<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/NCT04432909</url>
  </required_header>
  <id_info>
    <org_study_id>CH-urothelial-cancer-marker</org_study_id>
    <nct_id>NCT04432909</nct_id>
  </id_info>
  <brief_title>A Prospective, Multi-centre, Single-blinded Study of UroCAD for Urothelial Carcinoma Diagnosis and Follow-up</brief_title>
  <official_title>A Prospective, Multi-centre, Single-blinded Study of UroCAD for Urothelial Carcinoma Diagnosis and Follow-up</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Changhai Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>RenJi Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The First Affiliated Hospital of Soochow University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Zhejiang Provincial People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Tongji Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Tianjin Medical University Second Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Qilu Hospital of Shandong University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Xibei Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>West China Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Changhai Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Urothelial carcinoma (UC) is common malignancy and is considered to be one of the costliest&#xD;
      cancers. The traditional diagnostic methods of UC present with some shortcomings. For&#xD;
      example, the specificity of CTU remains low while cystoscopy is invasive and expensive.&#xD;
      Therefore, a noninvasive diagnostic method with high accuracy is urgently needed. Our&#xD;
      previous study has proved that UroCAD, which is able to detect chromosomal aberrations of the&#xD;
      urine exfoliated cells, is a reliable method in diagnosing UC with sensitivity and&#xD;
      specificity of 82.5% and 96.9%, respectively. But its potential in UC patient follow-up&#xD;
      hasn't been assessed yet and the the accuracy of UroCAD in detecting UC still need to be&#xD;
      further validated. The investigators here intended to investigate whether UroCAD can be used&#xD;
      in UC patient follow-up and further validate the accuracy of UroCAD in diagnosing UC.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The traditional diagnostic methods of UC include CT urography (CTU) and cystoscopy. To access&#xD;
      the upper urinary tract, CTU is commonly used. The sensitivity for detecting upper tract&#xD;
      urothelial cancer with CTU has been reported to reach 89%. However, the specificity of CTU is&#xD;
      51% and it cannot get a biopsy sample. Other shortcomings include exposing the patient to&#xD;
      high dose of radiation and the contrast material usage may impair the renal function. In the&#xD;
      context of diagnosing lower urinary tract cancer, cystoscopy is the &quot;gold standard&quot;&#xD;
      diagnostic procedure, which has a sensitivity of 68-83%. But it is invasive, uncomfortable&#xD;
      and may miss flat lesions. Furthermore, due to the high recurrence rate of bladder cancer,&#xD;
      surveillance of the disease with frequent cystoscopy make it one of the costliest cancers.&#xD;
      Therefore, a noninvasive diagnostic method with high accuracy is urgently needed.&#xD;
&#xD;
      Copy number variations (CNVs) refers to the ongoing acquisition of genomic alterations&#xD;
      ranging from point mutations to gross chromosomal rearrangements, is a hallmark of cancer&#xD;
      which is found in 60-80% of human cancer, and it positively correlates with high tumor stage,&#xD;
      poor prognosis, metastasis and therapeutic resistance. Several researches have investigated&#xD;
      the value of detecting chromosomal instability with sWGS in either cell-free (cf)DNA or&#xD;
      genomic DNA as a noninvasive diagnostic method for cancers and yielded quite fine results.&#xD;
      Our previous research has also proved the UroCAD model reached performance of AUC=0.928, with&#xD;
      sensitivity, specificity and accuracy of 82.5%, 96.9% and 89.0%, respectively. This test also&#xD;
      showed superiority in diagnosing upper tract urothelial cancer compared with urinary cytology&#xD;
      test.&#xD;
&#xD;
      Here the investigators intended to conduct a prospective, multicenter, single-blinded&#xD;
      research to further validate the value of UroCAD in diagnosing UC and investigate the&#xD;
      potential of UroCAD in UC patient follow-up by analyzing the CNV level of patient DNA&#xD;
      extracted from urine exfoliated cells and follow UC patient for up to 2 years to determine if&#xD;
      there is a correlation between CNV level and patient prognosis. Patient information, which is&#xD;
      acquired every 3 months after surgery, including survival status, CNV level in urine&#xD;
      exfoliated cells, treatment during this period, medical examination during this period, etc.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 17, 2020</start_date>
  <completion_date type="Anticipated">June 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">January 30, 2022</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>Sensitivity and Specificity of urinalysis by UroCAD analysis</measure>
    <time_frame>through study completion, an average of 30 months</time_frame>
    <description>number of patients &quot;declared positive&quot; with the UroCAD test among the patients suffered from urothelial carcinoma and number of patients &quot;declared negative&quot; with the UCAD test among the patients without cancer.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assess the value of UroCAD for urothelial cancer patient follow-up</measure>
    <time_frame>through study completion, an average of 30 months</time_frame>
    <description>Compare the CNV level with the patient information gathered by follow-up to determine whether there is a correlation between CNV level and patient prognosis or disease progression</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Identification of the correlation between the level of CNV and the grade of the tumor sample</measure>
    <time_frame>through study completion, an average of 30 months</time_frame>
    <description>level of CNV in the urine sample compared with the grade of the tumor confirmed by histopathologic examination</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Identification of the correlation between the level of CNV and the stage of the tumor sample</measure>
    <time_frame>through study completion, an average of 30 months</time_frame>
    <description>level of CNV in the urine sample compared with the stage of the tumor confirmed by histopathologic examination</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of the sensitivity and specificity of the UroCAD analysis versus urine cytology</measure>
    <time_frame>through study completion, an average of 30 months</time_frame>
    <description>number of patients &quot;declared positive&quot; with the UroCAD analysis versus patients &quot;declared positive&quot; with the urine cytology and number of patients &quot;declared negative&quot; with the UroCAD analysis versus patients &quot; declared negative &quot; with the urine cytology</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">500</enrollment>
  <condition>Urothelial Carcinoma</condition>
  <arm_group>
    <arm_group_label>Urothelial carcinoma group</arm_group_label>
    <description>Pre-surgery patients with urothelial carcinoma will be the experimental group to determine the sensitivity and specificity of UroCAD analysis, the result will be compared with cytology and FISH test.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-cancer participants</arm_group_label>
    <description>Patients being treated for other diseases but without any tumor will provide a negative control to provide data for determining the sensitivity and specificity of UroCAD analysis.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>The level of CNV</intervention_name>
    <description>The extracted DNA from morning urine will be analyzed by UroCAD to determine the level of CNV. And the patient will be followed for up to 2 years.</description>
    <arm_group_label>Non-cancer participants</arm_group_label>
    <arm_group_label>Urothelial carcinoma group</arm_group_label>
    <other_name>UroCAD test of the urine exfoliated cells</other_name>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      DNA from Urine Exfoliated Cells will be analyzed&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients diagnosed with urothelial carcinoma or participants in control group from January&#xD;
        2020 to June 2022 in 10 hospitals including Changhai hospital, Renji hospital, The First&#xD;
        Affiliated Hospital of Suchow university, Zhejiang Provincial people's hospital, Tongji&#xD;
        hospital, The second hospital of Tianjin medical university, Qilu hospital, Second&#xD;
        Affiliated Hospital of Sun Yat-Sen University, Xibei hospital, West China hospital.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients diagnosed with urothelial carcinoma and planned to undergo surgery&#xD;
&#xD;
          -  Cancer patient with urine cytology test result&#xD;
&#xD;
          -  Cancer patient willing to provide urine sample before the surgery, 3 months after&#xD;
             surgery, 6 months after surgery, 12 month after surgery, 15 months after surgery, 18&#xD;
             months after surgery, 21 months after surgery, 24 months after surgery, and willing to&#xD;
             provide patient information.&#xD;
&#xD;
          -  Participants without any tumor disease and willing to attend the study by providing&#xD;
             morning urine.&#xD;
&#xD;
          -  Male or female patients aged &gt;= 18 years.&#xD;
&#xD;
          -  Participants signed informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age under 18 years&#xD;
&#xD;
          -  Individuals unwilling to sign the consent form or unwilling to provide morning urine&#xD;
             for test or unwilling to provide the medical record.&#xD;
&#xD;
          -  Patient already received suprapubic cystostomy or urethral catheterization.&#xD;
&#xD;
          -  Patient with late-stage uremia and need regular dialysis.&#xD;
&#xD;
          -  Patient with cancer other than urothelial carcinoma.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Chuanliang Xu, M.D.,Ph.D.</last_name>
    <role>Study Chair</role>
    <affiliation>Changhai Hospital, Shanghai</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Shuxiong Zeng, M.D., Ph.D.</last_name>
    <phone>+8618930568759</phone>
    <email>zengshuxiong@126.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Changhai Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200433</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Shuxiong Zeng, M.D. Ph.D</last_name>
      <phone>+8618930568759</phone>
      <email>zengshuxiong@126.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Wadhwa N, Mathew BB, Jatawa SK, Tiwari A. Genetic instability in urinary bladder cancer: An evolving hallmark. J Postgrad Med. 2013 Oct-Dec;59(4):284-8. doi: 10.4103/0022-3859.123156.</citation>
    <PMID>24346386</PMID>
  </reference>
  <reference>
    <citation>Bakhoum SF, Ngo B, Laughney AM, Cavallo JA, Murphy CJ, Ly P, Shah P, Sriram RK, Watkins TBK, Taunk NK, Duran M, Pauli C, Shaw C, Chadalavada K, Rajasekhar VK, Genovese G, Venkatesan S, Birkbak NJ, McGranahan N, Lundquist M, LaPlant Q, Healey JH, Elemento O, Chung CH, Lee NY, Imielenski M, Nanjangud G, Pe'er D, Cleveland DW, Powell SN, Lammerding J, Swanton C, Cantley LC. Chromosomal instability drives metastasis through a cytosolic DNA response. Nature. 2018 Jan 25;553(7689):467-472. doi: 10.1038/nature25432. Epub 2018 Jan 17.</citation>
    <PMID>29342134</PMID>
  </reference>
  <reference>
    <citation>Liu H, He W, Wang B, Xu K, Han J, Zheng J, Ren J, Shao L, Bo S, Lu S, Lin T, Huang J. MALBAC-based chromosomal imbalance analysis: a novel technique enabling effective non-invasive diagnosis and monitoring of bladder cancer. BMC Cancer. 2018 Jun 15;18(1):659. doi: 10.1186/s12885-018-4571-7.</citation>
    <PMID>29907142</PMID>
  </reference>
  <reference>
    <citation>Hieronymus H, Murali R, Tin A, Yadav K, Abida W, Moller H, Berney D, Scher H, Carver B, Scardino P, Schultz N, Taylor B, Vickers A, Cuzick J, Sawyers CL. Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death. Elife. 2018 Sep 4;7:e37294. doi: 10.7554/eLife.37294.</citation>
    <PMID>30178746</PMID>
  </reference>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>June 12, 2020</study_first_submitted>
  <study_first_submitted_qc>June 12, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>September 8, 2021</last_update_submitted>
  <last_update_submitted_qc>September 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 16, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Changhai Hospital</investigator_affiliation>
    <investigator_full_name>Shuxiong Zeng</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>diagnosis</keyword>
  <keyword>follow-up</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>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>We will try to protect the information of the included participants</ipd_description>
  </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/NCT04432909
org study id: CH-urothelial-cancer-marker
nct id: NCT04432909
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
Urothelial carcinoma (UC) is common malignancy and is considered to be one of the costliest
      cancers. The traditional diagnostic methods of UC present with some shortcomings. For
      example, the specificity of CTU remains low while cystoscopy is invasive and expensive.
      Therefore, a noninvasive diagnostic method with high accuracy is urgently needed. Our
      previous study has proved that UroCAD, which is able to detect chromosomal aberrations of the
      urine exfoliated cells, is a reliable method in diagnosing UC with sensitivity and
      specificity of 82.5% and 96.9%, respectively. But its potential in UC patient follow-up
      hasn't been assessed yet and the the accuracy of UroCAD in detecting UC still need to be
      further validated. The investigators here intended to investigate whether UroCAD can be used
      in UC patient follow-up and further validate the accuracy of UroCAD in diagnosing UC.
The traditional diagnostic methods of UC include CT urography (CTU) and cystoscopy. To access
      the upper urinary tract, CTU is commonly used. The sensitivity for detecting upper tract
      urothelial cancer with CTU has been reported to reach 89%. However, the specificity of CTU is
      51% and it cannot get a biopsy sample. Other shortcomings include exposing the patient to
      high dose of radiation and the contrast material usage may impair the renal function. In the
      context of diagnosing lower urinary tract cancer, cystoscopy is the "gold standard"
      diagnostic procedure, which has a sensitivity of 68-83%. But it is invasive, uncomfortable
      and may miss flat lesions. Furthermore, due to the high recurrence rate of bladder cancer,
      surveillance of the disease with frequent cystoscopy make it one of the costliest cancers.
      Therefore, a noninvasive diagnostic method with high accuracy is urgently needed.

      Copy number variations (CNVs) refers to the ongoing acquisition of genomic alterations
      ranging from point mutations to gross chromosomal rearrangements, is a hallmark of cancer
      which is found in 60-80% of human cancer, and it positively correlates with high tumor stage,
      poor prognosis, metastasis and therapeutic resistance. Several researches have investigated
      the value of detecting chromosomal instability with sWGS in either cell-free (cf)DNA or
      genomic DNA as a noninvasive diagnostic method for cancers and yielded quite fine results.
      Our previous research has also proved the UroCAD model reached performance of AUC=0.928, with
      sensitivity, specificity and accuracy of 82.5%, 96.9% and 89.0%, respectively. This test also
      showed superiority in diagnosing upper tract urothelial cancer compared with urinary cytology
      test.

      Here the investigators intended to conduct a prospective, multicenter, single-blinded
      research to further validate the value of UroCAD in diagnosing UC and investigate the
      potential of UroCAD in UC patient follow-up by analyzing the CNV level of patient DNA
      extracted from urine exfoliated cells and follow UC patient for up to 2 years to determine if
      there is a correlation between CNV level and patient prognosis. Patient information, which is
      acquired every 3 months after surgery, including survival status, CNV level in urine
      exfoliated cells, treatment during this period, medical examination during this period, etc.
observational model: Cohort
time perspective: Prospective
measure: Sensitivity and Specificity of urinalysis by UroCAD analysis
time frame: through study completion, an average of 30 months
description: number of patients "declared positive" with the UroCAD test among the patients suffered from urothelial carcinoma and number of patients "declared negative" with the UCAD test among the patients without cancer.
measure: Assess the value of UroCAD for urothelial cancer patient follow-up
time frame: through study completion, an average of 30 months
description: Compare the CNV level with the patient information gathered by follow-up to determine whether there is a correlation between CNV level and patient prognosis or disease progression
measure: Identification of the correlation between the level of CNV and the grade of the tumor sample
time frame: through study completion, an average of 30 months
description: level of CNV in the urine sample compared with the grade of the tumor confirmed by histopathologic examination
measure: Identification of the correlation between the level of CNV and the stage of the tumor sample
time frame: through study completion, an average of 30 months
description: level of CNV in the urine sample compared with the stage of the tumor confirmed by histopathologic examination
measure: Comparison of the sensitivity and specificity of the UroCAD analysis versus urine cytology
time frame: through study completion, an average of 30 months
description: number of patients "declared positive" with the UroCAD analysis versus patients "declared positive" with the urine cytology and number of patients "declared negative" with the UroCAD analysis versus patients " declared negative " with the urine cytology
arm group label: Urothelial carcinoma group
description: Pre-surgery patients with urothelial carcinoma will be the experimental group to determine the sensitivity and specificity of UroCAD analysis, the result will be compared with cytology and FISH test.
arm group label: Non-cancer participants
description: Patients being treated for other diseases but without any tumor will provide a negative control to provide data for determining the sensitivity and specificity of UroCAD analysis.
intervention type: Diagnostic Test
intervention name: The level of CNV
description: The extracted DNA from morning urine will be analyzed by UroCAD to determine the level of CNV. And the patient will be followed for up to 2 years.
arm group label: Non-cancer participants
arm group label: Urothelial carcinoma group
other name: UroCAD test of the urine exfoliated cells
DNA from Urine Exfoliated Cells will be analyzed
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
last name: Chuanliang Xu, M.D.,Ph.D.
role: Study Chair
affiliation: Changhai Hospital, Shanghai
last name: Shuxiong Zeng, M.D., Ph.D.
phone: +8618930568759
email: zengshuxiong@126.com
facility: 
status: Recruiting
contact: 
country: China
citation: Wadhwa N, Mathew BB, Jatawa SK, Tiwari A. Genetic instability in urinary bladder cancer: An evolving hallmark. J Postgrad Med. 2013 Oct-Dec;59(4):284-8. doi: 10.4103/0022-3859.123156.
PMID: 24346386
citation: Bakhoum SF, Ngo B, Laughney AM, Cavallo JA, Murphy CJ, Ly P, Shah P, Sriram RK, Watkins TBK, Taunk NK, Duran M, Pauli C, Shaw C, Chadalavada K, Rajasekhar VK, Genovese G, Venkatesan S, Birkbak NJ, McGranahan N, Lundquist M, LaPlant Q, Healey JH, Elemento O, Chung CH, Lee NY, Imielenski M, Nanjangud G, Pe'er D, Cleveland DW, Powell SN, Lammerding J, Swanton C, Cantley LC. Chromosomal instability drives metastasis through a cytosolic DNA response. Nature. 2018 Jan 25;553(7689):467-472. doi: 10.1038/nature25432. Epub 2018 Jan 17.
PMID: 29342134
citation: Liu H, He W, Wang B, Xu K, Han J, Zheng J, Ren J, Shao L, Bo S, Lu S, Lin T, Huang J. MALBAC-based chromosomal imbalance analysis: a novel technique enabling effective non-invasive diagnosis and monitoring of bladder cancer. BMC Cancer. 2018 Jun 15;18(1):659. doi: 10.1186/s12885-018-4571-7.
PMID: 29907142
citation: Hieronymus H, Murali R, Tin A, Yadav K, Abida W, Moller H, Berney D, Scher H, Carver B, Scardino P, Schultz N, Taylor B, Vickers A, Cuzick J, Sawyers CL. Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death. Elife. 2018 Sep 4;7:e37294. doi: 10.7554/eLife.37294.
PMID: 30178746
responsible party type: Principal Investigator
investigator affiliation: Changhai Hospital
investigator full name: Shuxiong Zeng
investigator title: Principal Investigator
mesh term: Carcinoma
mesh term: Carcinoma, Transitional Cell
sharing ipd: No
ipd description: We will try to protect the information of the included participants