<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/NCT03013920</url>
  </required_header>
  <id_info>
    <org_study_id>2016_088</org_study_id>
    <nct_id>NCT03013920</nct_id>
  </id_info>
  <brief_title>CLE Characteristics of Upper Urinary Tract Urothelial Carcinoma</brief_title>
  <official_title>A Prospective In-Vivo Human Pilot Study to Assess Confocal Laser Endomicroscopy Characteristics of Upper Tract Urothelial Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Rationale: Initial evaluation usually consists of cross sectional imaging of the urinary&#xD;
      tract. When a suspect lesion is seen, an ureterorenoscopy is planned to visualize the lesion&#xD;
      and to collect tissue for histopathology. These techniques are considered to be the gold&#xD;
      standard in diagnosis of UTUC. CLE, a high resolution imaging technique that can be used in&#xD;
      combination with endo-urological procedures, seems promising to improve diagnosis of&#xD;
      urothelial cancer. CLE image characteristics for UTUC still have to be defined.&#xD;
&#xD;
      Objective: With this IDEAL stage 2b explorative pilot study the investigators aim to assess&#xD;
      in-vivo CLE image characteristics of normal urothelium, benign urothelium and urothelial&#xD;
      carcinoma (low-grade, high-grade or CIS) of the upper urinary tract by qualitatively&#xD;
      comparing CLE images with both histopathology from diagnostic biopsies and pathology from the&#xD;
      therapeutic radical nephroureterectomy. Secondary objectives are the development of an&#xD;
      imaging atlas and to assess the technical feasibility and procedure related adverse events of&#xD;
      CLE.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a prospective, mono-center observational human, in vivo pilot study to assess&#xD;
      in-vivo CLE characteristics of normal urothelium, benign urothelium and urothelial carcinoma&#xD;
      (low-grade, high-grade or CIS) of the upper urinary tract. Eligible patients have a suspect&#xD;
      tumour in the upper urinary tract and are scheduled for a diagnostic URS. Eligible patients&#xD;
      will be informed about this study by their urologist. Information about the study will be&#xD;
      provided both verbally and in written form.&#xD;
&#xD;
      CLE images are recorded using a probe-based system (Cellvizio 100 series, Mauna Kea&#xD;
      Technologies, Paris, France). The probe has a diameter of 0,85 mm, hereby enabling passage&#xD;
      through the working channel of ureterorenoscope. It has a depth of tissue penetration of 50&#xD;
      µm, a field of view of 320 µm and a resolution of 3,5 µm. Images are collected at a scan rate&#xD;
      of 12 frames per second. Using the Cellvizio Viewer system, we can observe mucosal&#xD;
      microarchitecture with an increased field of view through mosaic post processing. This system&#xD;
      also enables virtual staining of mucosal structures to further enhance tissue contrast.&#xD;
&#xD;
      A fluorescent contrast agent is needed to obtain CLE images. Fluorescein&#xD;
      (fluoresceinedinatrium, Fresenius Kabi, Zeist, Nederland), a non-toxic and commonly used&#xD;
      fluorescent dye will be administered through the working channel of the ureterorenoscope into&#xD;
      the pyelocaliceal system (3 - 5 mL 0.1% fluorescein diluted in saline) and left indwelling&#xD;
      for 5 minutes to stain the extracellular matrix.&#xD;
&#xD;
      In this study patients will undergo one CLE measurement during the planned diagnostic URS. We&#xD;
      measure on average 2 regions of interest per patient. If a patient has multiple tumours we&#xD;
      will do multiple measurements. The measurement duration per patient adds maximally 10 minutes&#xD;
      during the URS. At a later stage two independent non-blinded observers will review the CLE&#xD;
      images. The CLE images of the diagnostic URS are qualitatively compared with histopathology&#xD;
      from diagnostic biopsies, and if performed also with pathology from the therapeutic&#xD;
      nephroureterectomy.&#xD;
&#xD;
      Based on the UTUC diagnosis from the diagnostic URS, in general about one third of the&#xD;
      patients are indicated for a therapeutic radical nephroureterectomy. The other two thirds of&#xD;
      the UTUC patients are treated with endoscopic treatment. If patients undergo several&#xD;
      ureterorenoscopies, they may be approached for CLE measurements at consecutive&#xD;
      ureterorenoscopies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2016</start_date>
  <completion_date type="Actual">April 2018</completion_date>
  <primary_completion_date type="Actual">April 2018</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>In-vivo CLE measurements of normal urothelium and urothelial carcinoma (low-grade, high-grade or CIS) of the upper urinary tract</measure>
    <time_frame>3 years</time_frame>
    <description>The CLE measurements are qualitatively correlated to the corresponding histopathology</description>
  </primary_outcome>
  <enrollment type="Actual">150</enrollment>
  <condition>Urinary Tract Cancer</condition>
  <condition>Urothelial Carcinoma</condition>
  <condition>Ureter Cancer</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      CLE images and histopathology&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Adult patients with a suspect tumour in the upper urinary tract, who are planned for a&#xD;
        diagnostic URS, are eligible for this study.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients &gt;18 years&#xD;
&#xD;
          -  Suspect upper urinary tract urothelial carcinoma&#xD;
&#xD;
          -  Scheduled for diagnostic URS&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients &lt;18 years&#xD;
&#xD;
          -  Patients with known allergy for fluorescein&#xD;
&#xD;
          -  Possible pregnancy or lactating women&#xD;
&#xD;
          -  Patients not eligible for radical treatment of UTUC&#xD;
&#xD;
          -  No signed informed consent&#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>Jean J de la Rosette, prof. dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Academic Medical Center</name>
      <address>
        <city>Amsterdam</city>
        <zip>1105AZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>June 2018</verification_date>
  <study_first_submitted>December 28, 2016</study_first_submitted>
  <study_first_submitted_qc>January 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 9, 2017</study_first_posted>
  <last_update_submitted>June 5, 2018</last_update_submitted>
  <last_update_submitted_qc>June 5, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">June 6, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</investigator_affiliation>
    <investigator_full_name>Prof.dr. J.J.M.C.H. de la Rosette</investigator_full_name>
    <investigator_title>Prof. dr. JJMCH de la Rosette</investigator_title>
  </responsible_party>
  <keyword>upper urinary tract cancer</keyword>
  <keyword>confocal laser endomicroscopy</keyword>
  <keyword>urothelial carcinoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Transitional Cell</mesh_term>
    <mesh_term>Ureteral Neoplasms</mesh_term>
    <mesh_term>Urologic Neoplasms</mesh_term>
  </condition_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/NCT03013920
org study id: 2016_088
nct id: NCT03013920
lead sponsor: 
has dmc: No
Rationale: Initial evaluation usually consists of cross sectional imaging of the urinary
      tract. When a suspect lesion is seen, an ureterorenoscopy is planned to visualize the lesion
      and to collect tissue for histopathology. These techniques are considered to be the gold
      standard in diagnosis of UTUC. CLE, a high resolution imaging technique that can be used in
      combination with endo-urological procedures, seems promising to improve diagnosis of
      urothelial cancer. CLE image characteristics for UTUC still have to be defined.

      Objective: With this IDEAL stage 2b explorative pilot study the investigators aim to assess
      in-vivo CLE image characteristics of normal urothelium, benign urothelium and urothelial
      carcinoma (low-grade, high-grade or CIS) of the upper urinary tract by qualitatively
      comparing CLE images with both histopathology from diagnostic biopsies and pathology from the
      therapeutic radical nephroureterectomy. Secondary objectives are the development of an
      imaging atlas and to assess the technical feasibility and procedure related adverse events of
      CLE.
This study is a prospective, mono-center observational human, in vivo pilot study to assess
      in-vivo CLE characteristics of normal urothelium, benign urothelium and urothelial carcinoma
      (low-grade, high-grade or CIS) of the upper urinary tract. Eligible patients have a suspect
      tumour in the upper urinary tract and are scheduled for a diagnostic URS. Eligible patients
      will be informed about this study by their urologist. Information about the study will be
      provided both verbally and in written form.

      CLE images are recorded using a probe-based system (Cellvizio 100 series, Mauna Kea
      Technologies, Paris, France). The probe has a diameter of 0,85 mm, hereby enabling passage
      through the working channel of ureterorenoscope. It has a depth of tissue penetration of 50
      µm, a field of view of 320 µm and a resolution of 3,5 µm. Images are collected at a scan rate
      of 12 frames per second. Using the Cellvizio Viewer system, we can observe mucosal
      microarchitecture with an increased field of view through mosaic post processing. This system
      also enables virtual staining of mucosal structures to further enhance tissue contrast.

      A fluorescent contrast agent is needed to obtain CLE images. Fluorescein
      (fluoresceinedinatrium, Fresenius Kabi, Zeist, Nederland), a non-toxic and commonly used
      fluorescent dye will be administered through the working channel of the ureterorenoscope into
      the pyelocaliceal system (3 - 5 mL 0.1% fluorescein diluted in saline) and left indwelling
      for 5 minutes to stain the extracellular matrix.

      In this study patients will undergo one CLE measurement during the planned diagnostic URS. We
      measure on average 2 regions of interest per patient. If a patient has multiple tumours we
      will do multiple measurements. The measurement duration per patient adds maximally 10 minutes
      during the URS. At a later stage two independent non-blinded observers will review the CLE
      images. The CLE images of the diagnostic URS are qualitatively compared with histopathology
      from diagnostic biopsies, and if performed also with pathology from the therapeutic
      nephroureterectomy.

      Based on the UTUC diagnosis from the diagnostic URS, in general about one third of the
      patients are indicated for a therapeutic radical nephroureterectomy. The other two thirds of
      the UTUC patients are treated with endoscopic treatment. If patients undergo several
      ureterorenoscopies, they may be approached for CLE measurements at consecutive
      ureterorenoscopies.
observational model: Cohort
time perspective: Prospective
measure: In-vivo CLE measurements of normal urothelium and urothelial carcinoma (low-grade, high-grade or CIS) of the upper urinary tract
time frame: 3 years
description: The CLE measurements are qualitatively correlated to the corresponding histopathology
CLE images and histopathology
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jean J de la Rosette, prof. dr.
role: Principal Investigator
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
facility: 
country: Netherlands
responsible party type: Principal Investigator
investigator affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
investigator full name: Prof.dr. J.J.M.C.H. de la Rosette
investigator title: Prof. dr. JJMCH de la Rosette
mesh term: Carcinoma
mesh term: Carcinoma, Transitional Cell
mesh term: Ureteral Neoplasms
mesh term: Urologic Neoplasms
sharing ipd: No