<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/NCT03233191</url>
  </required_header>
  <id_info>
    <org_study_id>EA1151</org_study_id>
    <secondary_id>NCI-2017-01111</secondary_id>
    <secondary_id>EA1151</secondary_id>
    <secondary_id>EA1151</secondary_id>
    <secondary_id>EA1151</secondary_id>
    <secondary_id>U10CA180820</secondary_id>
    <secondary_id>U10CA180794</secondary_id>
    <nct_id>NCT03233191</nct_id>
  </id_info>
  <brief_title>Digital Tomosynthesis Mammography and Digital Mammography in Screening Patients for Breast Cancer</brief_title>
  <official_title>Tomosynthesis Mammographic Imaging Screening Trial (TMIST)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ECOG-ACRIN Cancer Research Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Canadian Cancer Trials Group (CCTG)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Eastern Cooperative Oncology Group</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This randomized phase III trial studies digital tomosynthesis mammography and digital&#xD;
      mammography in screening patients for breast cancer. Screening for breast cancer with&#xD;
      tomosynthesis mammography may be superior to digital mammography for breast cancer screening&#xD;
      and may help reduce the need for additional imaging or treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To compare the proportions of participants in the tomosynthesis mammography (TM) and&#xD;
      digital mammography (DM) study arms experiencing the occurrence of an ?advanced? breast&#xD;
      cancer at any time during a period of 4.5 years from randomization, including the period of&#xD;
      active screening and a period of clinical follow-up after the last screen (T4).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To assess the potential effect of age, menopausal and hormonal status, breast density, and&#xD;
      family cancer history on the primary endpoint difference between the two arms.&#xD;
&#xD;
      II. To compare the diagnostic performance of TM and DM, as measured by the area under the&#xD;
      receiver operating characteristic (ROC) curve (AUC), sensitivity, specificity, positive&#xD;
      predictive value (PPV) and negative predictive value (NPV).&#xD;
&#xD;
      III. To compare the recall rates and biopsy rates for TM versus DM, with subset analyses by&#xD;
      the same variables as listed in aim II.&#xD;
&#xD;
      IV. To compare the rate of interval cancers for TM and DM and to assess the mechanism of&#xD;
      diagnosis for these interval cancers with categorization by symptomatic versus (vs)&#xD;
      asymptomatic, and how detected: diagnosed via physical examination, mammography, ultrasound&#xD;
      (US), magnetic resonance imaging (MRI) or other technologies.&#xD;
&#xD;
      V. To examine the correlation between Breast Imaging Reporting and Data System (BIRADS)&#xD;
      imaging features and histologic and genetic features, such as invasive ductal and invasive&#xD;
      lobular histology, high grade, high stage at diagnosis, and aggressive genetic subtypes.&#xD;
&#xD;
      VI. To assess different combinations of TM and synthesized 2 dimensional (2D) or DM in reader&#xD;
      studies to assist in determining the optimum balance between diagnostic performance,&#xD;
      radiation exposure and technique.&#xD;
&#xD;
      VII. To estimate and compare breast-cancer-specific mortality between the two study arms.&#xD;
&#xD;
      VIII. To estimate and compare the prevalence of breast cancer subtypes (luminal A, luminal B,&#xD;
      HER2+, basal-like) low, medium or high proliferation via PAM50 proliferation signatures, and&#xD;
      p53 mutant-like or wild-type-like according to a validated p53 dependent signature in the two&#xD;
      arms, overall and stratified on whether cancers were detected through screening or as&#xD;
      interval cancers, and whether cancers were invasive or in situ.&#xD;
&#xD;
      IX. To classify histologically malignant (true positive cases) and benign lesions (false&#xD;
      positive cases) as normal-like or tumor-like using the PAM50 gene expression assay subtype&#xD;
      (luminal A, luminal B, HER2, basal-like,), and low, medium, or high proliferation according&#xD;
      to PAM50 proliferation signatures, and p53 mutant-like or wild-type-like according to a&#xD;
      validated p53-dependent signature.&#xD;
&#xD;
      X. To assess the agreement between local and expert study pathologists for all breast lesions&#xD;
      (benign and malignant) biopsied during the 4.5 years of screening with TM or DM.&#xD;
&#xD;
      XI. To create a blood and buccal cell biobank for future biomarker and genetic testing.&#xD;
&#xD;
      XII. To compare health care utilization (including cancer care received) and cost of an&#xD;
      episode of breast cancer screening by TM versus DM, overall and within subsets.&#xD;
&#xD;
      XIII. To implement a centralized quality control (QC) monitoring program for both 2D digital&#xD;
      mammography (DM) and tomosynthesis (TM), which provides rapid feedback on image quality,&#xD;
      using quantitative tools, taking advantage of the automated analysis of digital images.&#xD;
&#xD;
      XIV. To assess temporal and site-to site variations in image quality, breast radiation dose,&#xD;
      and other quality control parameters in TM vs. DM.&#xD;
&#xD;
      XV. To refine and implement task-based measures of image quality to assess the effects of&#xD;
      technical parameters, including machine type, and detector spatial and contrast resolution on&#xD;
      measures of diagnostic accuracy for TM.&#xD;
&#xD;
      XVI. To evaluate which QC tests are useful for determination of image quality and those that&#xD;
      are predictive of device failure, in order to recommend an optimal QC program for TM.&#xD;
&#xD;
      OUTLINE: Patients are randomized to 1 of 2 arms.&#xD;
&#xD;
      ARM A: Patients undergo bilateral screening DM with standard craniocaudal (CC) and&#xD;
      mediolateral oblique (MLO) views at baseline, 12, 24, 36, and 48 months if pre-menopausal or&#xD;
      at baseline, 24, and 48 months if post-menopausal.&#xD;
&#xD;
      ARM B: Patients undergo manufacturer-defined screening TM at baseline, 12, 24, 36, and 48&#xD;
      months if pre-menopausal or at baseline, 24, and 48 months if post-menopausal.&#xD;
&#xD;
      After completion of study, patients are followed up for at least 3- 8 years after study&#xD;
      entry.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 28, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2030</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2030</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Participants will be randomized to either Digital Breast Tomography (TM) or Full Field Digital Mammography (DM)</intervention_model_description>
    <primary_purpose>Screening</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of women diagnosed with an advanced breast cancer at any time during a period of 4.5 years from randomization, including the period of active screening and a period of follow up after the last screen</measure>
    <time_frame>4.5 years after last registration</time_frame>
    <description>The cumulative proportions of participants experiencing the primary endpoint in the two study arms will be compared. The primary comparison of the two study arms will be approached from an Intent-to-Treat perspective and will be based on a two-sided test for comparing binomial proportions.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Agreement between local and expert study pathologists for all breast lesions (benign and malignant) biopsied during the five years of screening</measure>
    <time_frame>Up to 8 years</time_frame>
    <description>Measures of agreement such as kappa statistics and concordance coefficients to assess the agreement of local and central pathology readings. In addition, the variability among local pathologists will be examined with respect to the degree of agreement with the central study interpretation. This analysis will utilize mixed models with random effects for local pathologists. There will be up to two central study independent pathologist interpretations for each representative diagnostic slide set.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Breast Imaging-Reporting and Data System (BIRADS) imaging features</measure>
    <time_frame>Up to 8 years</time_frame>
    <description>The correlation between BIRADS imaging features and histologic and genetic features, such as invasive ductal and invasive lobular histology, high grade, high stage at diagnosis, and aggressive genetic subtypes will be examined. Using data on patients with cancer, estimates of the correlation between the two sets of features (BIRADS imaging features and histologic/genetic features) will be derived. Cluster analysis will be used to identify clusters of patients based on imaging features and will examine the association of these clusters with histology and genetic features. Using data from the fu</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Breast-cancer-specific mortality</measure>
    <time_frame>Up to 8 years</time_frame>
    <description>Breast-cancer-specific mortality between the two study arms will be estimated and compared. Information on cancer recurrence and mortality will be obtained for a period of at least 4.5-8 years on all study participants. Mortality rates will be estimated as the ratio of the number of breast cancer deaths during a time period to the number of person-years at risk. Person-years will be measured as time from randomization to breast cancer death or censoring. Cumulative mortality rates from breast cancer at the end of the study period in each arm will be compared via the relative risk (rate ratio).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Centralized quality control (QC) monitoring program implementation</measure>
    <time_frame>Up to 8 years</time_frame>
    <description>Centralized QC monitoring program for both DM and TM, which provides rapid feedback on image quality, using quantitative tools, taking advantage of the automated analysis of digital images. The QC program will provide an auditable trail of QC activities and image quality parameters, while at the same time reducing QC effort required by the technologist at the site.&#xD;
Constant monitoring of data from all sites will occur, and Root Cause Analysis will be performed for non-compliant items. The remote monitoring system will be evaluated in terms of its percent ?up-time?, technologist compliance (vi</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diagnostic and predictive performance of tomosynthesis mammography (TM) and digital mammography (DM) [AUC]</measure>
    <time_frame>Up to 8 years</time_frame>
    <description>ROC analysis will be performed to compare the performance characteristics of DM vs TM at each screening visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess the predictive performance of tomosynthesis mammography (TM) and digital mammography (DM)</measure>
    <time_frame>Up to 8 years</time_frame>
    <description>Compare the predictive characteristics (PPV,NPV,Sens, and Spec) of DM vs TM at each screening visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health care costs (including diagnostic procedures and cancer care received) as the result of an episode of breast cancer screening by tomosynthesis mammography (TM) versus digital mammography (DM)</measure>
    <time_frame>Up to 8 years</time_frame>
    <description>Rates of utilization of key diagnostic procedures (e.g. extra TM or DM views, Ultrasound, Short-term interval follow-up, surgical consultation, percutaneous biopsy with, needle-localized open surgical biopsy, breast MRI) will be estimated; Medicare reimbursement costs will be used to derive a standardized measure of cost per participant; and these costs will be compared across the two study arms. These measures of cost will be compared across study arms using non-parametric methods.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health care utilization (including cancer care received) of an episode of breast cancer screening by tomosynthesis mammography (TM) versus digital mammography (DM)</measure>
    <time_frame>Up to 8 years</time_frame>
    <description>Rates of utilization of key diagnostic procedures (e.g. extra TM or DM views, Ultrasound, Short-term interval follow-up, surgical consultation, percutaneous biopsy with, needle-localized open surgical biopsy, breast MRI) will be estimated and compared across the two study arms. The comparisons will be made using regression modeling</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Histologically malignant (true positive cases) and benign lesions (false positive cases)</measure>
    <time_frame>Up to 8 years</time_frame>
    <description>Classification of histologically benign-appearing lesions (false positive cases) will be explored as normal-like or tumor-like using the PAM50 gene expression assay subtype and low, medium, or high proliferation according to a PAM50 proliferation signature, and p53 mutant-like or wild-type-like according to a validated p53-dependent signature, and according to histological features. The benign-appearing (false positive) biopsies will be characterized using digital histologic analysis tools that capture percent of area represented by stroma, epithelium, and fat as well as the density of nuclei</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevalence of breast cancer subtypes (luminal A, luminal B, HER2+, basal-like) and p53 signature in the two arms</measure>
    <time_frame>Up to 8 years</time_frame>
    <description>Prevalence of breast cancer subtypes (luminal A, luminal B, HER2+, basal-like) and p53 signature in the two arms will be estimated and compared, overall and stratified on whether cancers were detected through screening or as interval cancers. subtypes in each arm and to compare them across arms. The analysis will be performed overall, and stratified by screen detected or interval detected. Estimates of the prevalence of subtypes and confidence intervals will be developed for each screening round and for the full period of screening. The comparison of rates across arms will be based on multinom</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of women diagnosed with an ?advanced? breast cancer in the two arms</measure>
    <time_frame>Up to 8 years</time_frame>
    <description>The potential effect of age, menopausal and hormonal status, breast density, and family cancer history will be assessed on the primary endpoint difference between the two arms. Regression modeling will be used to assess the effect of age, menopausal and hormonal status, breast density, and family cancer history. Multiple imputation will be used to handle missing data in the response and the covariates, and a sensitivity analysis to assumptions about the missing data will be performed. An exploratory analysis using alternative definitions of the primary endpoint will also be conducted in order</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality control (QC) tests useful for determination of image quality and those that are predictive of device failure</measure>
    <time_frame>Up to 8 years</time_frame>
    <description>QC tests that are useful for determination of image quality and those that are predictive of device failure will be evaluated, in order to recommend an optimal QC program for TM. Tests that are most sensitive to changes in system performance will be established and tests that are inferior and/or redundant and can be eliminated. Changes will be tracked against site records of alterations or repairs to the system, recalibration and changes in imaging parameters. Changes in test results will be observed and if they are suggestive that remedial action is required, we will determine after such acti</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of interval cancers</measure>
    <time_frame>Up to 8 years</time_frame>
    <description>The rate of interval cancers for TM and DM will be compared and the mechanism of diagnosis for these interval cancers will be assessed with categorization by symptomatic vs asymptomatic, and how detected: diagnosed via physical examination, mammography, ultrasound (US), magnetic resonance imaging (MRI) or other technologies. Interval cancers are those that occur between screening examinations. Interval cancer rates for each screening occasion and over the full set of screens will be estimated using Wilson intervals and compared across arms using two-sided tests for binomial proportions. The di</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recall rates</measure>
    <time_frame>Up to 8 years</time_frame>
    <description>The recall rates for TM versus (vs) DM will be compared. Recall rates are defined as the number of screening examinations that are interpreted as BIRADS 0, 3, 4 and 5 divided by the total number of screening examinations. Recall rates for each screening occasion and over the full set of screens will be estimated using Wilson intervals and compared across arms using two-sided tests for binomial proportions. Logistic regression will be used to analyze potential differences across patient subsets.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biopsy rates</measure>
    <time_frame>Up to 8 years</time_frame>
    <description>The biopsy rates for TM versus (vs) DM will be compared. biopsy rates are defined as the number of biopsies divided by the total number of screening examinations. rates for each screening occasion and over the full set of screens will be estimated using Wilson intervals and compared across arms using two-sided tests for binomial proportions. Logistic regression will be used to analyze potential differences across patient subsets</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Task-based measure of image quality</measure>
    <time_frame>Up to 8 years</time_frame>
    <description>Task-based measures of image quality will be refined and implemented to assess the effects of technical parameters, including machine type, and detector spatial and contrast resolution on diagnostic accuracy for TM. the diagnostic accuracy of the resulting Task-based analysis, using mathematical observers, will be assessed from image information using techniques based on signal and noise transfer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Variability of quality control parameters</measure>
    <time_frame>Up to 8 years</time_frame>
    <description>The variability of standard quality control parameters will be assessed and compared temporally, within, and across sites for both DM and TM.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">128905</enrollment>
  <condition>Breast Screening</condition>
  <arm_group>
    <arm_group_label>Arm A (digital mammography)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients undergo bilateral screening DM with standard CC and MLO views at baseline, 12, 24, 36, and 48 months if pre-menopausal or at baseline, 24, and 48 months if post-menopausal.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B (digital tomosynthesis mammography)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients undergo manufacturer-defined screening TM at baseline, 12, 24, 36, and 48 months if pre-menopausal or at baseline, 24, and 48 months if post-menopausal.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Digital Mammography</intervention_name>
    <description>Undergo DM</description>
    <arm_group_label>Arm A (digital mammography)</arm_group_label>
    <other_name>Full Field Digital Mammography</other_name>
    <other_name>FFDM</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Digital Tomosynthesis Mammography</intervention_name>
    <description>Undergo TM</description>
    <arm_group_label>Arm B (digital tomosynthesis mammography)</arm_group_label>
    <other_name>DBT</other_name>
    <other_name>Digital Breast Tomosynthesis</other_name>
    <other_name>Digital Tomosynthesis of the Breast</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Arm A (digital mammography)</arm_group_label>
    <arm_group_label>Arm B (digital tomosynthesis mammography)</arm_group_label>
    <other_name>Biomarker analysis</other_name>
    <other_name>genetic analysis</other_name>
    <other_name>PAM50</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women of childbearing potential must not be known to be pregnant or lactating&#xD;
&#xD;
          -  Patients must be scheduled for, or have intent to schedule, a screening mammogram&#xD;
&#xD;
          -  Patients must be able to tolerate digital breast tomosynthesis and full-field digital&#xD;
             mammographic imaging required by protocol.&#xD;
&#xD;
          -  Patients must be willing and able to provide a written informed consent&#xD;
&#xD;
          -  Patients must not have symptoms or signs of benign or malignant breast disease (eg,&#xD;
             nipple discharge, breast lump) warranting a diagnostic rather than a screening&#xD;
             mammogram, and/or other imaging studies (eg, sonogram); patients with breast pain are&#xD;
             eligible as long as other criteria are met&#xD;
&#xD;
          -  Patients must not have had a screening mammogram within the last 11 months prior to&#xD;
             date of randomization&#xD;
&#xD;
          -  Patients must not have previous personal history of breast cancer including ductal&#xD;
             carcinoma in situ&#xD;
&#xD;
          -  Patients must not have breast enhancements (e.g., implants or injections)&#xD;
&#xD;
          -  ANNUAL SCREENING REGIMEN ELIGIBILITY CHECK&#xD;
&#xD;
          -  To be eligible for inclusion in the annual screening regimen one of the following&#xD;
             three conditions must be met in addition to the eligibility criteria above:&#xD;
&#xD;
               -  Patients are pre-menopausal; OR&#xD;
&#xD;
               -  Post-menopausal aged 45-69 with any of the following three risks factors:&#xD;
&#xD;
                    -  Dense breasts (BIRADS density categories c-heterogeneously dense or&#xD;
                       d-extremely dense), or&#xD;
&#xD;
                    -  Family history of breast cancer (first degree relative with breast cancer),&#xD;
                       or, positive genetic testing for any deleterious genes that indicate an&#xD;
                       increased risk for breast cancer, or&#xD;
&#xD;
                    -  Currently on hormone therapy; OR&#xD;
&#xD;
               -  Post-menopausal ages 70-74 with either of the following two risk factors:&#xD;
&#xD;
                    -  Dense breasts (BIRADS density categories c-heterogeneously dense or&#xD;
                       d-extremely dense), or&#xD;
&#xD;
                    -  Currently on hormone therapy&#xD;
&#xD;
          -  Postmenopausal women are defined as those with their last menstrual period more than&#xD;
             12 months prior to study entry; for the purpose of defining menopausal status for&#xD;
             women who have had surgical cessation of their periods, women who no longer have&#xD;
             menses due to hysterectomy and oophorectomy will be considered postmenopausal; women&#xD;
             who no longer have menses due to hysterectomy without oophorectomy will be considered&#xD;
             premenopausal until age 52 and postmenopausal thereafter&#xD;
&#xD;
          -  All other postmenopausal women are eligible for inclusion in the biennial screening&#xD;
             regimen&#xD;
&#xD;
          -  For those women who cannot be assigned to annual or biennial screening at the time of&#xD;
             study entry and randomization because they are postmenopausal, have no family history&#xD;
             or known deleterious breast cancer mutation, are not on hormone therapy AND have not&#xD;
             had a prior mammogram, breast density will be determined by the radiologist?s&#xD;
             recording of it at the time of interpretation of the first study screening&#xD;
             examination, either DM or TM; for those who are randomized to TM, radiologists will&#xD;
             assign BI-RADS density through review of the DM or synthetic DM portion of the TM&#xD;
             examination; such women cannot be part of the planned stratification by screening&#xD;
             frequency and are expected to represent far less than 1% of the Tomosynthesis&#xD;
             Mammographic Imaging Screening Trial (TMIST) population&#xD;
&#xD;
          -  Breast density will be determined by prior mammography reports, when available; all&#xD;
             other risk factors used to determine patient eligibility for annual or biennial&#xD;
             screening will be determined by subject self-report&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>74 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Etta Pisano</last_name>
    <role>Principal Investigator</role>
    <affiliation>ECOG-ACRIN Cancer Research Group</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama at Birmingham Cancer Center</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35233</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>205-934-0220</phone>
      <email>tmyrick@uab.edu</email>
    </contact>
    <investigator>
      <last_name>Stefanie A. Woodard</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Mobile Infirmary Medical Center</name>
      <address>
        <city>Mobile</city>
        <state>Alabama</state>
        <zip>36607</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>251-435-3942</phone>
    </contact>
    <investigator>
      <last_name>Travis Harris</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Banner-University Medical Center Phoenix</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85006</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <email>BannerResearch@bannerhealth.com</email>
    </contact>
    <investigator>
      <last_name>Michael F. Morris</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Arizona College of Medicine Phoenix</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85006</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Suspended</status>
  </location>
  <location>
    <facility>
      <name>Valleywise Comprehensive Health Center - Phoenix</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85008</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>602-344-5775</phone>
    </contact>
    <investigator>
      <last_name>Christina Ferraro</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Hospital in Arizona</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85054</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>855-776-0015</phone>
    </contact>
    <investigator>
      <last_name>Katie N. Hunt</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Scottsdale Medical Imaging Limited</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85258</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>480-425-4170</phone>
      <email>investigator@esmil.com</email>
    </contact>
    <investigator>
      <last_name>Sarah Palestrant</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Arkansas for Medical Sciences</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72205</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>501-686-8274</phone>
    </contact>
    <investigator>
      <last_name>Gwendolyn M. Bryant-Smith</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Kern Radiology Medical Group Inc</name>
      <address>
        <city>Bakersfield</city>
        <state>California</state>
        <zip>93306</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Suspended</status>
  </location>
  <location>
    <facility>
      <name>Los Angeles County-USC Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>323-865-0451</phone>
    </contact>
    <investigator>
      <last_name>Linda H. Larsen</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>USC / Norris Comprehensive Cancer Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>323-865-0451</phone>
    </contact>
    <investigator>
      <last_name>Linda H. Larsen</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Zuckerberg San Francisco General Hospital</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94110</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>415-476-4082</phone>
      <email>Paul.Couey@ucsf.edu</email>
    </contact>
    <investigator>
      <last_name>Rita I. Freimanis</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Colorado Hospital</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>720-848-0650</phone>
    </contact>
    <investigator>
      <last_name>Dulcy E. Wolverton</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Penrose-Saint Francis Healthcare</name>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <zip>80907</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>719-776-6550</phone>
      <email>ResearchTracking@Centura.Org</email>
    </contact>
    <investigator>
      <last_name>Richard L. Deming</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Women's Imaging Center</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80209</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>303-777-2663</phone>
      <email>info@westernstatesncorp.org</email>
    </contact>
    <investigator>
      <last_name>Nicholas DiBella</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Radiology Imaging Associates</name>
      <address>
        <city>Englewood</city>
        <state>Colorado</state>
        <zip>80112</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Suspended</status>
  </location>
  <location>
    <facility>
      <name>UCHealth Highlands Ranch Hospital</name>
      <address>
        <city>Highlands Ranch</city>
        <state>Colorado</state>
        <zip>80129</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>720-848-0650</phone>
    </contact>
    <investigator>
      <last_name>Dulcy E. Wolverton</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UCHealth Lone Tree Health Center</name>
      <address>
        <city>Lone Tree</city>
        <state>Colorado</state>
        <zip>80124</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Helen F Graham Cancer Center</name>
      <address>
        <city>Newark</city>
        <state>Delaware</state>
        <zip>19713</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>302-623-4450</phone>
      <email>mhayden@christianacare.org</email>
    </contact>
    <investigator>
      <last_name>Gregory A. Masters</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>MedStar Georgetown University Hospital</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>202-444-2223</phone>
    </contact>
    <investigator>
      <last_name>Judy H. Song</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Florida Health Science Center - Jacksonville</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32209</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>888-254-7581</phone>
    </contact>
    <investigator>
      <last_name>Parlyn D. Hatch</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Northside Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>404-303-3355</phone>
      <email>ClinicalTrials@northside.com</email>
    </contact>
    <investigator>
      <last_name>Lynn D. Baxter</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Northeast Georgia Medical Center Braselton</name>
      <address>
        <city>Braselton</city>
        <state>Georgia</state>
        <zip>30517</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>770-219-8800</phone>
      <email>cancerpatient.navigator@nghs.com</email>
    </contact>
    <investigator>
      <last_name>Charles H. Nash</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Lewis Cancer and Research Pavilion at Saint Joseph's/Candler</name>
      <address>
        <city>Savannah</city>
        <state>Georgia</state>
        <zip>31405</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>912-819-5704</phone>
      <email>underberga@sjchs.org</email>
    </contact>
    <investigator>
      <last_name>Howard A. Zaren</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Queen's Medical Center</name>
      <address>
        <city>Honolulu</city>
        <state>Hawaii</state>
        <zip>96813</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>808-545-8548</phone>
    </contact>
    <investigator>
      <last_name>Erin Capps</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Saint Alphonsus Cancer Care Center-Boise</name>
      <address>
        <city>Boise</city>
        <state>Idaho</state>
        <zip>83706</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>734-712-3671</phone>
      <email>stephanie.couch@stjoeshealth.org</email>
    </contact>
    <investigator>
      <last_name>John M. Schallenkamp</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Saint Luke's Cancer Institute - Boise</name>
      <address>
        <city>Boise</city>
        <state>Idaho</state>
        <zip>83712</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>208-381-2774</phone>
      <email>eslinget@slhs.org</email>
    </contact>
    <investigator>
      <last_name>Alison K. Conlin</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>John H Stroger Jr Hospital of Cook County</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>312-864-5204</phone>
    </contact>
    <investigator>
      <last_name>Thomas E. Lad</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Carle on Fairchild</name>
      <address>
        <city>Danville</city>
        <state>Illinois</state>
        <zip>61832</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>800-446-5532</phone>
      <email>Research@carle.com</email>
    </contact>
    <investigator>
      <last_name>Kendrith M. Rowland</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Decatur Memorial Hospital</name>
      <address>
        <city>Decatur</city>
        <state>Illinois</state>
        <zip>62526</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>217-876-4762</phone>
      <email>morganthaler.jodi@mhsil.com</email>
    </contact>
    <investigator>
      <last_name>Bryan A. Faller</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Carle Hoopeston Regional Health Center</name>
      <address>
        <city>Hoopeston</city>
        <state>Illinois</state>
        <zip>60942</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>800-446-5532</phone>
      <email>Research@carle.com</email>
    </contact>
    <investigator>
      <last_name>Kendrith M. Rowland</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Carle Physician Group-Mattoon/Charleston</name>
      <address>
        <city>Mattoon</city>
        <state>Illinois</state>
        <zip>61938</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>800-446-5532</phone>
      <email>Research@carle.com</email>
    </contact>
    <investigator>
      <last_name>Kendrith M. Rowland</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Carle Cancer Center</name>
      <address>
        <city>Urbana</city>
        <state>Illinois</state>
        <zip>61801</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>800-446-5532</phone>
      <email>Research@carle.com</email>
    </contact>
    <investigator>
      <last_name>Kendrith M. Rowland</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Indiana University/Melvin and Bren Simon Cancer Center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>317-278-5632</phone>
      <email>iutrials@iu.edu</email>
    </contact>
    <investigator>
      <last_name>Steven M. Westphal</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Community Hospital</name>
      <address>
        <city>Munster</city>
        <state>Indiana</state>
        <zip>46321</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>219-836-3349</phone>
    </contact>
    <investigator>
      <last_name>Mohamad Kassar</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Women's Diagnostic Center - Munster</name>
      <address>
        <city>Munster</city>
        <state>Indiana</state>
        <zip>46321</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>219-934-8869</phone>
      <email>mnicholson@comhs.org</email>
    </contact>
    <investigator>
      <last_name>Kendrith M. Rowland</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Mercy Medical Center - Des Moines</name>
      <address>
        <city>Des Moines</city>
        <state>Iowa</state>
        <zip>50314</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>515-643-2196</phone>
      <email>cancerresearch@mercydesmoines.org</email>
    </contact>
    <investigator>
      <last_name>Richard L. Deming</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Iowa/Holden Comprehensive Cancer Center</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>800-237-1225</phone>
    </contact>
    <investigator>
      <last_name>Fabiana Policeni</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Owensboro Health Mitchell Memorial Cancer Center</name>
      <address>
        <city>Owensboro</city>
        <state>Kentucky</state>
        <zip>42303</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>270-691-8094</phone>
      <email>vanissa.sorrels@owensborohealth.org</email>
    </contact>
    <investigator>
      <last_name>Patrick G. Padgett</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Mary Bird Perkins Cancer Center</name>
      <address>
        <city>Baton Rouge</city>
        <state>Louisiana</state>
        <zip>70809</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Woman's Hospital</name>
      <address>
        <city>Baton Rouge</city>
        <state>Louisiana</state>
        <zip>70817</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>225-215-1353</phone>
      <email>Clinicalreserach@marybird.com</email>
    </contact>
    <investigator>
      <last_name>James F. Ruiz</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Tulane University Health Sciences Center</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70112</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>504-988-6121</phone>
    </contact>
    <investigator>
      <last_name>Kendra M. Harris</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University Medical Center New Orleans</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70112</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>504-210-3539</phone>
      <email>emede1@lsuhsc.edu</email>
    </contact>
    <investigator>
      <last_name>Mignonne B. Morrell</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ochsner LSU Health Saint Mary's Medical Center</name>
      <address>
        <city>Shreveport</city>
        <state>Louisiana</state>
        <zip>71101</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>318-813-1404</phone>
      <email>LPost@lsuhsc.edu</email>
    </contact>
    <investigator>
      <last_name>Jerry McLarty</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>LSU Health Sciences Center at Shreveport</name>
      <address>
        <city>Shreveport</city>
        <state>Louisiana</state>
        <zip>71103</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>318-813-1404</phone>
      <email>LPost@lsuhsc.edu</email>
    </contact>
    <investigator>
      <last_name>Jerry McLarty</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente - Kensington Medical Center</name>
      <address>
        <city>Kensington</city>
        <state>Maryland</state>
        <zip>20895</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>301-816-7218</phone>
    </contact>
    <investigator>
      <last_name>Ainsley V. MacLean</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Boston Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02118</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>617-638-8265</phone>
    </contact>
    <investigator>
      <last_name>Michael D. Fishman</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UMass Memorial Medical Center - University Campus</name>
      <address>
        <city>Worcester</city>
        <state>Massachusetts</state>
        <zip>01655</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>508-856-3216</phone>
      <email>cancer.research@umassmed.edu</email>
    </contact>
    <investigator>
      <last_name>Gopal Vijayaraghavan</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Saint Joseph Mercy Hospital</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48106</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>734-712-3671</phone>
      <email>stephanie.couch@stjoeshealth.org</email>
    </contact>
    <investigator>
      <last_name>Philip J. Stella</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Michigan Comprehensive Cancer Center</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>800-865-1125</phone>
    </contact>
    <investigator>
      <last_name>Stephanie Patterson</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Bronson Battle Creek</name>
      <address>
        <city>Battle Creek</city>
        <state>Michigan</state>
        <zip>49017</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>616-391-1230</phone>
      <email>crcwm-regulatory@crcwm.org</email>
    </contact>
    <investigator>
      <last_name>Kathleen J. Yost</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Wayne State University/Karmanos Cancer Institute</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>313-576-9790</phone>
      <email>ctoadmin@karmanos.org</email>
    </contact>
    <investigator>
      <last_name>Alit J. Yousif</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Henry Ford Hospital</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>313-916-3721</phone>
      <email>CTOResearch@hfhs.org</email>
    </contact>
    <investigator>
      <last_name>Ding Wang</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Weisberg Cancer Treatment Center</name>
      <address>
        <city>Farmington Hills</city>
        <state>Michigan</state>
        <zip>48334</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>313-576-9790</phone>
      <email>ctoadmin@karmanos.org</email>
    </contact>
    <investigator>
      <last_name>Alit J. Yousif</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Spectrum Health at Butterworth Campus</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49503</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>616-391-1230</phone>
      <email>crcwm-regulatory@crcwm.org</email>
    </contact>
    <investigator>
      <last_name>Kathleen J. Yost</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>West Michigan Cancer Center</name>
      <address>
        <city>Kalamazoo</city>
        <state>Michigan</state>
        <zip>49007</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>616-391-1230</phone>
      <email>crcwm-regulatory@crcwm.org</email>
    </contact>
    <investigator>
      <last_name>Kathleen J. Yost</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Henry Ford West Bloomfield Hospital</name>
      <address>
        <city>West Bloomfield</city>
        <state>Michigan</state>
        <zip>48322</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>313-916-3721</phone>
      <email>CTOResearch@hfhs.org</email>
    </contact>
    <investigator>
      <last_name>Ding Wang</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Essentia Health Cancer Center</name>
      <address>
        <city>Duluth</city>
        <state>Minnesota</state>
        <zip>55805</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>218-786-3308</phone>
      <email>CancerTrials@EssentiaHealth.org</email>
    </contact>
    <investigator>
      <last_name>Bret E. Friday</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hennepin County Medical Center</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55415</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>952-993-1517</phone>
      <email>mmcorc@healthpartners.com</email>
    </contact>
    <investigator>
      <last_name>David M. King</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic in Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>855-776-0015</phone>
    </contact>
    <investigator>
      <last_name>Katie N. Hunt</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Park Nicollet Clinic - Saint Louis Park</name>
      <address>
        <city>Saint Louis Park</city>
        <state>Minnesota</state>
        <zip>55416</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>952-993-1517</phone>
      <email>mmcorc@healthpartners.com</email>
    </contact>
    <investigator>
      <last_name>David M. King</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Regions Hospital</name>
      <address>
        <city>Saint Paul</city>
        <state>Minnesota</state>
        <zip>55101</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>952-993-1517</phone>
      <email>mmcorc@healthpartners.com</email>
    </contact>
    <investigator>
      <last_name>David M. King</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sanford Thief River Falls Medical Center</name>
      <address>
        <city>Thief River Falls</city>
        <state>Minnesota</state>
        <zip>56701</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>605-312-3320</phone>
    </contact>
    <investigator>
      <last_name>Preston D. Steen</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Essentia Health Virginia Clinic</name>
      <address>
        <city>Virginia</city>
        <state>Minnesota</state>
        <zip>55792</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>218-786-3308</phone>
      <email>CancerTrials@EssentiaHealth.org</email>
    </contact>
    <investigator>
      <last_name>Bret E. Friday</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Carson Tahoe Regional Medical Center</name>
      <address>
        <city>Carson City</city>
        <state>Nevada</state>
        <zip>89703</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>702-384-0013</phone>
      <email>research@sncrf.org</email>
    </contact>
    <investigator>
      <last_name>John A. Ellerton</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hunterdon Medical Center</name>
      <address>
        <city>Flemington</city>
        <state>New Jersey</state>
        <zip>08822</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>908-237-2330</phone>
    </contact>
    <investigator>
      <last_name>Kenneth B. Blankstein</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Saint Peter's University Hospital</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08901</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>732-745-8600</phone>
      <phone_ext>6163</phone_ext>
      <email>kcovert@saintpetersuh.com</email>
    </contact>
    <investigator>
      <last_name>Susan A. McManus</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Riverview Medical Center/Booker Cancer Center</name>
      <address>
        <city>Red Bank</city>
        <state>New Jersey</state>
        <zip>07701</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>732-530-2382</phone>
    </contact>
    <investigator>
      <last_name>Bokran Won</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sidney Kimmel Cancer Center Washington Township</name>
      <address>
        <city>Sewell</city>
        <state>New Jersey</state>
        <zip>08080</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>215-600-9151</phone>
      <email>ONCTrialNow@jefferson.edu</email>
    </contact>
    <investigator>
      <last_name>Jason Shames</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of New Mexico Cancer Center</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87102</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>505-925-0366</phone>
      <email>LByatt@nmcca.org</email>
    </contact>
    <investigator>
      <last_name>Ursa A. Brown-Glaberman</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Montefiore Medical Center-Einstein Campus</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10461</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>718-379-6866</phone>
      <email>eskwak@montefiore.org</email>
    </contact>
    <investigator>
      <last_name>Della F. Makower</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Montefiore Medical Center-Weiler Hospital</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10461</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Suspended</status>
  </location>
  <location>
    <facility>
      <name>Arnot Ogden Medical Center/Falck Cancer Center</name>
      <address>
        <city>Elmira</city>
        <state>New York</state>
        <zip>14905</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>607-271-7000</phone>
    </contact>
    <investigator>
      <last_name>Chi K. Tsang</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>212-305-6361</phone>
      <email>nr2616@cumc.columbia.edu</email>
    </contact>
    <investigator>
      <last_name>Allison Borowski</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>NYP/Weill Cornell Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>212-746-1848</phone>
    </contact>
    <investigator>
      <last_name>Michele B. Drotman</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Rochester</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>585-275-5830</phone>
    </contact>
    <investigator>
      <last_name>Paul M. Barr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UNC Lineberger Comprehensive Cancer Center</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>877-668-0683</phone>
      <email>cancerclinicaltrials@med.unc.edu</email>
    </contact>
    <investigator>
      <last_name>Cherie Kuzmiak</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>888-275-3853</phone>
    </contact>
    <investigator>
      <last_name>Lars J. Grimm</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of North Carolina-Hillsborough Campus</name>
      <address>
        <city>Hillsborough</city>
        <state>North Carolina</state>
        <zip>27278</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>877-668-0683</phone>
      <email>cancerclinicaltrials@med.unc.edu</email>
    </contact>
    <investigator>
      <last_name>Cherie Kuzmiak</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Wake Forest University Health Sciences</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>336-713-6771</phone>
    </contact>
    <investigator>
      <last_name>Kelly Brozzetti Cronin</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sanford Bismarck Medical Center</name>
      <address>
        <city>Bismarck</city>
        <state>North Dakota</state>
        <zip>58501</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>701-323-5760</phone>
      <email>OncologyClinicalTrialsFargo@sanfordhealth.org</email>
    </contact>
    <investigator>
      <last_name>Preston D. Steen</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Southpointe-Sanford Medical Center Fargo</name>
      <address>
        <city>Fargo</city>
        <state>North Dakota</state>
        <zip>58103</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>605-312-3320</phone>
    </contact>
    <investigator>
      <last_name>Preston D. Steen</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Aultman Health Foundation</name>
      <address>
        <city>Canton</city>
        <state>Ohio</state>
        <zip>44710</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>330-363-7274</phone>
      <email>ClinicalReserachDept@aultman.com</email>
    </contact>
    <investigator>
      <last_name>Shruti Trehan</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati Cancer Center-UC Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45219</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>513-584-7698</phone>
      <email>cancer@uchealth.com</email>
    </contact>
    <investigator>
      <last_name>Lawrence D. Sobel</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Foundation</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>866-223-8100</phone>
      <email>TaussigResearch@ccf.org</email>
    </contact>
    <investigator>
      <last_name>Alice Rim</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ohio State University Comprehensive Cancer Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>800-293-5066</phone>
      <email>Jamesline@osumc.edu</email>
    </contact>
    <investigator>
      <last_name>Jeffrey R. Hawley</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Easton Hospital</name>
      <address>
        <city>Easton</city>
        <state>Pennsylvania</state>
        <zip>18042</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Suspended</status>
  </location>
  <location>
    <facility>
      <name>Penn State Milton S Hershey Medical Center</name>
      <address>
        <city>Hershey</city>
        <state>Pennsylvania</state>
        <zip>17033-0850</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>717-531-3779</phone>
      <email>CTO@hmc.psu.edu</email>
    </contact>
    <investigator>
      <last_name>Rebecca T. Sivarajah</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Pennsylvania Hospital</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>800-789-7366</phone>
    </contact>
    <investigator>
      <last_name>Brian S. Englander</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Thomas Jefferson University Hospital</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>215-600-9151</phone>
      <email>ONCTrialNow@jefferson.edu</email>
    </contact>
    <investigator>
      <last_name>Jason Shames</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Fox Chase Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19111</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>215-728-4790</phone>
    </contact>
    <investigator>
      <last_name>Meghan Boros</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Allegheny General Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15212</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>877-284-2000</phone>
    </contact>
    <investigator>
      <last_name>Zidnia M. Conde-Colon</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Wexford Health and Wellness Pavilion</name>
      <address>
        <city>Wexford</city>
        <state>Pennsylvania</state>
        <zip>15090</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>412-359-3043</phone>
      <email>ddefazio@wpahs.org</email>
    </contact>
    <investigator>
      <last_name>Zidnia M. Conde-Colon</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>843-792-9321</phone>
      <email>hcc-clinical-trials@musc.edu</email>
    </contact>
    <investigator>
      <last_name>Dag Pavic</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Prisma Health Richland Hospital</name>
      <address>
        <city>Columbia</city>
        <state>South Carolina</state>
        <zip>29203</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>864-241-6251</phone>
    </contact>
    <investigator>
      <last_name>Ki Y. Chung</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Prisma Health Greenville Memorial Hospital</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29605</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>864-241-6251</phone>
    </contact>
    <investigator>
      <last_name>Ki Y. Chung</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>MUSC Health East Cooper</name>
      <address>
        <city>Mount Pleasant</city>
        <state>South Carolina</state>
        <zip>29464</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>843-792-9321</phone>
      <email>hcc-clinical-trials@musc.edu</email>
    </contact>
    <investigator>
      <last_name>Dag Pavic</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Spartanburg Medical Center</name>
      <address>
        <city>Spartanburg</city>
        <state>South Carolina</state>
        <zip>29303</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>864-560-6104</phone>
      <email>kmertz-rivera@gibbscc.org</email>
    </contact>
    <investigator>
      <last_name>Amarinthia (Amy) Curtis</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Spartanburg Medical Center - Mary Black Campus</name>
      <address>
        <city>Spartanburg</city>
        <state>South Carolina</state>
        <zip>29307</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>864-560-6812</phone>
    </contact>
    <investigator>
      <last_name>Amarinthia (Amy) Curtis</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Tennessee - Knoxville</name>
      <address>
        <city>Knoxville</city>
        <state>Tennessee</state>
        <zip>37920</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>865-544-9773</phone>
    </contact>
    <investigator>
      <last_name>Garnetta I. Morin-Ducote</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Baptist Memorial Hospital and Cancer Center-Memphis</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38120</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Suspended</status>
  </location>
  <location>
    <facility>
      <name>Baptist Memorial Hospital for Women</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38120</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>901-226-1366</phone>
      <email>BCCclintrials@bmhcc.org</email>
    </contact>
    <investigator>
      <last_name>Evelyn W. Gayden</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Vanderbilt Breast Center at One Hundred Oaks</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37204</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>800-811-8480</phone>
    </contact>
    <investigator>
      <last_name>Reagan Leverett</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University/Ingram Cancer Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>800-811-8480</phone>
    </contact>
    <investigator>
      <last_name>Reagan Leverett</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UT Southwestern/Simmons Cancer Center-Dallas</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>214-648-7097</phone>
      <email>canceranswerline@UTSouthwestern.edu</email>
    </contact>
    <investigator>
      <last_name>W. P. Evans</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>877-632-6789</phone>
      <email>askmdanderson@mdanderson.org</email>
    </contact>
    <investigator>
      <last_name>Gary J. Whitman</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Memorial Hermann Texas Medical Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>713-792-3245</phone>
    </contact>
    <investigator>
      <last_name>Claudia Cotes</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University Hospital</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>210-358-4176</phone>
      <email>evelyn.swenson-britt@uhs-sa.com</email>
    </contact>
    <investigator>
      <last_name>Pamela M. Otto</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Virginia Cancer Center</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22908</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>434-243-6303</phone>
      <email>uvacancertrials@hscmail.mcc.virginia.edu</email>
    </contact>
    <investigator>
      <last_name>Matthew M. Miller</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sentara Leigh Hospital</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23502</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>757-388-5109</phone>
      <email>djoverto@sentara.com</email>
    </contact>
    <investigator>
      <last_name>John K. Plemmons</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sentara Norfolk General Hospital</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23507</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>757-388-2406</phone>
    </contact>
    <investigator>
      <last_name>John K. Plemmons</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sentara Princess Anne Hospital</name>
      <address>
        <city>Virginia Beach</city>
        <state>Virginia</state>
        <zip>23456</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>757-388-5109</phone>
      <email>djoverto@sentara.com</email>
    </contact>
    <investigator>
      <last_name>John K. Plemmons</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Swedish Medical Center-First Hill</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98122-4307</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>206-215-3086</phone>
      <email>PCRC-NCORP@Swedish.org</email>
    </contact>
    <investigator>
      <last_name>Alison K. Conlin</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>West Virginia University Healthcare</name>
      <address>
        <city>Morgantown</city>
        <state>West Virginia</state>
        <zip>26506</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>304-293-7374</phone>
      <email>cancertrialsinfo@hsc.wvu.edu</email>
    </contact>
    <investigator>
      <last_name>Cimmie L. Shahan</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>ThedaCare Regional Cancer Center</name>
      <address>
        <city>Appleton</city>
        <state>Wisconsin</state>
        <zip>54911</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>920-364-3605</phone>
      <email>ResearchDept@thedacare.org</email>
    </contact>
    <investigator>
      <last_name>Susan Sung</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Gundersen Lutheran Medical Center</name>
      <address>
        <city>La Crosse</city>
        <state>Wisconsin</state>
        <zip>54601</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>608-775-2385</phone>
      <email>cancerctr@gundersenhealth.org</email>
    </contact>
    <investigator>
      <last_name>Andrew D. Prather</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin Hospital and Clinics</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>800-622-8922</phone>
    </contact>
    <investigator>
      <last_name>Mai A. Elezaby</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Marshfield Medical Center-Marshfield</name>
      <address>
        <city>Marshfield</city>
        <state>Wisconsin</state>
        <zip>54449</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>800-782-8581</phone>
      <email>oncology.clinical.trials@marshfieldresearch.org</email>
    </contact>
    <investigator>
      <last_name>Adedayo A. Onitilo</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>ProHealth D N Greenwald Center</name>
      <address>
        <city>Mukwonago</city>
        <state>Wisconsin</state>
        <zip>53149</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <email>research.institute@phci.org</email>
    </contact>
    <investigator>
      <last_name>Timothy R. Wassenaar</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>ProHealth Oconomowoc Memorial Hospital</name>
      <address>
        <city>Oconomowoc</city>
        <state>Wisconsin</state>
        <zip>53066</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>262-928-7878</phone>
    </contact>
    <investigator>
      <last_name>Timothy R. Wassenaar</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UW Cancer Center at ProHealth Care</name>
      <address>
        <city>Waukesha</city>
        <state>Wisconsin</state>
        <zip>53188</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>262-928-5539</phone>
      <email>Chanda.miller@phci.org</email>
    </contact>
    <investigator>
      <last_name>Timothy R. Wassenaar</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CERIM</name>
      <address>
        <city>Buenos Aires</city>
        <zip>1425</zip>
        <country>Argentina</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <email>ecog.rss@jimmy.harvard.edu</email>
    </contact>
    <investigator>
      <last_name>Daniel E. Lehrer</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>BCCA-Vancouver Cancer Centre</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V5Z 4E6</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>888-939-3333</phone>
    </contact>
    <investigator>
      <last_name>Paula B. Gordon</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Saint Joseph's Health Centre</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 4V2</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>888-823-5923</phone>
      <email>ctsucontact@westat.com</email>
    </contact>
    <investigator>
      <last_name>Anat Kornecki</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Ottawa Hospital and Cancer Center-General Campus</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1H 8L6</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>613-761-4395</phone>
    </contact>
    <investigator>
      <last_name>Jean M. Seely</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Odette Cancer Centre- Sunnybrook Health Sciences Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4N 3M5</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>416-480-5000</phone>
    </contact>
    <investigator>
      <last_name>Roberta A. Jong</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Mount Sinai Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1X5</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>416-586-4800</phone>
    </contact>
    <investigator>
      <last_name>Vivianne A. Freitas</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hopital Du Sacre-Coeur de Montreal</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H4J 1C5</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>514-338-2172</phone>
    </contact>
    <investigator>
      <last_name>Caroline Samson</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Quebec-Hopital du Saint-Sacrement (HSS)</name>
      <address>
        <city>Quebec City</city>
        <state>Quebec</state>
        <zip>G1S 4L8</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>418-649-5593</phone>
      <email>jbegin@uresp.ulaval.ca</email>
    </contact>
    <investigator>
      <last_name>Christine Desbiens</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>National Cancer Center-Korea</name>
      <address>
        <city>Goyang-si</city>
        <state>Gyeonggi-do</state>
        <zip>410-769</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>82-31-920-1934</phone>
    </contact>
    <investigator>
      <last_name>Chan Wha Lee</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>San Juan City Hospital</name>
      <address>
        <city>San Juan</city>
        <zip>00936</zip>
        <country>Puerto Rico</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Site Public Contact</last_name>
      <phone>787-763-1296</phone>
    </contact>
    <investigator>
      <last_name>Luis Baez-Diaz</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Canada</country>
    <country>Korea, Republic of</country>
    <country>Puerto Rico</country>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>July 5, 2017</study_first_submitted>
  <study_first_submitted_qc>July 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2017</study_first_posted>
  <last_update_submitted>June 21, 2023</last_update_submitted>
  <last_update_submitted_qc>June 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Digital Mammography</keyword>
  <keyword>Breast Tomography</keyword>
  <keyword>Screening Mammography</keyword>
  <keyword>TMIST</keyword>
  <!-- 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/NCT03233191
org study id: EA1151
secondary id: NCI-2017-01111
secondary id: EA1151
secondary id: EA1151
secondary id: EA1151
secondary id: U10CA180820
secondary id: U10CA180794
nct id: NCT03233191
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This randomized phase III trial studies digital tomosynthesis mammography and digital
      mammography in screening patients for breast cancer. Screening for breast cancer with
      tomosynthesis mammography may be superior to digital mammography for breast cancer screening
      and may help reduce the need for additional imaging or treatment.
PRIMARY OBJECTIVES:

      I. To compare the proportions of participants in the tomosynthesis mammography (TM) and
      digital mammography (DM) study arms experiencing the occurrence of an ?advanced? breast
      cancer at any time during a period of 4.5 years from randomization, including the period of
      active screening and a period of clinical follow-up after the last screen (T4).

      SECONDARY OBJECTIVES:

      I. To assess the potential effect of age, menopausal and hormonal status, breast density, and
      family cancer history on the primary endpoint difference between the two arms.

      II. To compare the diagnostic performance of TM and DM, as measured by the area under the
      receiver operating characteristic (ROC) curve (AUC), sensitivity, specificity, positive
      predictive value (PPV) and negative predictive value (NPV).

      III. To compare the recall rates and biopsy rates for TM versus DM, with subset analyses by
      the same variables as listed in aim II.

      IV. To compare the rate of interval cancers for TM and DM and to assess the mechanism of
      diagnosis for these interval cancers with categorization by symptomatic versus (vs)
      asymptomatic, and how detected: diagnosed via physical examination, mammography, ultrasound
      (US), magnetic resonance imaging (MRI) or other technologies.

      V. To examine the correlation between Breast Imaging Reporting and Data System (BIRADS)
      imaging features and histologic and genetic features, such as invasive ductal and invasive
      lobular histology, high grade, high stage at diagnosis, and aggressive genetic subtypes.

      VI. To assess different combinations of TM and synthesized 2 dimensional (2D) or DM in reader
      studies to assist in determining the optimum balance between diagnostic performance,
      radiation exposure and technique.

      VII. To estimate and compare breast-cancer-specific mortality between the two study arms.

      VIII. To estimate and compare the prevalence of breast cancer subtypes (luminal A, luminal B,
      HER2+, basal-like) low, medium or high proliferation via PAM50 proliferation signatures, and
      p53 mutant-like or wild-type-like according to a validated p53 dependent signature in the two
      arms, overall and stratified on whether cancers were detected through screening or as
      interval cancers, and whether cancers were invasive or in situ.

      IX. To classify histologically malignant (true positive cases) and benign lesions (false
      positive cases) as normal-like or tumor-like using the PAM50 gene expression assay subtype
      (luminal A, luminal B, HER2, basal-like,), and low, medium, or high proliferation according
      to PAM50 proliferation signatures, and p53 mutant-like or wild-type-like according to a
      validated p53-dependent signature.

      X. To assess the agreement between local and expert study pathologists for all breast lesions
      (benign and malignant) biopsied during the 4.5 years of screening with TM or DM.

      XI. To create a blood and buccal cell biobank for future biomarker and genetic testing.

      XII. To compare health care utilization (including cancer care received) and cost of an
      episode of breast cancer screening by TM versus DM, overall and within subsets.

      XIII. To implement a centralized quality control (QC) monitoring program for both 2D digital
      mammography (DM) and tomosynthesis (TM), which provides rapid feedback on image quality,
      using quantitative tools, taking advantage of the automated analysis of digital images.

      XIV. To assess temporal and site-to site variations in image quality, breast radiation dose,
      and other quality control parameters in TM vs. DM.

      XV. To refine and implement task-based measures of image quality to assess the effects of
      technical parameters, including machine type, and detector spatial and contrast resolution on
      measures of diagnostic accuracy for TM.

      XVI. To evaluate which QC tests are useful for determination of image quality and those that
      are predictive of device failure, in order to recommend an optimal QC program for TM.

      OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM A: Patients undergo bilateral screening DM with standard craniocaudal (CC) and
      mediolateral oblique (MLO) views at baseline, 12, 24, 36, and 48 months if pre-menopausal or
      at baseline, 24, and 48 months if post-menopausal.

      ARM B: Patients undergo manufacturer-defined screening TM at baseline, 12, 24, 36, and 48
      months if pre-menopausal or at baseline, 24, and 48 months if post-menopausal.

      After completion of study, patients are followed up for at least 3- 8 years after study
      entry.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participants will be randomized to either Digital Breast Tomography (TM) or Full Field Digital Mammography (DM)
primary purpose: Screening
masking: None (Open Label)
measure: Proportion of women diagnosed with an advanced breast cancer at any time during a period of 4.5 years from randomization, including the period of active screening and a period of follow up after the last screen
time frame: 4.5 years after last registration
description: The cumulative proportions of participants experiencing the primary endpoint in the two study arms will be compared. The primary comparison of the two study arms will be approached from an Intent-to-Treat perspective and will be based on a two-sided test for comparing binomial proportions.
measure: Agreement between local and expert study pathologists for all breast lesions (benign and malignant) biopsied during the five years of screening
time frame: Up to 8 years
description: Measures of agreement such as kappa statistics and concordance coefficients to assess the agreement of local and central pathology readings. In addition, the variability among local pathologists will be examined with respect to the degree of agreement with the central study interpretation. This analysis will utilize mixed models with random effects for local pathologists. There will be up to two central study independent pathologist interpretations for each representative diagnostic slide set.
measure: Breast Imaging-Reporting and Data System (BIRADS) imaging features
time frame: Up to 8 years
description: The correlation between BIRADS imaging features and histologic and genetic features, such as invasive ductal and invasive lobular histology, high grade, high stage at diagnosis, and aggressive genetic subtypes will be examined. Using data on patients with cancer, estimates of the correlation between the two sets of features (BIRADS imaging features and histologic/genetic features) will be derived. Cluster analysis will be used to identify clusters of patients based on imaging features and will examine the association of these clusters with histology and genetic features. Using data from the fu
measure: Breast-cancer-specific mortality
time frame: Up to 8 years
description: Breast-cancer-specific mortality between the two study arms will be estimated and compared. Information on cancer recurrence and mortality will be obtained for a period of at least 4.5-8 years on all study participants. Mortality rates will be estimated as the ratio of the number of breast cancer deaths during a time period to the number of person-years at risk. Person-years will be measured as time from randomization to breast cancer death or censoring. Cumulative mortality rates from breast cancer at the end of the study period in each arm will be compared via the relative risk (rate ratio).
measure: Centralized quality control (QC) monitoring program implementation
time frame: Up to 8 years
description: Centralized QC monitoring program for both DM and TM, which provides rapid feedback on image quality, using quantitative tools, taking advantage of the automated analysis of digital images. The QC program will provide an auditable trail of QC activities and image quality parameters, while at the same time reducing QC effort required by the technologist at the site.
Constant monitoring of data from all sites will occur, and Root Cause Analysis will be performed for non-compliant items. The remote monitoring system will be evaluated in terms of its percent ?up-time?, technologist compliance (vi
measure: Diagnostic and predictive performance of tomosynthesis mammography (TM) and digital mammography (DM) [AUC]
time frame: Up to 8 years
description: ROC analysis will be performed to compare the performance characteristics of DM vs TM at each screening visit
measure: Assess the predictive performance of tomosynthesis mammography (TM) and digital mammography (DM)
time frame: Up to 8 years
description: Compare the predictive characteristics (PPV,NPV,Sens, and Spec) of DM vs TM at each screening visit
measure: Health care costs (including diagnostic procedures and cancer care received) as the result of an episode of breast cancer screening by tomosynthesis mammography (TM) versus digital mammography (DM)
time frame: Up to 8 years
description: Rates of utilization of key diagnostic procedures (e.g. extra TM or DM views, Ultrasound, Short-term interval follow-up, surgical consultation, percutaneous biopsy with, needle-localized open surgical biopsy, breast MRI) will be estimated; Medicare reimbursement costs will be used to derive a standardized measure of cost per participant; and these costs will be compared across the two study arms. These measures of cost will be compared across study arms using non-parametric methods.
measure: Health care utilization (including cancer care received) of an episode of breast cancer screening by tomosynthesis mammography (TM) versus digital mammography (DM)
time frame: Up to 8 years
description: Rates of utilization of key diagnostic procedures (e.g. extra TM or DM views, Ultrasound, Short-term interval follow-up, surgical consultation, percutaneous biopsy with, needle-localized open surgical biopsy, breast MRI) will be estimated and compared across the two study arms. The comparisons will be made using regression modeling
measure: Histologically malignant (true positive cases) and benign lesions (false positive cases)
time frame: Up to 8 years
description: Classification of histologically benign-appearing lesions (false positive cases) will be explored as normal-like or tumor-like using the PAM50 gene expression assay subtype and low, medium, or high proliferation according to a PAM50 proliferation signature, and p53 mutant-like or wild-type-like according to a validated p53-dependent signature, and according to histological features. The benign-appearing (false positive) biopsies will be characterized using digital histologic analysis tools that capture percent of area represented by stroma, epithelium, and fat as well as the density of nuclei
measure: Prevalence of breast cancer subtypes (luminal A, luminal B, HER2+, basal-like) and p53 signature in the two arms
time frame: Up to 8 years
description: Prevalence of breast cancer subtypes (luminal A, luminal B, HER2+, basal-like) and p53 signature in the two arms will be estimated and compared, overall and stratified on whether cancers were detected through screening or as interval cancers. subtypes in each arm and to compare them across arms. The analysis will be performed overall, and stratified by screen detected or interval detected. Estimates of the prevalence of subtypes and confidence intervals will be developed for each screening round and for the full period of screening. The comparison of rates across arms will be based on multinom
measure: Proportion of women diagnosed with an ?advanced? breast cancer in the two arms
time frame: Up to 8 years
description: The potential effect of age, menopausal and hormonal status, breast density, and family cancer history will be assessed on the primary endpoint difference between the two arms. Regression modeling will be used to assess the effect of age, menopausal and hormonal status, breast density, and family cancer history. Multiple imputation will be used to handle missing data in the response and the covariates, and a sensitivity analysis to assumptions about the missing data will be performed. An exploratory analysis using alternative definitions of the primary endpoint will also be conducted in order
measure: Quality control (QC) tests useful for determination of image quality and those that are predictive of device failure
time frame: Up to 8 years
description: QC tests that are useful for determination of image quality and those that are predictive of device failure will be evaluated, in order to recommend an optimal QC program for TM. Tests that are most sensitive to changes in system performance will be established and tests that are inferior and/or redundant and can be eliminated. Changes will be tracked against site records of alterations or repairs to the system, recalibration and changes in imaging parameters. Changes in test results will be observed and if they are suggestive that remedial action is required, we will determine after such acti
measure: Rate of interval cancers
time frame: Up to 8 years
description: The rate of interval cancers for TM and DM will be compared and the mechanism of diagnosis for these interval cancers will be assessed with categorization by symptomatic vs asymptomatic, and how detected: diagnosed via physical examination, mammography, ultrasound (US), magnetic resonance imaging (MRI) or other technologies. Interval cancers are those that occur between screening examinations. Interval cancer rates for each screening occasion and over the full set of screens will be estimated using Wilson intervals and compared across arms using two-sided tests for binomial proportions. The di
measure: Recall rates
time frame: Up to 8 years
description: The recall rates for TM versus (vs) DM will be compared. Recall rates are defined as the number of screening examinations that are interpreted as BIRADS 0, 3, 4 and 5 divided by the total number of screening examinations. Recall rates for each screening occasion and over the full set of screens will be estimated using Wilson intervals and compared across arms using two-sided tests for binomial proportions. Logistic regression will be used to analyze potential differences across patient subsets.
measure: Biopsy rates
time frame: Up to 8 years
description: The biopsy rates for TM versus (vs) DM will be compared. biopsy rates are defined as the number of biopsies divided by the total number of screening examinations. rates for each screening occasion and over the full set of screens will be estimated using Wilson intervals and compared across arms using two-sided tests for binomial proportions. Logistic regression will be used to analyze potential differences across patient subsets
measure: Task-based measure of image quality
time frame: Up to 8 years
description: Task-based measures of image quality will be refined and implemented to assess the effects of technical parameters, including machine type, and detector spatial and contrast resolution on diagnostic accuracy for TM. the diagnostic accuracy of the resulting Task-based analysis, using mathematical observers, will be assessed from image information using techniques based on signal and noise transfer.
measure: Variability of quality control parameters
time frame: Up to 8 years
description: The variability of standard quality control parameters will be assessed and compared temporally, within, and across sites for both DM and TM.
arm group label: Arm A (digital mammography)
arm group type: Experimental
description: Patients undergo bilateral screening DM with standard CC and MLO views at baseline, 12, 24, 36, and 48 months if pre-menopausal or at baseline, 24, and 48 months if post-menopausal.
arm group label: Arm B (digital tomosynthesis mammography)
arm group type: Experimental
description: Patients undergo manufacturer-defined screening TM at baseline, 12, 24, 36, and 48 months if pre-menopausal or at baseline, 24, and 48 months if post-menopausal.
intervention type: Procedure
intervention name: Digital Mammography
description: Undergo DM
arm group label: Arm A (digital mammography)
other name: Full Field Digital Mammography
other name: FFDM
intervention type: Procedure
intervention name: Digital Tomosynthesis Mammography
description: Undergo TM
arm group label: Arm B (digital tomosynthesis mammography)
other name: DBT
other name: Digital Breast Tomosynthesis
other name: Digital Tomosynthesis of the Breast
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Arm A (digital mammography)
arm group label: Arm B (digital tomosynthesis mammography)
other name: Biomarker analysis
other name: genetic analysis
other name: PAM50
criteria: 
gender: Female
minimum age: 45 Years
maximum age: 74 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Etta Pisano
role: Principal Investigator
affiliation: ECOG-ACRIN Cancer Research Group
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facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: Argentina
country: Canada
country: Korea, Republic of
country: Puerto Rico
country: United States
responsible party type: Sponsor