<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/NCT04461808</url>
  </required_header>
  <id_info>
    <org_study_id>RF-2016-02363686</org_study_id>
    <nct_id>NCT04461808</nct_id>
  </id_info>
  <brief_title>Tomosynthesis as Primary Test for Breast Cancer Screening</brief_title>
  <acronym>MAITA</acronym>
  <official_title>Tomosynthesis as Primary Test for Breast Cancer Screening: A Multicenter Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Azienda Unità Sanitaria Locale Reggio Emilia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AULSS 9 Scaligera di Verona</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>IRCCS Policlinico S. Donato, Milano</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Azienda Ospedaliera Universitaria Integrata Verona</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Azienda Unità Sanitaria Locale Reggio Emilia</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Randomized trial comparing tomosynthesis plus synthetic 2D Mammography vs Digital Mammography&#xD;
      in respect to incidence of advanced cancers (interval and following round) and interval&#xD;
      cancers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a companion study of the other Italian studies on tomosyntesis as primary screening&#xD;
      test for breast cancer: RETomo (NCT02698202), PROTEUS (NCT02590315), IMPETO (NCT03587259).&#xD;
      The investigators conduct a randomized trial in three centres with a protocol that is similar&#xD;
      to that of the other three studies. As for IMPETO and differently from the RETomo and PROTEUS&#xD;
      studies, the intervention will be tomosynthesis + synthetic 2D.&#xD;
&#xD;
      In the three centres about 8000 women will be recruited (4000 in the experimental arm and&#xD;
      4000 in the control arm).&#xD;
&#xD;
      The study will compare the performance of tomosynthesis plus synthetic 2D vs digital&#xD;
      mammography in respect to incidence of advanced cancers (interval and following round) and&#xD;
      interval cancers. Women 50 to 65 years old will be screened once according to randomization&#xD;
      arm for one round, then all will be screened with digital mammography after two years.&#xD;
&#xD;
      The investigators also will measure detection rates, specificity, interval cancers, advanced&#xD;
      cancers occurring as interval cancers or at subsequent screens and allowing to estimate&#xD;
      excess overdiagnosis comparing overall cumulative incidence after two or three rounds of&#xD;
      screening.&#xD;
&#xD;
      Women will be asked for informed consent when they attend the mammography. If they accept&#xD;
      they will be randomised to one of the two arms.&#xD;
&#xD;
      All examinations will be read by two independent radiologists, in case of discordance a third&#xD;
      reading is asked.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 15, 2019</start_date>
  <completion_date type="Anticipated">June 30, 2026</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2024</primary_completion_date>
  <phase>N/A</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>Women 45-65 participating in the mammographic screening program will be randomized to one round of screening with tomosynthesis + synthetic 2D or with digital mammography. Then all women will be re-screened after 2 years (1 year for women 45-49) for at least one round with digital mammography.</intervention_model_description>
    <primary_purpose>Screening</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>It is not possible to mask the intervention for the patient, care provider, and investigator.&#xD;
Only the assessment of one of the two co-primary outcomes, i.e. cumulative incidence of advanced breast cancer after the first round of screening, can be masked. This will be obtained through a blind review of an external panel of pathologists and radiologists reviewing cases retrieved by cancer registries.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>advanced cancer incidence</measure>
    <time_frame>2 years (+9 months to complete second round assessment)</time_frame>
    <description>cumulative incidence of T2+ cancers after first screening round</description>
  </primary_outcome>
  <primary_outcome>
    <measure>advanced cancer incidence</measure>
    <time_frame>4 years (+9 months to complete third round assessment)</time_frame>
    <description>cumulative incidence of T2+ cancers after first screening round</description>
  </primary_outcome>
  <primary_outcome>
    <measure>interval cancer incidence</measure>
    <time_frame>2 years for 50-65 years old women</time_frame>
    <description>incidence of cancers occurring after a negative screening test and before the next scheduled screening round. Outcome 3 and 4 will are combined in one single outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>interval cancer incidence</measure>
    <time_frame>1 year for 45-49 years old women</time_frame>
    <description>incidence of cancers occurring after a negative screening test and before the next scheduled screening round. Outcome 3 and 4 will are combined in one single outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>overall cumulative incidence</measure>
    <time_frame>2 years (+9 months to complete second round assessment)</time_frame>
    <description>overall cumulative incidence of breast cancer, including ductal carcinoma in situ. This outcome is a proxy of the excess over-diagnosis eventually induced by tomosynthesis compared with digital mammography.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>overall cumulative incidence</measure>
    <time_frame>4 years (+9 months to complete second round assessment)</time_frame>
    <description>overall cumulative incidence of breast cancer, including ductal carcinoma in situ. This outcome is a proxy of the excess over-diagnosis eventually induced by tomosynthesis compared with digital mammography.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>detection rate</measure>
    <time_frame>This outcome is measured at the baseline screening. cancer diagnosed within 9 months will be considered</time_frame>
    <description>cancer detected by the screening round on total screened women</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>recall rate</measure>
    <time_frame>This outcome is measured at the baseline screening.</time_frame>
    <description>number of women referred to assessment after the first leve screening test on total screened women</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>positive predictive value</measure>
    <time_frame>This outcome is measured at the baseline screening. cancer diagnosed within 9 months will be considered</time_frame>
    <description>proportion of cancer among women recalled for assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Detection rate of ductal carcinoma in situ</measure>
    <time_frame>This outcome is measured at the baseline screening. cancer diagnosed within 9 months will be considered</time_frame>
    <description>ductal carcinoma in situ detected by the screening round on total screened women</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>biopsy rate</measure>
    <time_frame>This outcome is measured at the baseline screening.</time_frame>
    <description>number of women undergoing biopsy after the first leve screening test on total screened women</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>x-ray dose</measure>
    <time_frame>This outcome is measured at the baseline screening.</time_frame>
    <description>average glandular dose receive by women during first level test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>reading time</measure>
    <time_frame>This outcome is measured at the baseline screening.</time_frame>
    <description>time needed to read an imaging first level examination</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">8000</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Tomosynthesis + synthetic 2D</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Women will be screened for one round with tomosynthesis + synthetic 2D, two projections, double reading with consensus or arbitration, according to local protocols, for discordant readings.&#xD;
After two years (one years for women 45-49 yo) women will be re-screened with digital mammography.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Digital Mammography</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Women will be screened for digital mammography, two projections, double reading with consensus or arbitration, according to local protocols, for discordant readings.&#xD;
After two years (one years for women 45-49 yo) women will be re-screened with digital mammography.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>tomosynthesis + synthetic 2D</intervention_name>
    <description>Women will be screened for one round with tomosynthesis + synthetic 2D, two projections, double reading with consensus or arbitration, according to local protocols, for discordant readings.&#xD;
After two years (one years for women 45-49 yo) women will be re-screened with digital mammography.</description>
    <arm_group_label>Tomosynthesis + synthetic 2D</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>digital mammography</intervention_name>
    <description>Women will be screened for one round digital mammography, two projections, double reading with consensus or arbitration, according to local protocols, for discordant readings.&#xD;
After two years (one years for women 45-49 yo) women will be re-screened with digital mammography.</description>
    <arm_group_label>Digital Mammography</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women scheduled for a new round of mammographic screening&#xD;
&#xD;
          -  resident in the province&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  previous breast cancer diagnosis&#xD;
&#xD;
          -  pregnancy or suspicion of pregnancy&#xD;
&#xD;
          -  presence of BRCA1/2 gene mutation&#xD;
&#xD;
          -  Previous Digital Breast Tomosynthesis performed&#xD;
&#xD;
          -  unable to understand informed consent&#xD;
&#xD;
          -  chemotherapy in progress&#xD;
&#xD;
          -  presence of breast implant&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Paolo Giorgi Rossi, PhD</last_name>
    <phone>+39335499770</phone>
    <email>paolo.giorgirossi@ausl.re.it</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Pierpaolo Pattacini, MD</last_name>
    <phone>+390522296369</phone>
    <email>pierpaolo.pattacini@asul.re.it</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>IRCCS Policlinico San Donato</name>
      <address>
        <city>Milano</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Francesco Sardanelli, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia</name>
      <address>
        <city>Reggio Emilia</city>
        <zip>42122</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Paolo Giorgi Rossi, PhD</last_name>
      <phone>+39335499770</phone>
      <email>paolo.giorgirossi@ausl.re.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria Integrata</name>
      <address>
        <city>Verona</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stefania Montemezzi, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Azienda Ulss 9 Scaligera</name>
      <address>
        <city>Verona</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Francesca Fornasa, MD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 8, 2020</study_first_posted>
  <last_update_submitted>July 7, 2020</last_update_submitted>
  <last_update_submitted_qc>July 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>breast cancer screening</keyword>
  <keyword>tomosynthesis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <!-- 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/NCT04461808
org study id: RF-2016-02363686
nct id: NCT04461808
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Randomized trial comparing tomosynthesis plus synthetic 2D Mammography vs Digital Mammography
      in respect to incidence of advanced cancers (interval and following round) and interval
      cancers.
This is a companion study of the other Italian studies on tomosyntesis as primary screening
      test for breast cancer: RETomo (NCT02698202), PROTEUS (NCT02590315), IMPETO (NCT03587259).
      The investigators conduct a randomized trial in three centres with a protocol that is similar
      to that of the other three studies. As for IMPETO and differently from the RETomo and PROTEUS
      studies, the intervention will be tomosynthesis + synthetic 2D.

      In the three centres about 8000 women will be recruited (4000 in the experimental arm and
      4000 in the control arm).

      The study will compare the performance of tomosynthesis plus synthetic 2D vs digital
      mammography in respect to incidence of advanced cancers (interval and following round) and
      interval cancers. Women 50 to 65 years old will be screened once according to randomization
      arm for one round, then all will be screened with digital mammography after two years.

      The investigators also will measure detection rates, specificity, interval cancers, advanced
      cancers occurring as interval cancers or at subsequent screens and allowing to estimate
      excess overdiagnosis comparing overall cumulative incidence after two or three rounds of
      screening.

      Women will be asked for informed consent when they attend the mammography. If they accept
      they will be randomised to one of the two arms.

      All examinations will be read by two independent radiologists, in case of discordance a third
      reading is asked.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Women 45-65 participating in the mammographic screening program will be randomized to one round of screening with tomosynthesis + synthetic 2D or with digital mammography. Then all women will be re-screened after 2 years (1 year for women 45-49) for at least one round with digital mammography.
primary purpose: Screening
masking: Single (Outcomes Assessor)
masking description: It is not possible to mask the intervention for the patient, care provider, and investigator.
Only the assessment of one of the two co-primary outcomes, i.e. cumulative incidence of advanced breast cancer after the first round of screening, can be masked. This will be obtained through a blind review of an external panel of pathologists and radiologists reviewing cases retrieved by cancer registries.
measure: advanced cancer incidence
time frame: 2 years (+9 months to complete second round assessment)
description: cumulative incidence of T2+ cancers after first screening round
measure: advanced cancer incidence
time frame: 4 years (+9 months to complete third round assessment)
description: cumulative incidence of T2+ cancers after first screening round
measure: interval cancer incidence
time frame: 2 years for 50-65 years old women
description: incidence of cancers occurring after a negative screening test and before the next scheduled screening round. Outcome 3 and 4 will are combined in one single outcome.
measure: interval cancer incidence
time frame: 1 year for 45-49 years old women
description: incidence of cancers occurring after a negative screening test and before the next scheduled screening round. Outcome 3 and 4 will are combined in one single outcome.
measure: overall cumulative incidence
time frame: 2 years (+9 months to complete second round assessment)
description: overall cumulative incidence of breast cancer, including ductal carcinoma in situ. This outcome is a proxy of the excess over-diagnosis eventually induced by tomosynthesis compared with digital mammography.
measure: overall cumulative incidence
time frame: 4 years (+9 months to complete second round assessment)
description: overall cumulative incidence of breast cancer, including ductal carcinoma in situ. This outcome is a proxy of the excess over-diagnosis eventually induced by tomosynthesis compared with digital mammography.
measure: detection rate
time frame: This outcome is measured at the baseline screening. cancer diagnosed within 9 months will be considered
description: cancer detected by the screening round on total screened women
measure: recall rate
time frame: This outcome is measured at the baseline screening.
description: number of women referred to assessment after the first leve screening test on total screened women
measure: positive predictive value
time frame: This outcome is measured at the baseline screening. cancer diagnosed within 9 months will be considered
description: proportion of cancer among women recalled for assessment
measure: Detection rate of ductal carcinoma in situ
time frame: This outcome is measured at the baseline screening. cancer diagnosed within 9 months will be considered
description: ductal carcinoma in situ detected by the screening round on total screened women
measure: biopsy rate
time frame: This outcome is measured at the baseline screening.
description: number of women undergoing biopsy after the first leve screening test on total screened women
measure: x-ray dose
time frame: This outcome is measured at the baseline screening.
description: average glandular dose receive by women during first level test
measure: reading time
time frame: This outcome is measured at the baseline screening.
description: time needed to read an imaging first level examination
arm group label: Tomosynthesis + synthetic 2D
arm group type: Experimental
description: Women will be screened for one round with tomosynthesis + synthetic 2D, two projections, double reading with consensus or arbitration, according to local protocols, for discordant readings.
After two years (one years for women 45-49 yo) women will be re-screened with digital mammography.
arm group label: Digital Mammography
arm group type: Active Comparator
description: Women will be screened for digital mammography, two projections, double reading with consensus or arbitration, according to local protocols, for discordant readings.
After two years (one years for women 45-49 yo) women will be re-screened with digital mammography.
intervention type: Diagnostic Test
intervention name: tomosynthesis + synthetic 2D
description: Women will be screened for one round with tomosynthesis + synthetic 2D, two projections, double reading with consensus or arbitration, according to local protocols, for discordant readings.
After two years (one years for women 45-49 yo) women will be re-screened with digital mammography.
arm group label: Tomosynthesis + synthetic 2D
intervention type: Diagnostic Test
intervention name: digital mammography
description: Women will be screened for one round digital mammography, two projections, double reading with consensus or arbitration, according to local protocols, for discordant readings.
After two years (one years for women 45-49 yo) women will be re-screened with digital mammography.
arm group label: Digital Mammography
criteria: 
gender: Female
minimum age: 45 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Paolo Giorgi Rossi, PhD
phone: +39335499770
email: paolo.giorgirossi@ausl.re.it
last name: Pierpaolo Pattacini, MD
phone: +390522296369
email: pierpaolo.pattacini@asul.re.it
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Italy
responsible party type: Sponsor
mesh term: Breast Neoplasms