<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/NCT04403568</url>
  </required_header>
  <id_info>
    <org_study_id>HSC20190735H</org_study_id>
    <nct_id>NCT04403568</nct_id>
  </id_info>
  <brief_title>Testing the Synergism of Phytonutrients, Curcumin and Ursolic Acid, to Target Molecular Pathways in the Prostate</brief_title>
  <official_title>Phase I Clinical Trial Testing the Synergism of Phytonutrients, Curcumin and Ursolic Acid, to Target Molecular Pathways in the Prostate</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Texas Health Science Center at San Antonio</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The University of Texas Health Science Center at San Antonio</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      A proof of concept clinical trial to assess the synergism of curcumin (CURC) and ursolic acid&#xD;
      (UA). Before further testing within formal cancer clinical trials, we must (1) evaluate the&#xD;
      bioavailability and safety, (2) confirm the presence of metabolites in the target organ, and&#xD;
      (3) validate the appropriate mechanism of effect&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Once a subject is identified that may meet eligibility criteria, the physician and/or study&#xD;
      investigators will be alerted to the potential candidate and will introduce the study to the&#xD;
      patient at their standard of care (SOC) appointment or via telephone. Patients will be given&#xD;
      the option for enrollment and if they agree, informed consent will be discussed and obtained&#xD;
      provided they meet all inclusion/exclusion criteria. Following informed consent, subjects&#xD;
      will be assigned to one of the following cohorts:&#xD;
&#xD;
      Cohort 1:&#xD;
&#xD;
      • Ursolic Acid (150 mg) BID (twice a day)&#xD;
&#xD;
      Cohort 2:&#xD;
&#xD;
      • Curcumin (600 mg) BID&#xD;
&#xD;
      Cohort 3:&#xD;
&#xD;
      • Ursolic Acid (150 mg) and Curcumin (600 mg) BID&#xD;
&#xD;
      The study team aim to enroll 10 subjects who will complete the study into each cohort for a&#xD;
      total of 30 completers. Subjects will be enrolled on a rolling basis with the first ten&#xD;
      subjects assigned to Cohort 1, the next ten subjects assigned to Cohort 2, and the last 10&#xD;
      subjects assigned to Cohort 3.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No subjects were enrolled in this study, the PI will seek funding and revise the protocol for&#xD;
    resubmisson at a later date&#xD;
  </why_stopped>
  <start_date type="Anticipated">October 2021</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2022</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Subjects will be assigned to one of 3 cohorts, starting with cohort 1 and progressing to cohort 3</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number, frequency, duration, and relation of toxicity events</measure>
    <time_frame>Baseline to 8 weeks</time_frame>
    <description>Safety will be compared to evaluate the number, frequency, duration, and relation of toxicity events to CURC/UA combination, as defined by the Common Terminology Criteria for Adverse Events (CTCAE) v 4.03.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Peak serum concentration</measure>
    <time_frame>Baseline to 8 weeks</time_frame>
    <description>Dose response curve representing the pharmacokinetic parameter peak serum concentration (Cmax) of ursolic acid, curcumin, and their metabolites will be graphed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to reach peak serum concentration</measure>
    <time_frame>Baseline to 8 weeks</time_frame>
    <description>The pharmacokinetic parameter, the area under the curve (Tmax) representing the time it takes to reach Cmax of ursolic acid, curcumin, and their metabolites will be graphed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Half-life</measure>
    <time_frame>Baseline to 8 weeks</time_frame>
    <description>The pharmacokinetic parameter, half-life of ursolic acid, curcumin, and their metabolites will be graphed.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Levels of UA, CURC, and metabolites in prostate tissue</measure>
    <time_frame>Baseline to 8 weeks</time_frame>
    <description>Identify the presence and levels of UA, CURC and their metabolites in prostate tissue using HPLC.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunohistochemistry measurement</measure>
    <time_frame>Baseline to 8 weeks</time_frame>
    <description>Immunohistochemistry of proportion of nuclear p65 NFkB staining before and after prostatectomy on FFPE samples will be completed.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Ursolic Acid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Administration of Ursolic Acid to subjects who are scheduled to undergo radical prostatectomy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Curcumin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Administration of Curcumin to subjects who are scheduled to undergo radical prostatectomy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ursolic Acid and Curcumin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Administration of Ursolic Acid and Curcumin to subjects who are scheduled to undergo radical prostatectomy</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ursolic Acid</intervention_name>
    <description>Ursolic Acid 150mg</description>
    <arm_group_label>Ursolic Acid</arm_group_label>
    <arm_group_label>Ursolic Acid and Curcumin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Curcumin</intervention_name>
    <description>Curcumin 600mg</description>
    <arm_group_label>Curcumin</arm_group_label>
    <arm_group_label>Ursolic Acid and Curcumin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Have proven diagnosis of prostate cancer with Gleason Group 3 or lower and planning to&#xD;
             undergo radical prostatectomy&#xD;
&#xD;
          -  Be able to give informed consent&#xD;
&#xD;
          -  Be age 18 or older&#xD;
&#xD;
          -  Able to stop supplements&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unable to give informed consent&#xD;
&#xD;
          -  Age &lt; 18&#xD;
&#xD;
          -  High-risk prostate cancer or suspected metastasis&#xD;
&#xD;
          -  Unable to swallow pills&#xD;
&#xD;
          -  Unable to stop supplements&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael A Liss, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Texas Health at San Antonio</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mays Cancer Center</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>May 21, 2020</study_first_submitted>
  <study_first_submitted_qc>May 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 27, 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>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Radical Prostatectomy</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>Ursolic acid</mesh_term>
    <mesh_term>Curcumin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>De-identified individual participant data will be available upon request.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>De-identified individual participant data will be available upon completion of the study for approx. 1 year.</ipd_time_frame>
    <ipd_access_criteria>Access granted upon request.</ipd_access_criteria>
  </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/NCT04403568
org study id: HSC20190735H
nct id: NCT04403568
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
A proof of concept clinical trial to assess the synergism of curcumin (CURC) and ursolic acid
      (UA). Before further testing within formal cancer clinical trials, we must (1) evaluate the
      bioavailability and safety, (2) confirm the presence of metabolites in the target organ, and
      (3) validate the appropriate mechanism of effect
Once a subject is identified that may meet eligibility criteria, the physician and/or study
      investigators will be alerted to the potential candidate and will introduce the study to the
      patient at their standard of care (SOC) appointment or via telephone. Patients will be given
      the option for enrollment and if they agree, informed consent will be discussed and obtained
      provided they meet all inclusion/exclusion criteria. Following informed consent, subjects
      will be assigned to one of the following cohorts:

      Cohort 1:

      • Ursolic Acid (150 mg) BID (twice a day)

      Cohort 2:

      • Curcumin (600 mg) BID

      Cohort 3:

      • Ursolic Acid (150 mg) and Curcumin (600 mg) BID

      The study team aim to enroll 10 subjects who will complete the study into each cohort for a
      total of 30 completers. Subjects will be enrolled on a rolling basis with the first ten
      subjects assigned to Cohort 1, the next ten subjects assigned to Cohort 2, and the last 10
      subjects assigned to Cohort 3.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: Subjects will be assigned to one of 3 cohorts, starting with cohort 1 and progressing to cohort 3
primary purpose: Basic Science
masking: None (Open Label)
measure: Number, frequency, duration, and relation of toxicity events
time frame: Baseline to 8 weeks
description: Safety will be compared to evaluate the number, frequency, duration, and relation of toxicity events to CURC/UA combination, as defined by the Common Terminology Criteria for Adverse Events (CTCAE) v 4.03.
measure: Peak serum concentration
time frame: Baseline to 8 weeks
description: Dose response curve representing the pharmacokinetic parameter peak serum concentration (Cmax) of ursolic acid, curcumin, and their metabolites will be graphed.
measure: Time to reach peak serum concentration
time frame: Baseline to 8 weeks
description: The pharmacokinetic parameter, the area under the curve (Tmax) representing the time it takes to reach Cmax of ursolic acid, curcumin, and their metabolites will be graphed.
measure: Half-life
time frame: Baseline to 8 weeks
description: The pharmacokinetic parameter, half-life of ursolic acid, curcumin, and their metabolites will be graphed.
measure: Levels of UA, CURC, and metabolites in prostate tissue
time frame: Baseline to 8 weeks
description: Identify the presence and levels of UA, CURC and their metabolites in prostate tissue using HPLC.
measure: Immunohistochemistry measurement
time frame: Baseline to 8 weeks
description: Immunohistochemistry of proportion of nuclear p65 NFkB staining before and after prostatectomy on FFPE samples will be completed.
arm group label: Ursolic Acid
arm group type: Experimental
description: Administration of Ursolic Acid to subjects who are scheduled to undergo radical prostatectomy
arm group label: Curcumin
arm group type: Experimental
description: Administration of Curcumin to subjects who are scheduled to undergo radical prostatectomy
arm group label: Ursolic Acid and Curcumin
arm group type: Experimental
description: Administration of Ursolic Acid and Curcumin to subjects who are scheduled to undergo radical prostatectomy
intervention type: Drug
intervention name: Ursolic Acid
description: Ursolic Acid 150mg
arm group label: Ursolic Acid
arm group label: Ursolic Acid and Curcumin
intervention type: Drug
intervention name: Curcumin
description: Curcumin 600mg
arm group label: Curcumin
arm group label: Ursolic Acid and Curcumin
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michael A Liss, MD
role: Principal Investigator
affiliation: University of Texas Health at San Antonio
facility: 
country: United States
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Ursolic acid
mesh term: Curcumin
sharing ipd: Yes
ipd description: De-identified individual participant data will be available upon request.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: De-identified individual participant data will be available upon completion of the study for approx. 1 year.
ipd access criteria: Access granted upon request.