study id: HGWH008
nct id: NCT01711268
lead sponsor: 
has dmc: No
Sunitinib is an oral drug used for treatment of advanced kidney cancer. The standard dose is
      50mg, but many patients require a dose decrease due to side-effects. Drug levels of sunitinib
      vary approximately 10-fold between patients.

      This study will measure blood levels of sunitinib and its metabolite, and correlate these
      with side-effects and the response to the treatment. The study aims to establish whether
      blood levels change with time, and see how useful blood levels are for monitoring patients
      treated with sunitinib.
Rationale: Sunitinib is an oral multi-targeted tyrosine kinase inhibitor used for first-line
      systemic therapy in metastatic renal cell carcinoma. It is metabolised to a pharmacologically
      active metabolite, SU012662, which is of equal potency to the parent compound. At a standard
      50mg daily dose, variability in plasma levels between patients is approximately ten-fold. In
      clinical trials, over 30% of patients require a dose reduction due to toxicity. However, some
      patients can tolerate up to 100mg without excessive toxicity. It is unknown if sunitinib
      clearance changes with time. Pre-clinical experiments observed tyrosine kinase inhibition at
      a plasma concentration of 50-100ng/ml.

      Design: This is a prospective non-randomized, Phase II clinical study. Decision to treat
      patients with single-agent sunitinib is pre-determined by treating specialists before
      entering this study. Toxicity and trough sunitinib/metabolite levels will be measured every
      six weeks during treatment.

      Aim: This study will prospectively examine the relationship between steady-state trough
      levels of sunitinib/metabolites and the time on treatment, in addition to changes in trough
      levels over time. Trough levels will also be correlated with other measures of efficacy and
      treatment-related toxicity. Furthermore, we aim to confirm that the putative target of
      50ng/ml correlates with toxicity and time on sunitinib.
observational model: Cohort
time perspective: Prospective
measure: Time to treatment failure (time on sunitinib treatment)
time frame: Sunitinib duration (median)
description: This duration extends from the date the patient starts sunitinib until the date sunitinib is abandoned. The group with sunitinib concentration below the population median are expected to have a median Time to Treatment Failure (TTF) of approximately 8 months, compared with 14 months in those with sunitinib concentration above the population median.
measure: Toxicity
time frame: Every 6 weeks
description: Pre-specified toxicities (BP, fatigue, diarrhoea, stomatitis, hand-foot syndrome) will be graded every 6 weeks
measure: Overall survival
time frame: 2 years
description: Measured from the date of starting sunitinib treatment to the date of death from any cause
measure: Progression-free survival
time frame: 2 years
description: Progression as determined by the clinician according to RECIST 1.1 definitions
measure: Time to second line therapy
time frame: 2 years
description: Date of starting sunitinib treatment to the date further systemic therapy is started
Whole blood
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Howard Gurney, MBBS, FRACP
role: Principal Investigator
affiliation: Crown Princess Mary Cancer Centre, Westmead
last name: Howard Gurney, MBBS, FRACP
phone: +61298455200
email: howard.gurney@sydney.edu.au
facility: 
status: Recruiting
contact: 
investigator: 
country: Australia
responsible party type: Principal Investigator
investigator affiliation: Western Sydney Local Health District
investigator full name: Howard Gurney
investigator title: Associate Professor
mesh term: Carcinoma, Renal Cell