<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/NCT02968732</url>
  </required_header>
  <id_info>
    <org_study_id>GU-095</org_study_id>
    <nct_id>NCT02968732</nct_id>
  </id_info>
  <brief_title>Cystoscopic Evaluation Predicting pT0 Urothelial Carcinoma of the Bladder</brief_title>
  <official_title>Assessment of Reliability of Cystoscopic Evaluation Predicting pT0 Urothelial Carcinoma of the Bladder at the Time of Radical Cystectomy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fox Chase Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Temple University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Fox Chase Cancer Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A prospective, investigational study to assess the accuracy of standardized cystoscopic&#xD;
      evaluation with tissue sampling performed immediately prior to definitive radical cystectomy&#xD;
      to predict pathologic tumor stage and identify patients who may benefit from bladder&#xD;
      preservation therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Archival specimen of prior diagnostic TUR will be prepared as 10-20 unstained 5-10 micron&#xD;
      slides to under-go next generation sequencing and be compared to final cystectomy specimen to&#xD;
      investigate potential pre-treatment signatures predictive of response to chemotherapy and to&#xD;
      understand genomic evolution of primary tumors after chemotherapy. All patients will also&#xD;
      have urine, PBMC, and serum/plasma collected at baseline, day of procedure, 4-6 weeks&#xD;
      post-procedure, and 6 months post-procedure. The baseline samples will be collected prior to&#xD;
      any chemotherapy administration and prior to the procedure.&#xD;
&#xD;
      On the day of the patient's radical cystectomy, standard rigid cystourethroscopy will be&#xD;
      performed. A urine sample will be collected from the bladder. A plasma sample will be&#xD;
      collected while the patient is under anesthesia or in pre-op holding area. Visible tumor and&#xD;
      prior tumor sites will be targeted for tissue sampling (no more than two sites will be&#xD;
      targeted). A standardized tumor quantification system will be employed to document location&#xD;
      and presence of tumor and previous biopsy sites. To this end, the investigators have&#xD;
      developed a novel scoring system that allows for objective quantification of endoscopic&#xD;
      findings at the time of cystoscopy and indexes presence and location of papillary tumor,&#xD;
      erythema, and scar. Two additional random biopsies will be obtained, one from the posterior&#xD;
      wall and one from the lateral wall for assessment of genomic signatures within&#xD;
      normal-appearing mucosa.&#xD;
&#xD;
      Tumor location and its relationship to the ureteral orifices will be noted in order to assist&#xD;
      the surgeon in performance of radical cystectomy. The patient will then undergo radical&#xD;
      cystectomy as per standard of care.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">November 11, 2016</start_date>
  <completion_date type="Anticipated">April 1, 2027</completion_date>
  <primary_completion_date type="Actual">August 19, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To evaluate the accuracy of endoscopic assessment in predicting pT0 urothelial disease in the urinary bladder at the time of radical cystectomy.</measure>
    <time_frame>30 days post surgery</time_frame>
    <description>Endoscopic assessments will be performed using a novel scoring system that allows objective quantification of endoscopic findings at the time of cystoscopy. The findings will be compared to final pathological specimen to determine reliability of predicting pTO disease from endoscopic assessment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To determine if genomic tumor signatures from pre-treatment tumor tissue can predict chemotherapy response.</measure>
    <time_frame>up to 5years post surgery</time_frame>
    <description>Archival specimen of prior diagnostic TUR will be prepared as 10-20 unstained 5-10 micron slides to under-go next generation sequencing and be compared to final cystectomy specimen to investigate potential pre-treatment signatures predictive of response to chemotherapy. Chemotherapy response will be measured by pathological assessment of residual tumor at cystectomy and graded by TNM staging criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To determine how genomic tumor signatures compare before and after chemotherapy administration.</measure>
    <time_frame>up to 5years post surgery</time_frame>
    <description>Archival specimen of prior diagnostic TUR will be prepared as 10-20 unstained 5-10 micron slides to under-go next generation sequencing and be compared to final cystectomy specimen to determine genomic signatures before and after chemotherapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To determine if genomic signature from tissue obtained on endoscopic evaluation just prior to cystectomy can help predict final pathological stage.</measure>
    <time_frame>up to 5years post surgery</time_frame>
    <description>Comparison of baseline archival tumor tissue and final specimen will be compared for whether viable tumor tissue remains at time of surgery, for changes in total number of mutations found, whether specific mutations evolve from before to after chemo, and whether a pre-treatment genomic signature is predictive of chemo response. Specifically, DNA will be isolated from pre- and post- chemotherapy urine samples and subjected to targeted deep sequencing to support the hypothesis that mutation clearance correlates with pathologic response in the radical cystectomy specimen. These studies will provide orthogonal validation and could prove more sensitive than pathological analysis. In addition, they may serve as further basis for highly stringent selection of complete responders in whom cystectomy could be avoided in the future.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">65</enrollment>
  <condition>Urothelial Carcinoma</condition>
  <arm_group>
    <arm_group_label>Surgical</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Radical Cystectomy</intervention_name>
    <arm_group_label>Surgical</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female patients age &gt;18 years at the time of consent.&#xD;
&#xD;
          2. Patients with a diagnosis of urothelial carcinoma clinical stage T1-T4NanyM0.&#xD;
&#xD;
          3. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of&#xD;
             0-3.&#xD;
&#xD;
          4. Patients must have a clinical decision to proceed with radical cystectomy by any&#xD;
             conventional approach (open, laparoscopic, robot-assisted laparoscopic). Time from&#xD;
             decision to surgery is usually 3-8 weeks for those who do not receive neoadjuvant&#xD;
             chemotherapy and 10-14 weeks for those who receive neo-adjuvant chemotherapy&#xD;
             treatment. During this time, eligibility for study participation will be verified.&#xD;
&#xD;
          5. Ability to understand and willingness to sign a written informed consent and HIPAA&#xD;
             authorization document or a legally authorized representative who has the ability to&#xD;
             understand and willingness to sign a written informed consent and HIPAA authorization&#xD;
             on behalf of the participant.&#xD;
&#xD;
          6. Women of reproductive potential must have agreed to use an effective contraceptive&#xD;
             measure.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients who undergo cystectomy with non-curative intent will be excluded.&#xD;
&#xD;
          2. Patients who have undergone any prior pelvic irradiation.&#xD;
&#xD;
          3. Patients who are pregnant or nursing. Radical cystectomy and prolonged general&#xD;
             anesthesia would place the fetus at considerable risk of demise. The prolonged&#xD;
             recovery and debility of the patient would severely limit the patient's ability to&#xD;
             nurse and care for an infant.&#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>Alexander Kutikov, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fox Chase Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fox Chase Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>November 10, 2016</study_first_submitted>
  <study_first_submitted_qc>November 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2016</study_first_posted>
  <last_update_submitted>June 12, 2023</last_update_submitted>
  <last_update_submitted_qc>June 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 13, 2023</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>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Transitional Cell</mesh_term>
    <mesh_term>Urinary Bladder Neoplasms</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/NCT02968732
org study id: GU-095
nct id: NCT02968732
lead sponsor: 
collaborator: 
has dmc: Yes
A prospective, investigational study to assess the accuracy of standardized cystoscopic
      evaluation with tissue sampling performed immediately prior to definitive radical cystectomy
      to predict pathologic tumor stage and identify patients who may benefit from bladder
      preservation therapy.
Archival specimen of prior diagnostic TUR will be prepared as 10-20 unstained 5-10 micron
      slides to under-go next generation sequencing and be compared to final cystectomy specimen to
      investigate potential pre-treatment signatures predictive of response to chemotherapy and to
      understand genomic evolution of primary tumors after chemotherapy. All patients will also
      have urine, PBMC, and serum/plasma collected at baseline, day of procedure, 4-6 weeks
      post-procedure, and 6 months post-procedure. The baseline samples will be collected prior to
      any chemotherapy administration and prior to the procedure.

      On the day of the patient's radical cystectomy, standard rigid cystourethroscopy will be
      performed. A urine sample will be collected from the bladder. A plasma sample will be
      collected while the patient is under anesthesia or in pre-op holding area. Visible tumor and
      prior tumor sites will be targeted for tissue sampling (no more than two sites will be
      targeted). A standardized tumor quantification system will be employed to document location
      and presence of tumor and previous biopsy sites. To this end, the investigators have
      developed a novel scoring system that allows for objective quantification of endoscopic
      findings at the time of cystoscopy and indexes presence and location of papillary tumor,
      erythema, and scar. Two additional random biopsies will be obtained, one from the posterior
      wall and one from the lateral wall for assessment of genomic signatures within
      normal-appearing mucosa.

      Tumor location and its relationship to the ureteral orifices will be noted in order to assist
      the surgeon in performance of radical cystectomy. The patient will then undergo radical
      cystectomy as per standard of care.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: To evaluate the accuracy of endoscopic assessment in predicting pT0 urothelial disease in the urinary bladder at the time of radical cystectomy.
time frame: 30 days post surgery
description: Endoscopic assessments will be performed using a novel scoring system that allows objective quantification of endoscopic findings at the time of cystoscopy. The findings will be compared to final pathological specimen to determine reliability of predicting pTO disease from endoscopic assessment
measure: To determine if genomic tumor signatures from pre-treatment tumor tissue can predict chemotherapy response.
time frame: up to 5years post surgery
description: Archival specimen of prior diagnostic TUR will be prepared as 10-20 unstained 5-10 micron slides to under-go next generation sequencing and be compared to final cystectomy specimen to investigate potential pre-treatment signatures predictive of response to chemotherapy. Chemotherapy response will be measured by pathological assessment of residual tumor at cystectomy and graded by TNM staging criteria.
measure: To determine how genomic tumor signatures compare before and after chemotherapy administration.
time frame: up to 5years post surgery
description: Archival specimen of prior diagnostic TUR will be prepared as 10-20 unstained 5-10 micron slides to under-go next generation sequencing and be compared to final cystectomy specimen to determine genomic signatures before and after chemotherapy.
measure: To determine if genomic signature from tissue obtained on endoscopic evaluation just prior to cystectomy can help predict final pathological stage.
time frame: up to 5years post surgery
description: Comparison of baseline archival tumor tissue and final specimen will be compared for whether viable tumor tissue remains at time of surgery, for changes in total number of mutations found, whether specific mutations evolve from before to after chemo, and whether a pre-treatment genomic signature is predictive of chemo response. Specifically, DNA will be isolated from pre- and post- chemotherapy urine samples and subjected to targeted deep sequencing to support the hypothesis that mutation clearance correlates with pathologic response in the radical cystectomy specimen. These studies will provide orthogonal validation and could prove more sensitive than pathological analysis. In addition, they may serve as further basis for highly stringent selection of complete responders in whom cystectomy could be avoided in the future.
arm group label: Surgical
arm group type: Experimental
intervention type: Procedure
intervention name: Radical Cystectomy
arm group label: Surgical
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Alexander Kutikov, MD
role: Principal Investigator
affiliation: Fox Chase Cancer Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Transitional Cell
mesh term: Urinary Bladder Neoplasms