<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/NCT03789253</url>
  </required_header>
  <id_info>
    <org_study_id>201712093RINB</org_study_id>
    <nct_id>NCT03789253</nct_id>
  </id_info>
  <brief_title>Identify Genes/Pathways Responsible for Progression From Low Risk to Higher Risk Prostate Cancer</brief_title>
  <official_title>Identify Genes/Pathways Responsible for Progression From Low Risk to Higher Risk Prostate Cancer-A New Strategy for Prostate Cancer Prevention</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Taiwan University 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>
      In Taiwan, about 70% of new incident prostate cancer patients have localized disease. Most&#xD;
      patients were detected by PSA screening. Among them, many had low-risk PC, which is very&#xD;
      likely latent in nature, progresses slowly, and rarely leads to death. Most patients died of&#xD;
      other causes, such as other cancers, cardiovascular diseases, and diabetes mellitus. Many&#xD;
      guidelines recommend that active surveillance (AS) or watchful waiting (WW) is a good option&#xD;
      for low risk patients to avoid overtreatment-related complications. However, 30% of patients&#xD;
      on AS will finally need definitive treatments due to disease progression within 10 years. We&#xD;
      hypothesize that there are differential gene expressions between progressive and&#xD;
      non-progressive tumors. If we can identify key genes or pathways that are responsible for&#xD;
      progression of low risk PC to higher risk diseases, PC progression could be reduced&#xD;
      substantially by regulating these genes or pathways and maintain long-term cancer latency to&#xD;
      control non-metastatic PC. In light of the high prevalence rate of latent PC in adult men,&#xD;
      the strategy is in fact the best strategy for preventing clinical PC.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      At the Department of Urology, NTUH, we have established a largest Chinese AS/WW cohort, which&#xD;
      were prospectively collected since 2013. There were already 280 AS and 100 WW patients. Most&#xD;
      AS patients have undergone serial prostate re-biopsies every 1 to 2 years, which is actually&#xD;
      our cutting edge in the field. 87 men had at least twice biopsies at our hospital (mean&#xD;
      interval 15 months). 26 of them showed pathological progression (Group As) who have been&#xD;
      treated aggressively. The other 61 men had no progression even after multiple biopsies (Group&#xD;
      Bs). So, we may compare the genetic changes in each subject in Group A to reveal genetic&#xD;
      changes responsible for progression. We can also compare baseline expressions between Group A&#xD;
      and B to predict progression. We also can correlate genetic alterations in Group A with&#xD;
      cancer phenotypes and short-term post-treatment outcomes.&#xD;
&#xD;
      Here are the four Specific Aims:&#xD;
&#xD;
      Aim-1. To investigate the role of known genes or pathways in mediating progression from low&#xD;
      risk to higher risk by using serial biopsy paraffin embedded tissue blocks from our AS&#xD;
      patients. These known genes/pathways are selected from published reports, which are found to&#xD;
      be related to progression from low to higher grade PC, such as Ki-67, PTEN loss, and&#xD;
      chromosome 8 alterations.&#xD;
&#xD;
      Aim-2. There was only one cDNA microarray gene bank (GSE37199) published in the literature&#xD;
      (Lancet Oncol. 2012; 13:1114) that was associated with differential expression between AS and&#xD;
      mCRPC cohorts. We will proceed with the Gene Set Enrichment Analysis (GSEA) to identify more&#xD;
      potential genes or pathways that have NOT been specifically demonstrated relating to AS&#xD;
      progression. These new genes or pathways will then be studied in Aim-1.&#xD;
&#xD;
      Aim-3. We will perform global cDNA microarray sing non-cancer part of the serial biopsy&#xD;
      paraffin tissue blocks from our AS cohort, followed by GSEA to reveal differential gene&#xD;
      expression between Group A and B patients. Hopefully we can identify genes/pathways that are&#xD;
      related to progression of low risk or latent PC in Taiwanese.&#xD;
&#xD;
      Aim-4. To conduct multivariate analyses considering not only key genetic alterations but also&#xD;
      multiple clinicopathological parameters to build up a model predicting progression from low&#xD;
      to higher risk PC.&#xD;
&#xD;
      In fact, the only one published study (Lancet Oncol. 2012;13:1114) was to reveal differential&#xD;
      cDNA expression in blood cells between AS and mCRPC cohorts, but not between progressive and&#xD;
      non-progressive patients. Therefore, the study design was defective because the obtained&#xD;
      differential expression may not reflect what really happened in low risk cancer progression.&#xD;
      To our knowledge, there has been no differential genetic expression study or the GSEA study&#xD;
      for AS cohort. In addition, we have the largest Taiwanese/Chinese cohort on AS/WW and&#xD;
      abundant serial biopsy specimens. In summary, our study which focuses on genomic research on&#xD;
      AS cohort is a new strategy to prevent clinical PC and is of high novelty and clinical&#xD;
      implications.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 2, 2019</start_date>
  <completion_date type="Anticipated">July 31, 2030</completion_date>
  <primary_completion_date type="Anticipated">July 31, 2030</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>Gene expression</measure>
    <time_frame>3 years</time_frame>
    <description>Using GESA analysis</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Prostate Cancer Stage I</condition>
  <arm_group>
    <arm_group_label>AS cohort with progression</arm_group_label>
    <description>AS cohort with tumor progression</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AS cohort without progression</arm_group_label>
    <description>AS cohort without tumor progression</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Low or intermediate risk prostate cancer patients receiving active surveillance&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Historically or cytologically confirmed adenocarcinoma of prostate.&#xD;
&#xD;
          2. Have or ever received active Surveillance as the main conservative management at NTUH&#xD;
             (National Taiwan University Hospital).&#xD;
&#xD;
          3. Have or will receive prostate biopsy to confirm tumor progression after the diagnosis&#xD;
             of prostate cancer.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Have received systemic chemotherapy, pelvic radiotherapy or androgen deprivation&#xD;
             therapy (ADT) before the obtainment of pathological specimen from prostate operation&#xD;
             or biopsy.&#xD;
&#xD;
          2. Subjects who disagree with signing the informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yeong-Shiau Pu, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Taiwan University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Yeong-Shiau Pu, PhD</last_name>
    <phone>886-2-23123456</phone>
    <phone_ext>65950</phone_ext>
    <email>yspu@ntu.edu.tw</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Chung-Hsin Chen, PhD</last_name>
    <phone>886-2-23123456</phone>
    <phone_ext>65242</phone_ext>
    <email>mufasachen@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>National Taiwan University</name>
      <address>
        <city>Taipei</city>
        <zip>10002</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yeong-Shiau Pu, PhD</last_name>
      <phone>886-2-23123456</phone>
      <phone_ext>65950</phone_ext>
      <email>yspu@ntu.edu.tw</email>
    </contact>
    <contact_backup>
      <last_name>Chung-Hsin Chen, PhD</last_name>
      <phone>886-2-23123456</phone>
      <phone_ext>65242</phone_ext>
      <email>mufasachen@gmail.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>December 26, 2018</study_first_submitted>
  <study_first_submitted_qc>December 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 28, 2018</study_first_posted>
  <last_update_submitted>August 11, 2022</last_update_submitted>
  <last_update_submitted_qc>August 11, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>active surveillance, microarray, latent, GSEA, latent</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic 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/NCT03789253
org study id: 201712093RINB
nct id: NCT03789253
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
In Taiwan, about 70% of new incident prostate cancer patients have localized disease. Most
      patients were detected by PSA screening. Among them, many had low-risk PC, which is very
      likely latent in nature, progresses slowly, and rarely leads to death. Most patients died of
      other causes, such as other cancers, cardiovascular diseases, and diabetes mellitus. Many
      guidelines recommend that active surveillance (AS) or watchful waiting (WW) is a good option
      for low risk patients to avoid overtreatment-related complications. However, 30% of patients
      on AS will finally need definitive treatments due to disease progression within 10 years. We
      hypothesize that there are differential gene expressions between progressive and
      non-progressive tumors. If we can identify key genes or pathways that are responsible for
      progression of low risk PC to higher risk diseases, PC progression could be reduced
      substantially by regulating these genes or pathways and maintain long-term cancer latency to
      control non-metastatic PC. In light of the high prevalence rate of latent PC in adult men,
      the strategy is in fact the best strategy for preventing clinical PC.
At the Department of Urology, NTUH, we have established a largest Chinese AS/WW cohort, which
      were prospectively collected since 2013. There were already 280 AS and 100 WW patients. Most
      AS patients have undergone serial prostate re-biopsies every 1 to 2 years, which is actually
      our cutting edge in the field. 87 men had at least twice biopsies at our hospital (mean
      interval 15 months). 26 of them showed pathological progression (Group As) who have been
      treated aggressively. The other 61 men had no progression even after multiple biopsies (Group
      Bs). So, we may compare the genetic changes in each subject in Group A to reveal genetic
      changes responsible for progression. We can also compare baseline expressions between Group A
      and B to predict progression. We also can correlate genetic alterations in Group A with
      cancer phenotypes and short-term post-treatment outcomes.

      Here are the four Specific Aims:

      Aim-1. To investigate the role of known genes or pathways in mediating progression from low
      risk to higher risk by using serial biopsy paraffin embedded tissue blocks from our AS
      patients. These known genes/pathways are selected from published reports, which are found to
      be related to progression from low to higher grade PC, such as Ki-67, PTEN loss, and
      chromosome 8 alterations.

      Aim-2. There was only one cDNA microarray gene bank (GSE37199) published in the literature
      (Lancet Oncol. 2012; 13:1114) that was associated with differential expression between AS and
      mCRPC cohorts. We will proceed with the Gene Set Enrichment Analysis (GSEA) to identify more
      potential genes or pathways that have NOT been specifically demonstrated relating to AS
      progression. These new genes or pathways will then be studied in Aim-1.

      Aim-3. We will perform global cDNA microarray sing non-cancer part of the serial biopsy
      paraffin tissue blocks from our AS cohort, followed by GSEA to reveal differential gene
      expression between Group A and B patients. Hopefully we can identify genes/pathways that are
      related to progression of low risk or latent PC in Taiwanese.

      Aim-4. To conduct multivariate analyses considering not only key genetic alterations but also
      multiple clinicopathological parameters to build up a model predicting progression from low
      to higher risk PC.

      In fact, the only one published study (Lancet Oncol. 2012;13:1114) was to reveal differential
      cDNA expression in blood cells between AS and mCRPC cohorts, but not between progressive and
      non-progressive patients. Therefore, the study design was defective because the obtained
      differential expression may not reflect what really happened in low risk cancer progression.
      To our knowledge, there has been no differential genetic expression study or the GSEA study
      for AS cohort. In addition, we have the largest Taiwanese/Chinese cohort on AS/WW and
      abundant serial biopsy specimens. In summary, our study which focuses on genomic research on
      AS cohort is a new strategy to prevent clinical PC and is of high novelty and clinical
      implications.
observational model: Cohort
time perspective: Prospective
measure: Gene expression
time frame: 3 years
description: Using GESA analysis
arm group label: AS cohort with progression
description: AS cohort with tumor progression
arm group label: AS cohort without progression
description: AS cohort without tumor progression
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Male
minimum age: 40 Years
maximum age: 100 Years
healthy volunteers: No
last name: Yeong-Shiau Pu, PhD
role: Principal Investigator
affiliation: National Taiwan University
last name: Yeong-Shiau Pu, PhD
phone: 886-2-23123456
phone ext: 65950
email: yspu@ntu.edu.tw
last name: Chung-Hsin Chen, PhD
phone: 886-2-23123456
phone ext: 65242
email: mufasachen@gmail.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: Taiwan
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
sharing ipd: No