<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/NCT04473833</url>
  </required_header>
  <id_info>
    <org_study_id>MCC-88-GYN-13</org_study_id>
    <nct_id>NCT04473833</nct_id>
  </id_info>
  <brief_title>Transvaginal Ultrasonography as a Screening Method for Ovarian Cancer</brief_title>
  <official_title>Transvaginal Ultrasonography as a Screening Method for Ovarian Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>John R van Nagell</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Kentucky</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a large, prospective, single-arm cohort study of transvaginal ultrasonographic&#xD;
      screening for ovarian cancer in intermediate to high-risk women from Kentucky. Detection of&#xD;
      ovarian malignancy often occurs subsequent to the initial transvaginal sonography (TVS)&#xD;
      screen; therefore, it is important to offer continued screening to study participants based&#xD;
      on our published algorithm. Screening will be available to participants for as long as they&#xD;
      elect to receive it. The primary study endpoints are to determine if prospective serial&#xD;
      transvaginal ultrasonography can decrease the false-positive (FP) percentage and improve the&#xD;
      positive predictive value (PPV) as suggested by retrospective analysis without compromising&#xD;
      the detection of true positives or promote the occurrence of false negatives.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Women from every Kentucky county participate in the Kentucky Ovarian Cancer Screening&#xD;
      Program. Screening sites include: Maysville, Prestonsburg, Greenup, Elizabethtown, Somerset,&#xD;
      Paducah and Lexington. Offsite participants account for 14% of the screening population with&#xD;
      86% being screened in Lexington. The long-term survival (20 year) of women with&#xD;
      screen-detected ovarian cancers is twice that of unscreened women (65% vs 32%). Separation of&#xD;
      cases into Type 1 and Type 2 ovarian cancer shows that screening improves the survival of&#xD;
      both Type 1 and Type 2 ovarian cancers. Type 1 ovarian carcinomas for the screened and&#xD;
      unscreened populations were defined based on these WHO criteria: mucinous carcinomas all&#xD;
      grade, clear cell carcinomas all grades, endometrioid carcinomas grades 1 &amp; 2, serous&#xD;
      carcinomas grades 1 &amp; 2, and malignant Brenner's tumors all grades. Type 2 ovarian carcinomas&#xD;
      for the screened and unscreened populations were defined based on these criteria:&#xD;
      undifferentiated carcinomas, endometrioid carcinomas grade 3, serous carcinomas grade 3, and&#xD;
      carcinosarcomas.&#xD;
&#xD;
      While long-term 20-year survival of women with Type 1 ovarian cancers detected by screening&#xD;
      was significantly better than for unscreened women (81% v 46%, respectively), the survival&#xD;
      benefit was even more pronounced for Type 2 ovarian cancers detected by screening of Kentucky&#xD;
      women compared to unscreened Kentucky women (55.7% vs. 0.3%, respectively) or unscreened&#xD;
      women at UK Hospital (12%). Screen-detected cases of Type 2 invasive ovarian cancers had&#xD;
      better survival than unscreened cases when those detected had early- or late-stage disease.&#xD;
      However, better survival was achieved when Type 2 ovarian cancers were detected at an early&#xD;
      (72%) compared to late-stage (46%). Our data support the effectiveness of the screening&#xD;
      protocol at the University of Kentucky, and subsequent treatment in accordance with National&#xD;
      Comprehensive Cancer Network guidelines.&#xD;
&#xD;
      The significance of these findings is that our approach has resulted in the detection of both&#xD;
      early-stage Type 1 and Type 2 ovarian cancers and these cases have had improved survival when&#xD;
      compared to that of unscreened cases, indicating that the screen-detected cases are&#xD;
      associated with a potential survival advantage even for aggressive ovarian carcinomas.&#xD;
&#xD;
      The primary objective of this study is to prospectively evaluate the false positive (FP)&#xD;
      percentage generated by the ovarian screening algorithm and determine whether serial&#xD;
      transvaginal ultrasonography can lower the FP percentage as demonstrated in the retrospective&#xD;
      analysis. The aim of serial ultrasonography is to decrease FP percentage to 0.32% (positive&#xD;
      predictive value of 24%) without adversely impacting the results for true positives and false&#xD;
      negatives. on a &quot;per woman screened basis&quot; since this corresponds to a minimally acceptable&#xD;
      positive predictive value of 24% or higher. This assumes an average of three screening years&#xD;
      for each new woman entering the program.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 19, 1988</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2024</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>
    <primary_purpose>Screening</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>False-positive (FP) percentage</measure>
    <time_frame>approximately 3 years</time_frame>
    <description>Measure the false-positive (FP) rate generated by the ovarian screening algorithm.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">58000</enrollment>
  <condition>Ovarian Cancer</condition>
  <arm_group>
    <arm_group_label>Participants in the Kentucky Ovarian Cancer Screening Program</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants from the Kentucky Ovarian Cancer Screening Program who choose to participate in this trial will undergo further serial transvaginal ultrasonography (TVS) screening.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Serial Transvaginal Ultrasonography</intervention_name>
    <description>Participants will undergo transvaginal ultrasonography (TVS) to detect ovarian cancer as part of the Kentucky Ovarian Cancer Screening Program. Those with normal findings will repeat the TVS in one year. Those with abnormal results will repeat the screening in 4-6 weeks.</description>
    <arm_group_label>Participants in the Kentucky Ovarian Cancer Screening Program</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  women over the age of 50 years;&#xD;
&#xD;
          -  women with a documented family history of ovarian cancer over the age of 24 years;&#xD;
&#xD;
          -  women over the age of 24 years with a personal history of breast cancer&#xD;
&#xD;
          -  ECOG performance status of 0 to 2.34&#xD;
&#xD;
          -  Subjects having undergone prior hysterectomy will be eligible provided that they meet&#xD;
             the other requirements for entry into this study and have at least one ovary.&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women who are referred with pelvic symptoms, a known pelvic mass or a history of prior&#xD;
             radiation.&#xD;
&#xD;
          -  Individuals that cannot safely receive transvaginal ultrasound due to vaginal size,&#xD;
             vaginal infections, lack of bowel or bladder control or inability to physically place&#xD;
             their body in position to receive transvaginal ultrasound&#xD;
&#xD;
          -  Prisoners&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  Women with a prior history of ovarian cancer&#xD;
&#xD;
          -  Exclusions will apply to anyone who presents with factors or issues that prevent them&#xD;
             from understanding the screening research procedures or completing the informed&#xD;
             consent component or personal information needed for the study&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>24 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John R Van Nagell</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Kentucky</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Tina Payne</last_name>
    <phone>859-323-4687</phone>
    <email>tcpayne@uky.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Markey Cancer Center</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>John R Van Nagell</last_name>
    </contact>
    <investigator>
      <last_name>John Villano, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>July 13, 2020</study_first_submitted>
  <study_first_submitted_qc>July 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 16, 2020</study_first_posted>
  <last_update_submitted>November 1, 2022</last_update_submitted>
  <last_update_submitted_qc>November 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Kentucky</investigator_affiliation>
    <investigator_full_name>John R van Nagell</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>serial</keyword>
  <keyword>transvaginal ultrasonography</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ovarian Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Ovarian Epithelial</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/NCT04473833
org study id: MCC-88-GYN-13
nct id: NCT04473833
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is a large, prospective, single-arm cohort study of transvaginal ultrasonographic
      screening for ovarian cancer in intermediate to high-risk women from Kentucky. Detection of
      ovarian malignancy often occurs subsequent to the initial transvaginal sonography (TVS)
      screen; therefore, it is important to offer continued screening to study participants based
      on our published algorithm. Screening will be available to participants for as long as they
      elect to receive it. The primary study endpoints are to determine if prospective serial
      transvaginal ultrasonography can decrease the false-positive (FP) percentage and improve the
      positive predictive value (PPV) as suggested by retrospective analysis without compromising
      the detection of true positives or promote the occurrence of false negatives.
Women from every Kentucky county participate in the Kentucky Ovarian Cancer Screening
      Program. Screening sites include: Maysville, Prestonsburg, Greenup, Elizabethtown, Somerset,
      Paducah and Lexington. Offsite participants account for 14% of the screening population with
      86% being screened in Lexington. The long-term survival (20 year) of women with
      screen-detected ovarian cancers is twice that of unscreened women (65% vs 32%). Separation of
      cases into Type 1 and Type 2 ovarian cancer shows that screening improves the survival of
      both Type 1 and Type 2 ovarian cancers. Type 1 ovarian carcinomas for the screened and
      unscreened populations were defined based on these WHO criteria: mucinous carcinomas all
      grade, clear cell carcinomas all grades, endometrioid carcinomas grades 1 & 2, serous
      carcinomas grades 1 & 2, and malignant Brenner's tumors all grades. Type 2 ovarian carcinomas
      for the screened and unscreened populations were defined based on these criteria:
      undifferentiated carcinomas, endometrioid carcinomas grade 3, serous carcinomas grade 3, and
      carcinosarcomas.

      While long-term 20-year survival of women with Type 1 ovarian cancers detected by screening
      was significantly better than for unscreened women (81% v 46%, respectively), the survival
      benefit was even more pronounced for Type 2 ovarian cancers detected by screening of Kentucky
      women compared to unscreened Kentucky women (55.7% vs. 0.3%, respectively) or unscreened
      women at UK Hospital (12%). Screen-detected cases of Type 2 invasive ovarian cancers had
      better survival than unscreened cases when those detected had early- or late-stage disease.
      However, better survival was achieved when Type 2 ovarian cancers were detected at an early
      (72%) compared to late-stage (46%). Our data support the effectiveness of the screening
      protocol at the University of Kentucky, and subsequent treatment in accordance with National
      Comprehensive Cancer Network guidelines.

      The significance of these findings is that our approach has resulted in the detection of both
      early-stage Type 1 and Type 2 ovarian cancers and these cases have had improved survival when
      compared to that of unscreened cases, indicating that the screen-detected cases are
      associated with a potential survival advantage even for aggressive ovarian carcinomas.

      The primary objective of this study is to prospectively evaluate the false positive (FP)
      percentage generated by the ovarian screening algorithm and determine whether serial
      transvaginal ultrasonography can lower the FP percentage as demonstrated in the retrospective
      analysis. The aim of serial ultrasonography is to decrease FP percentage to 0.32% (positive
      predictive value of 24%) without adversely impacting the results for true positives and false
      negatives. on a "per woman screened basis" since this corresponds to a minimally acceptable
      positive predictive value of 24% or higher. This assumes an average of three screening years
      for each new woman entering the program.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Screening
masking: None (Open Label)
measure: False-positive (FP) percentage
time frame: approximately 3 years
description: Measure the false-positive (FP) rate generated by the ovarian screening algorithm.
arm group label: Participants in the Kentucky Ovarian Cancer Screening Program
arm group type: Experimental
description: Participants from the Kentucky Ovarian Cancer Screening Program who choose to participate in this trial will undergo further serial transvaginal ultrasonography (TVS) screening.
intervention type: Procedure
intervention name: Serial Transvaginal Ultrasonography
description: Participants will undergo transvaginal ultrasonography (TVS) to detect ovarian cancer as part of the Kentucky Ovarian Cancer Screening Program. Those with normal findings will repeat the TVS in one year. Those with abnormal results will repeat the screening in 4-6 weeks.
arm group label: Participants in the Kentucky Ovarian Cancer Screening Program
criteria: 
gender: Female
minimum age: 24 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: John R Van Nagell
role: Principal Investigator
affiliation: University of Kentucky
last name: Tina Payne
phone: 859-323-4687
email: tcpayne@uky.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Kentucky
investigator full name: John R van Nagell
investigator title: Professor
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
sharing ipd: No