<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/NCT03237702</url>
  </required_header>
  <id_info>
    <org_study_id>201705040MIPB</org_study_id>
    <nct_id>NCT03237702</nct_id>
  </id_info>
  <brief_title>Decipher Lethal Prostate Cancer Biology - Urine Metabolomics</brief_title>
  <official_title>Decipher the Biology of Lethal Prostate Cancer - Urine Metabolomics Profiling in Men Receiving Prostate Biopsy and Men With Diagnosed Prostate Cancer Receiving MCS Supplementation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Taipei Medical University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Taipei Veterans General Hospital, Taiwan</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Cardinal Tien Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Taipei Medical University Shuang Ho Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Far Eastern Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Taichung Tzu Chi Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shin Kong Wu Ho-Su Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Chang Gung Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>National Taiwan University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Through a better understanding of the biology of significant (lethal) prostate cancer, we&#xD;
      hope to develop new markers/targets from urine metabolomics for more effective screening and&#xD;
      prevention of significant prostate cancer. In the meantime, with these new markers we may&#xD;
      substantially reduce overtreatment of insignificant PC.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Prostate cancer (PC) afflicts millions of men worldwide. In Taiwan, around 5,000 men are&#xD;
      diagnosed as PC while 1,200 men die of the disease each year. However, thousands of Taiwanese&#xD;
      men may have been over-treated for their insignificant PCs. The above situations signify the&#xD;
      unmet clinical need where effective measures of stratifying risk of PC are lacking. The study&#xD;
      is to identify new markers/targets with which to better screen and prevent significant (sPC)&#xD;
      or lethal PC (lePC).&#xD;
&#xD;
      This is a prospective, observational and investigational study investigating the role of&#xD;
      urine omics studies (metabolomics and proteomics) in subjects who will undergo prostate&#xD;
      biopsy or have completed biopsy and/or subsequent MCS supplementation. MCS (or Botreso) is a&#xD;
      new patented botanic agent, composed of primarily multi-carotenoids, including lycopene,&#xD;
      phytoene, phytofluene, etc. The expected subject number to be enrolled is 620 men and 20&#xD;
      women from NTUH. There will be 3 cohorts: Cohort A (N=990), Cohort B (N=990) and Cohort C&#xD;
      (N=40). Cohort A will be the training cohort used to generate the predictive model. Cohort B&#xD;
      will be the validation cohort used to validate the newly developed predictive model. Cohort C&#xD;
      is the control cohort, including 20 women and 20 men without any signs of cancers.&#xD;
&#xD;
      By risk stratification after biopsy pathology results are available, there will be 5 groups&#xD;
      of subjects, including patients with Group 1. mPC: Metastatic prostate cancer Group 2. sPC:&#xD;
      Non-metastatic significant prostate cancer (sPC) Group 3. isPC: Non-metastatic insignificant&#xD;
      PC (isPC) Group 4. Pre-cancerous lesions: atypical small acinar proliferation (ASAP) or&#xD;
      prostatic intraepithelial neoplasia (PIN) Group 5. Non-cancer benign pathology&#xD;
&#xD;
      Based on NCCN risk classification, sPC is defined as the followings: unfavorable&#xD;
      intermediate-risk, high/very high-risk, or presence of metastasis. The patients with&#xD;
      favorable intermediate-risk prostate cancer will be considered as sPC in the prediction model&#xD;
      in the population with long life expectancy.&#xD;
&#xD;
      Biopsy pathology report and clinicopathological parameters will be recorded. In addition,&#xD;
      transcriptomics study will be performed. Group specific urine omics profiles will be&#xD;
      constructed by comparing the outstanding metabolites between groups. These urine omics&#xD;
      profiles are constructed so as to efficiently separate groups of graded risk stratification,&#xD;
      especially to predict subjects with mPC (Group 1) or sPC (Group 2). The newly constructed&#xD;
      urine omics profiles from Cohort A will be validated against Cohort B of subjects who will&#xD;
      undergo biopsy to determine the predictive efficiency of the constructed profiles.&#xD;
&#xD;
      In Cohort A, sPC (Group 2), isPC (Group 3), ASAP/PIN (Group 4) and benign pathology patients&#xD;
      (Group 5) will further be invited to take MCS supplementation for 8 weeks after the pathology&#xD;
      confirmation. The expected enrollment number is 30 for each of the 4 groups (in total 120).&#xD;
      Urine samples will be collected before and after 8 weeks of MCS supplementation for&#xD;
      metabolomics and proteomics analysis. The effect of MCS supplementation in modifying urine&#xD;
      metabolites will be investigated to determine the potential use of MCS in prostate cancer&#xD;
      chemoprevention.&#xD;
&#xD;
      Through a better understanding of the biology of significant (lethal) PC, we hope to develop&#xD;
      new markers/targets for more effective screening and prevention of sPC. In the meantime, with&#xD;
      these new markers we may substantially reduce overtreatment of insignificant PC.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 1, 2017</start_date>
  <completion_date type="Anticipated">August 1, 2025</completion_date>
  <primary_completion_date type="Anticipated">August 1, 2025</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>
    <intervention_model_description>A total of 1,980 male patients who are planning to have prostate biopsy will be enrolled in the first stage of this study for measuring urine metabolomics. Only the patients who have non-metastatic significant prostate cancer, insignificant prostate cancer, ASAP/PIN, or benign prostate proved by prostate biopsy are enrolled into the second stage in which MCS supplementation will be used for 8 weeks.&#xD;
In addition, 20 men and 20 women will be enrolled as a healthy control without any further medication.</intervention_model_description>
    <primary_purpose>Screening</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change of urine metabolomics</measure>
    <time_frame>8 weeks</time_frame>
    <description>Observe the change of metabolomics in urine samples collected before and upon the completeness of MCS supplementation</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">2000</enrollment>
  <condition>Significant Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>MCS arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The participants who will have Multi-Carotenoids for 8 weeks The intervention is Multi-Carotenoids 30 mg for 8 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Multi-Carotenoids</intervention_name>
    <description>All participants in the second stage will receive multi-carotenoids 30 mg qd for 8 weeks.</description>
    <arm_group_label>MCS arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subjects who have planned to undergo prostate biopsy or have completed biopsy before 6&#xD;
             weeks.&#xD;
&#xD;
          2. Subjects who are aged between 30 and 100 years men.&#xD;
&#xD;
          3. For subjects who are prostate cancer patients for rebiopsy, the testosterone level&#xD;
             should be within normal limit (testosterone &gt;1.5 ng/ml).&#xD;
&#xD;
          4. Subjects who understand the entire study procedures and consent to donate his spot&#xD;
             urine (once for 50 ml) and agree with subsequent analyses of his clinical information&#xD;
             including biopsy results, treatments and outcomes. (Note: Subjects will be told that&#xD;
             the urine metabolomics results will not be revealed to them.)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects who have other active cancers. However, subjects who have cancers that have&#xD;
             been curatively treated and who are disease-free for 3 years or longer are allowed to&#xD;
             be enrolled.&#xD;
&#xD;
          2. Subjects who have severe organ function impairment which may significantly alter&#xD;
             general cell metabolism determined by the investigators, such as or Cre &gt; 3.0, HbA1c &gt;&#xD;
             9.0%, symptomatic heart failure, or other symptomatic metabolic diseases.&#xD;
&#xD;
          3. Subjects who are receiving or have received systemic therapy, such as chemotherapy,&#xD;
             androgen deprivation therapy (ADT), immunotherapy, or targeted therapy within 3 months&#xD;
             of the screening.&#xD;
&#xD;
          4. Subjects who have been treated with pelvic radiotherapy within 3 months of the&#xD;
             screening.&#xD;
&#xD;
          5. Subjects who have significant infection or inflammation within 8 weeks of the biopsy.&#xD;
&#xD;
          6. Subjects who have pyuria (defined as &gt; 5 WBC/HPF) of urinalysis results within 4 weeks&#xD;
             of the biopsy&#xD;
&#xD;
          7. Topical or oral prednisolone equivalent dosage larger 10 mg per day for 14 days or&#xD;
             more.&#xD;
&#xD;
          8. The last dose of prednisolone is within 4 weeks of the biopsy.&#xD;
&#xD;
          9. Subjects who have a life expectancy less than 12 months.&#xD;
&#xD;
         10. Subjects who use MCS or found supplementation containing large amount of lycopene in&#xD;
             recent 60 days or less. The definition of large amount of lycopene is more than 2 mg&#xD;
             per day.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yeong-Shiau Pu, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Urology, National Taiwan University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Chung-Hsin Chen, MD PhD</last_name>
    <phone>+886-23123456</phone>
    <phone_ext>65242</phone_ext>
    <email>mufasachen@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Yeong-Shiau Pu, MD PhD</last_name>
    <phone>+886-23123456</phone>
    <phone_ext>65254</phone_ext>
    <email>pu5249@ntuh.gov.tw</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Department of Urology, National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Chung-Hsin Chen, MD PhD</last_name>
      <phone>886-2-23123456</phone>
      <phone_ext>65242</phone_ext>
      <email>mufasachen@gmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Yeong-Shiau Pu, MD PhD</last_name>
      <phone>886-2-23123456</phone>
      <phone_ext>65254</phone_ext>
      <email>pu5249@ntuh.gov.tw</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>July 31, 2017</study_first_submitted>
  <study_first_submitted_qc>August 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 2, 2017</study_first_posted>
  <last_update_submitted>December 5, 2022</last_update_submitted>
  <last_update_submitted_qc>December 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 7, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>prostate cancer</keyword>
  <keyword>prostate biopsy</keyword>
  <keyword>biomarkers</keyword>
  <keyword>metabolomics</keyword>
  <keyword>overtreatment</keyword>
  <keyword>cancer screening</keyword>
  <keyword>urine</keyword>
  <keyword>lycopene</keyword>
  <keyword>proteomics</keyword>
  <keyword>urine omics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carotenoids</mesh_term>
  </intervention_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/NCT03237702
org study id: 201705040MIPB
nct id: NCT03237702
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Through a better understanding of the biology of significant (lethal) prostate cancer, we
      hope to develop new markers/targets from urine metabolomics for more effective screening and
      prevention of significant prostate cancer. In the meantime, with these new markers we may
      substantially reduce overtreatment of insignificant PC.
Prostate cancer (PC) afflicts millions of men worldwide. In Taiwan, around 5,000 men are
      diagnosed as PC while 1,200 men die of the disease each year. However, thousands of Taiwanese
      men may have been over-treated for their insignificant PCs. The above situations signify the
      unmet clinical need where effective measures of stratifying risk of PC are lacking. The study
      is to identify new markers/targets with which to better screen and prevent significant (sPC)
      or lethal PC (lePC).

      This is a prospective, observational and investigational study investigating the role of
      urine omics studies (metabolomics and proteomics) in subjects who will undergo prostate
      biopsy or have completed biopsy and/or subsequent MCS supplementation. MCS (or Botreso) is a
      new patented botanic agent, composed of primarily multi-carotenoids, including lycopene,
      phytoene, phytofluene, etc. The expected subject number to be enrolled is 620 men and 20
      women from NTUH. There will be 3 cohorts: Cohort A (N=990), Cohort B (N=990) and Cohort C
      (N=40). Cohort A will be the training cohort used to generate the predictive model. Cohort B
      will be the validation cohort used to validate the newly developed predictive model. Cohort C
      is the control cohort, including 20 women and 20 men without any signs of cancers.

      By risk stratification after biopsy pathology results are available, there will be 5 groups
      of subjects, including patients with Group 1. mPC: Metastatic prostate cancer Group 2. sPC:
      Non-metastatic significant prostate cancer (sPC) Group 3. isPC: Non-metastatic insignificant
      PC (isPC) Group 4. Pre-cancerous lesions: atypical small acinar proliferation (ASAP) or
      prostatic intraepithelial neoplasia (PIN) Group 5. Non-cancer benign pathology

      Based on NCCN risk classification, sPC is defined as the followings: unfavorable
      intermediate-risk, high/very high-risk, or presence of metastasis. The patients with
      favorable intermediate-risk prostate cancer will be considered as sPC in the prediction model
      in the population with long life expectancy.

      Biopsy pathology report and clinicopathological parameters will be recorded. In addition,
      transcriptomics study will be performed. Group specific urine omics profiles will be
      constructed by comparing the outstanding metabolites between groups. These urine omics
      profiles are constructed so as to efficiently separate groups of graded risk stratification,
      especially to predict subjects with mPC (Group 1) or sPC (Group 2). The newly constructed
      urine omics profiles from Cohort A will be validated against Cohort B of subjects who will
      undergo biopsy to determine the predictive efficiency of the constructed profiles.

      In Cohort A, sPC (Group 2), isPC (Group 3), ASAP/PIN (Group 4) and benign pathology patients
      (Group 5) will further be invited to take MCS supplementation for 8 weeks after the pathology
      confirmation. The expected enrollment number is 30 for each of the 4 groups (in total 120).
      Urine samples will be collected before and after 8 weeks of MCS supplementation for
      metabolomics and proteomics analysis. The effect of MCS supplementation in modifying urine
      metabolites will be investigated to determine the potential use of MCS in prostate cancer
      chemoprevention.

      Through a better understanding of the biology of significant (lethal) PC, we hope to develop
      new markers/targets for more effective screening and prevention of sPC. In the meantime, with
      these new markers we may substantially reduce overtreatment of insignificant PC.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: A total of 1,980 male patients who are planning to have prostate biopsy will be enrolled in the first stage of this study for measuring urine metabolomics. Only the patients who have non-metastatic significant prostate cancer, insignificant prostate cancer, ASAP/PIN, or benign prostate proved by prostate biopsy are enrolled into the second stage in which MCS supplementation will be used for 8 weeks.
In addition, 20 men and 20 women will be enrolled as a healthy control without any further medication.
primary purpose: Screening
masking: None (Open Label)
measure: Change of urine metabolomics
time frame: 8 weeks
description: Observe the change of metabolomics in urine samples collected before and upon the completeness of MCS supplementation
arm group label: MCS arm
arm group type: Experimental
description: The participants who will have Multi-Carotenoids for 8 weeks The intervention is Multi-Carotenoids 30 mg for 8 weeks.
intervention type: Dietary Supplement
intervention name: Multi-Carotenoids
description: All participants in the second stage will receive multi-carotenoids 30 mg qd for 8 weeks.
arm group label: MCS arm
criteria: 
gender: Male
minimum age: 30 Years
maximum age: 100 Years
healthy volunteers: No
last name: Yeong-Shiau Pu, MD PhD
role: Principal Investigator
affiliation: Department of Urology, National Taiwan University Hospital
last name: Chung-Hsin Chen, MD PhD
phone: +886-23123456
phone ext: 65242
email: mufasachen@gmail.com
last name: Yeong-Shiau Pu, MD PhD
phone: +886-23123456
phone ext: 65254
email: pu5249@ntuh.gov.tw
facility: 
status: Recruiting
contact: 
contact backup: 
country: Taiwan
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Carotenoids
sharing ipd: No