<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/NCT03236688</url>
  </required_header>
  <id_info>
    <org_study_id>ECT2015-004</org_study_id>
    <nct_id>NCT03236688</nct_id>
  </id_info>
  <brief_title>Detection of ARv7 in the Plasma of Men With Advanced Metastatic Castrate Resistant Prostate Cancer (MCRP)</brief_title>
  <official_title>Detection of ARv7 in the Plasma of Men With Advanced Metastatic Castrate Resistant Prostate Cancer (MCRP)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Exosome Diagnostics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Exosome Diagnostics, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Demonstrate detection of ARv7 splice variant transcripts from exosomes in the circulation of&#xD;
      MCRPC patients pre and post treatment with selective Androgen pathway inhibitors (i.e.&#xD;
      abiraterone and enzalutamide)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Objective&#xD;
&#xD;
      -Demonstrate detection of ARv7 splice variant transcripts from exosomes in the circulation of&#xD;
      MCRPC patients pre and post treatment with selective Androgen pathway inhibitors (i.e.&#xD;
      abiraterone and enzalutamide)&#xD;
&#xD;
      Secondary and Exploratory Objectives&#xD;
&#xD;
        -  Correlate ARv7 status with PSA response (&gt;/=50% decline in PSA level from baseline,&#xD;
           maintained for &gt;/=4 weeks) at any time after the initiation of therapy.&#xD;
&#xD;
        -  Comparison of median progression free survival (PFS) and overall survival (OS).&#xD;
&#xD;
        -  Determine additional molecular lesions in exoRNA and cfDNA in MCRPC patients&#xD;
           post-treatment with androgen pathway inhibitors.&#xD;
&#xD;
        -  Correlate other AR-variants (non ARv7) with clinical outcomes including PSA response.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Suspended</overall_status>
  <start_date>February 2016</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2024</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>Detection of ARv7 splice variant in the circulation of MCRPC patients. PSA response rate in ARv7 positive patients.</measure>
    <time_frame>Two years</time_frame>
    <description>The detection of ARv7 splice variants in samples will be considered both binary: positive or negative/not assessable and level based. ARv7 splice variants from exosomes will be detectable from baseline in 50% of both API; PSA response rates will be 10% or less in ARv7 positive patients. With a sample of 30 patients (as reported in the NEJM study) per cohort would allow the study to have an 85% power to detect a difference of 50 percentage points in PSA response rates, with the use of a two-sided test at an alpha level of 0.1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Detection of ARv7 splice variant in the circulation of MCRPC patients. PSA response rate in ARv7 negative patients.</measure>
    <time_frame>Two years</time_frame>
    <description>The detection of ARv7 splice variants in samples will be considered both binary: positive or negative/not assessable and level based. ARv7 splice variants from exosomes will be detectable from baseline in 50% of both API; PSA response rates will be 50% or more in ARv7 negative patients. With a sample of 30 patients (as reported in the NEJM study) per cohort would allow the study to have an 85% power to detect a difference of 50 percentage points in PSA response rates, with the use of a two-sided test at an alpha level of 0.1.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Metastatic Castrate Resistant Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>MCRPC</arm_group_label>
    <description>Metastatic Castrate Resistant Prostate Cancer (MCRPC) Patients</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      10-20 mL of whole blood collected in K2EDTA Plasma Preparation Tubes (PPT) will be acquired&#xD;
      via standard venipuncture and processed to plasma.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Community sample&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Participants must have histologically confirmed diagnosis of adenocarcinoma of the&#xD;
             prostate.&#xD;
&#xD;
          2. Clinical or radiographic evidence of metastatic disease.&#xD;
&#xD;
          3. Planned therapy with either enzalutamide or abiraterone acetate within the coming 6&#xD;
             weeks.&#xD;
&#xD;
          4. Evidence of disease progression on or following most recent therapy as evidenced by&#xD;
             the following:&#xD;
&#xD;
               -  Radiographic evidence of disease progression as defined by one or more new bone&#xD;
                  scan lesions.&#xD;
&#xD;
               -  Growth of soft tissue / visceral metastases to greater than one centimeter in&#xD;
                  longest diameter.&#xD;
&#xD;
               -  Progressive disease despite 'castration levels' of serum testosterone (&lt;50ng/dL&#xD;
                  with continued androgen deprivation therapy.&#xD;
&#xD;
          5. At least two of the following high risk features during screening for rapid disease&#xD;
             progression:&#xD;
&#xD;
               -  Anemia with a hemoglobin &lt;12.0 g/dL&#xD;
&#xD;
               -  Elevated alkaline phosphatase&#xD;
&#xD;
               -  High lactate dehydrogenase (LDH)&#xD;
&#xD;
               -  Presence of visceral metastasis on imaging&#xD;
&#xD;
               -  Presence of clinically significant pain requiring opioid analgesics.&#xD;
&#xD;
               -  PSA doubling time under 3 months on most recent therapy&#xD;
&#xD;
               -  PSA values obtained 2 or more weeks apart, with last value being 2.0ng/mL or&#xD;
                  higher.&#xD;
&#xD;
          6. Ability to understand and willingness to sign a written informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Receiving or intend to receive concurrent chemotherapy&#xD;
&#xD;
          2. Hepatitis (all types) in patient's medical record&#xD;
&#xD;
          3. HIV documented in patient's medical record&#xD;
&#xD;
          4. History of intercurrent or past medical history or psychiatric illness that would make&#xD;
             participation in a blood drawing protocol difficult or not feasible.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Roger Tun</last_name>
    <role>Study Director</role>
    <affiliation>Exosome Diagnostics, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Yale University School of Medicine</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>February 23, 2016</study_first_submitted>
  <study_first_submitted_qc>July 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 2, 2017</study_first_posted>
  <last_update_submitted>October 5, 2022</last_update_submitted>
  <last_update_submitted_qc>October 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 6, 2022</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>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03236688
org study id: ECT2015-004
nct id: NCT03236688
lead sponsor: 
collaborator: 
has dmc: No
Demonstrate detection of ARv7 splice variant transcripts from exosomes in the circulation of
      MCRPC patients pre and post treatment with selective Androgen pathway inhibitors (i.e.
      abiraterone and enzalutamide)
Primary Objective

      -Demonstrate detection of ARv7 splice variant transcripts from exosomes in the circulation of
      MCRPC patients pre and post treatment with selective Androgen pathway inhibitors (i.e.
      abiraterone and enzalutamide)

      Secondary and Exploratory Objectives

        -  Correlate ARv7 status with PSA response (>/=50% decline in PSA level from baseline,
           maintained for >/=4 weeks) at any time after the initiation of therapy.

        -  Comparison of median progression free survival (PFS) and overall survival (OS).

        -  Determine additional molecular lesions in exoRNA and cfDNA in MCRPC patients
           post-treatment with androgen pathway inhibitors.

        -  Correlate other AR-variants (non ARv7) with clinical outcomes including PSA response.
observational model: Cohort
time perspective: Prospective
measure: Detection of ARv7 splice variant in the circulation of MCRPC patients. PSA response rate in ARv7 positive patients.
time frame: Two years
description: The detection of ARv7 splice variants in samples will be considered both binary: positive or negative/not assessable and level based. ARv7 splice variants from exosomes will be detectable from baseline in 50% of both API; PSA response rates will be 10% or less in ARv7 positive patients. With a sample of 30 patients (as reported in the NEJM study) per cohort would allow the study to have an 85% power to detect a difference of 50 percentage points in PSA response rates, with the use of a two-sided test at an alpha level of 0.1.
measure: Detection of ARv7 splice variant in the circulation of MCRPC patients. PSA response rate in ARv7 negative patients.
time frame: Two years
description: The detection of ARv7 splice variants in samples will be considered both binary: positive or negative/not assessable and level based. ARv7 splice variants from exosomes will be detectable from baseline in 50% of both API; PSA response rates will be 50% or more in ARv7 negative patients. With a sample of 30 patients (as reported in the NEJM study) per cohort would allow the study to have an 85% power to detect a difference of 50 percentage points in PSA response rates, with the use of a two-sided test at an alpha level of 0.1.
arm group label: MCRPC
description: Metastatic Castrate Resistant Prostate Cancer (MCRPC) Patients
10-20 mL of whole blood collected in K2EDTA Plasma Preparation Tubes (PPT) will be acquired
      via standard venipuncture and processed to plasma.
study pop: 
sampling method: Probability Sample
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Roger Tun
role: Study Director
affiliation: Exosome Diagnostics, Inc.
facility: 
country: United States
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
sharing ipd: Undecided