xml: <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/NCT05982496</url>
    </required_header>
    <id_info>
      <org_study_id>FESTA</org_study_id>
      <nct_id>NCT05982496</nct_id>
    </id_info>
    <brief_title>18F FES-PET/MRI for Tailoring Treatment of Luminal A and Lobular Breast Cancer</brief_title>
    <acronym>FESTA</acronym>
    <official_title>18F-FES PET/MRI for Tailoring Treatment of Luminal A and Lobular Breast Cancer: a Phase II Prospective Cohort Study Evaluating the Performance of FES PET/MRI in Axillary Staging Compared With Axillary Surgery</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Università Vita-Salute San Raffaele</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Associazione Italiana per la Ricerca sul Cancro</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>IRCCS San Raffaele</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Università Vita-Salute San Raffaele</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>
        Study hypothesis is that combining the advantages of hybrid PET/MRI and the high&#xD;
        sensitivity/specificity of 16-alpha-18F-fluoro-17-beta-estradiol(FES), a radiolabeled form of&#xD;
        estrogen binding to functionally active ER, the investigators could obtain a reliable,&#xD;
        non-invasive, operator-independent, one-stage imaging method for staging LumA and ER-positive&#xD;
        Lobular tumours.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a single-centre prospective cohort study where patients with LumA and ER-positive Lob&#xD;
        will be enrolled in 4 cohorts undergoing: primary surgery; induction endocrine therapy;&#xD;
        neoadjuvant chemotherapy; systemic therapy for metastatic disease. For the purpose of the&#xD;
        study an additional FES PET/MRI exam will be performed at baseline for local and systemic&#xD;
        staging and a second exam after systemic therapy. Correlations between FES PET/MRI parameters&#xD;
        and pathology, gene expression and FDG PET parameters, when available, will be investigated.&#xD;
        Aim 1: Evaluating the performance of FES PET/MRI in axillary staging compared with axillary&#xD;
        surgery. Aim 2: Evaluating potential correlations between changes in FES uptake and changes&#xD;
        in proliferation index after 3 weeks of endocrine therapy before surgery. Aim 3: Evaluating&#xD;
        the performance of FES PET/MRI in staging of patients undergoing systemic therapy in&#xD;
        comparison with standard imaging. Additionally, biological determinants of tumor&#xD;
        heterogeneity will be investigated.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 15, 2023</start_date>
    <completion_date type="Anticipated">November 1, 2028</completion_date>
    <primary_completion_date type="Anticipated">May 15, 2027</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>Cohort A&#xD;
  candidates to surgery as first treatment regardless of cN&#xD;
  ER+ Her2 negative BC with ki67&gt;10% Cohort B&#xD;
  ER positive BC treated with induction ET Cohort C&#xD;
  candidates to neoadjuvant chemotherapy Cohort D&#xD;
  Metastatic LumA or ER-positive Lob BC, at first diagnosis or in progression</intervention_model_description>
      <primary_purpose>Diagnostic</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Sensitivity of FES PET/MRI in detecting macrometastatic axillary lymph nodes</measure>
      <time_frame>Day 50</time_frame>
      <description>Ability of FES PET/MRI to detect macrometastatic (tumor deposit&gt;2mm) axillary lymph nodes in BC patients with LumA or Lob who are candidates to primary surgery.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Changes in Standard Uptake Value (SUV) of FES in patients undergoing induction Endocrine Treatment (ET)</measure>
      <time_frame>Day 0 and Day 50</time_frame>
      <description>To investigate the potential correlation between Δ(FES SUV) and Δ(Ki-67 as proliferation index) after induction ET in luminal BC.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>FES PET/MRI sensitivity compared to that of standard imaging in patients undergoimg systemic therapy for neoadjuvant purposes or for metastatic disease.</measure>
      <time_frame>Day 0</time_frame>
      <description>Results from FES PET/MRI will be compared with those from standard imaging in terms of sensitivity and number of lesions detected.</description>
    </other_outcome>
    <other_outcome>
      <measure>FES PET/MRI ability to predict tumor response or no response to therapy</measure>
      <time_frame>Day 180</time_frame>
      <description>Results of FES PET/MRI after two cycles of therapy will be compared to final pathology (cohort C) or standard imaging at 6 months (cohort D)</description>
    </other_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">221</enrollment>
    <condition>Breast Cancer Female</condition>
    <condition>Lobular Breast Carcinoma</condition>
    <condition>PET/MRI</condition>
    <condition>Axillary Lymphadenopathy</condition>
    <condition>Luminal A Breast Cancer</condition>
    <arm_group>
      <arm_group_label>Cohort A</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Candidates to surgery as first treatment regardless of cN&#xD;
  ER+ Her2 negative BC with ki67&gt;10%</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cohort B</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>• ER positive BC treated with induction ET</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cohort C</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>• Candidates to neoadjuvant chemotherapy</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cohort D</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>• Metastatic LumA or ER-positive Lob BC, at first diagnosis or in progression</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>FES</intervention_name>
      <description>16-alpha-18F-fluoro-17-beta-estradiol(FES) is a radiolabeled form of estrogen binding to functionally active ER which will be used as radiotracer for the PET/MRI exam</description>
      <arm_group_label>Cohort A</arm_group_label>
      <arm_group_label>Cohort B</arm_group_label>
      <arm_group_label>Cohort C</arm_group_label>
      <arm_group_label>Cohort D</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>PET/MRI A</intervention_name>
      <description>An additional FES PET/MRI will be performed before surgery.</description>
      <arm_group_label>Cohort A</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>PET/MRI B</intervention_name>
      <description>Two additional PET/MRI will be performed before and after induction ET.</description>
      <arm_group_label>Cohort B</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>PET/MRI C</intervention_name>
      <description>Two additional PET/MRI will be performed before and after two cycles of neoadjuvant chemotherapy.</description>
      <arm_group_label>Cohort C</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>PET/MRI D</intervention_name>
      <description>Two additional PET/MRI will be performed before and after two cycles of systemic therapy.</description>
      <arm_group_label>Cohort D</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Genetic</intervention_type>
      <intervention_name>Translational analysis</intervention_name>
      <description>Selected cases of heterogeneous tumors on imaging will be also investigated on pathology, imaging, genomic and radiomic levels.</description>
      <arm_group_label>Cohort A</arm_group_label>
      <arm_group_label>Cohort B</arm_group_label>
      <arm_group_label>Cohort C</arm_group_label>
      <arm_group_label>Cohort D</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Female patients, age&gt;= 18 yrs, diagnosed with primary or advanced breast cancer&#xD;
  &#xD;
            -  LumA or ER-positive Lobular subtypes Cohort A&#xD;
  &#xD;
                 -  candidates to surgery as first treatment regardless of cN&#xD;
  &#xD;
                 -  ER-positive Her2 negative BC with ki67&gt;10% Cohort B&#xD;
  &#xD;
                 -  ER positive BC treated with induction ET Cohort C&#xD;
  &#xD;
                 -  candidates to neoadjuvant chemotherapy Cohort D&#xD;
  &#xD;
                 -  Metastatic LumA or ER-positive Lob BC, at first diagnosis or in progression&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  ER-negative tumors&#xD;
  &#xD;
            -  Pregnancy;&#xD;
  &#xD;
            -  Contraindication to PET;&#xD;
  &#xD;
            -  Contraindication to MRI;&#xD;
  &#xD;
            -  Claustrophobia;&#xD;
  &#xD;
            -  Allergy to the MR contrast agent;&#xD;
  &#xD;
            -  Severe renal insufficiency&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Rosa Di Micco, MD</last_name>
      <phone>+39022643</phone>
      <phone_ext>4565</phone_ext>
      <email>dimicco.rosa@hsr.it</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Nicole Rotmensz, MSc</last_name>
      <phone>Cohort A • candidates to surge</phone>
      <phone_ext>5650</phone_ext>
      <email>rotmensz.nicole@hsr.it</email>
    </overall_contact_backup>
    <reference>
      <citation>Franquet E, Park H. Molecular imaging in oncology: Common PET/CT radiopharmaceuticals and applications. Eur J Radiol Open. 2022 Nov 24;9:100455. doi: 10.1016/j.ejro.2022.100455. eCollection 2022.</citation>
      <PMID>36439301</PMID>
    </reference>
    <reference>
      <citation>Schumacher K, Inciardi M, O'Neil M, Wagner JL, Shah I, Amin AL, Balanoff CR, Larson KE. Is axillary imaging for invasive lobular carcinoma accurate in determining clinical node staging? Breast Cancer Res Treat. 2021 Feb;185(3):567-572. doi: 10.1007/s10549-020-06047-w. Epub 2021 Jan 3.</citation>
      <PMID>33389408</PMID>
    </reference>
    <reference>
      <citation>Iorfida M, Maiorano E, Orvieto E, Maisonneuve P, Bottiglieri L, Rotmensz N, Montagna E, Dellapasqua S, Veronesi P, Galimberti V, Luini A, Goldhirsch A, Colleoni M, Viale G. Invasive lobular breast cancer: subtypes and outcome. Breast Cancer Res Treat. 2012 Jun;133(2):713-23. doi: 10.1007/s10549-012-2002-z. Epub 2012 Mar 8.</citation>
      <PMID>22399188</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 5, 2023</study_first_submitted>
    <study_first_submitted_qc>August 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 8, 2023</study_first_posted>
    <last_update_submitted>August 8, 2023</last_update_submitted>
    <last_update_submitted_qc>August 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Università Vita-Salute San Raffaele</investigator_affiliation>
      <investigator_full_name>Rosa Di Micco, MD</investigator_full_name>
      <investigator_title>Principal Investigator</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Breast Neoplasms</mesh_term>
      <mesh_term>Carcinoma, Lobular</mesh_term>
      <mesh_term>Lymphadenopathy</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05982496
  org study id: FESTA
  nct id: NCT05982496
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Study hypothesis is that combining the advantages of hybrid PET/MRI and the high
        sensitivity/specificity of 16-alpha-18F-fluoro-17-beta-estradiol(FES), a radiolabeled form of
        estrogen binding to functionally active ER, the investigators could obtain a reliable,
        non-invasive, operator-independent, one-stage imaging method for staging LumA and ER-positive
        Lobular tumours.
  This is a single-centre prospective cohort study where patients with LumA and ER-positive Lob
        will be enrolled in 4 cohorts undergoing: primary surgery; induction endocrine therapy;
        neoadjuvant chemotherapy; systemic therapy for metastatic disease. For the purpose of the
        study an additional FES PET/MRI exam will be performed at baseline for local and systemic
        staging and a second exam after systemic therapy. Correlations between FES PET/MRI parameters
        and pathology, gene expression and FDG PET parameters, when available, will be investigated.
        Aim 1: Evaluating the performance of FES PET/MRI in axillary staging compared with axillary
        surgery. Aim 2: Evaluating potential correlations between changes in FES uptake and changes
        in proliferation index after 3 weeks of endocrine therapy before surgery. Aim 3: Evaluating
        the performance of FES PET/MRI in staging of patients undergoing systemic therapy in
        comparison with standard imaging. Additionally, biological determinants of tumor
        heterogeneity will be investigated.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  intervention model description: Cohort A
  candidates to surgery as first treatment regardless of cN
  ER+ Her2 negative BC with ki67>10% Cohort B
  ER positive BC treated with induction ET Cohort C
  candidates to neoadjuvant chemotherapy Cohort D
  Metastatic LumA or ER-positive Lob BC, at first diagnosis or in progression
  primary purpose: Diagnostic
  masking: None (Open Label)
  measure: Sensitivity of FES PET/MRI in detecting macrometastatic axillary lymph nodes
  time frame: Day 50
  description: Ability of FES PET/MRI to detect macrometastatic (tumor deposit>2mm) axillary lymph nodes in BC patients with LumA or Lob who are candidates to primary surgery.
  measure: Changes in Standard Uptake Value (SUV) of FES in patients undergoing induction Endocrine Treatment (ET)
  time frame: Day 0 and Day 50
  description: To investigate the potential correlation between Δ(FES SUV) and Δ(Ki-67 as proliferation index) after induction ET in luminal BC.
  measure: FES PET/MRI sensitivity compared to that of standard imaging in patients undergoimg systemic therapy for neoadjuvant purposes or for metastatic disease.
  time frame: Day 0
  description: Results from FES PET/MRI will be compared with those from standard imaging in terms of sensitivity and number of lesions detected.
  measure: FES PET/MRI ability to predict tumor response or no response to therapy
  time frame: Day 180
  description: Results of FES PET/MRI after two cycles of therapy will be compared to final pathology (cohort C) or standard imaging at 6 months (cohort D)
  arm group label: Cohort A
  arm group type: Experimental
  description: Candidates to surgery as first treatment regardless of cN
  ER+ Her2 negative BC with ki67>10%
  arm group label: Cohort B
  arm group type: Experimental
  description: • ER positive BC treated with induction ET
  arm group label: Cohort C
  arm group type: Experimental
  description: • Candidates to neoadjuvant chemotherapy
  arm group label: Cohort D
  arm group type: Experimental
  description: • Metastatic LumA or ER-positive Lob BC, at first diagnosis or in progression
  intervention type: Drug
  intervention name: FES
  description: 16-alpha-18F-fluoro-17-beta-estradiol(FES) is a radiolabeled form of estrogen binding to functionally active ER which will be used as radiotracer for the PET/MRI exam
  arm group label: Cohort A
  arm group label: Cohort B
  arm group label: Cohort C
  arm group label: Cohort D
  intervention type: Procedure
  intervention name: PET/MRI A
  description: An additional FES PET/MRI will be performed before surgery.
  arm group label: Cohort A
  intervention type: Procedure
  intervention name: PET/MRI B
  description: Two additional PET/MRI will be performed before and after induction ET.
  arm group label: Cohort B
  intervention type: Procedure
  intervention name: PET/MRI C
  description: Two additional PET/MRI will be performed before and after two cycles of neoadjuvant chemotherapy.
  arm group label: Cohort C
  intervention type: Procedure
  intervention name: PET/MRI D
  description: Two additional PET/MRI will be performed before and after two cycles of systemic therapy.
  arm group label: Cohort D
  intervention type: Genetic
  intervention name: Translational analysis
  description: Selected cases of heterogeneous tumors on imaging will be also investigated on pathology, imaging, genomic and radiomic levels.
  arm group label: Cohort A
  arm group label: Cohort B
  arm group label: Cohort C
  arm group label: Cohort D
  criteria: 
  gender: Female
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Rosa Di Micco, MD
  phone: +39022643
  phone ext: 4565
  email: dimicco.rosa@hsr.it
  last name: Nicole Rotmensz, MSc
  phone: Cohort A • candidates to surge
  phone ext: 5650
  email: rotmensz.nicole@hsr.it
  citation: Franquet E, Park H. Molecular imaging in oncology: Common PET/CT radiopharmaceuticals and applications. Eur J Radiol Open. 2022 Nov 24;9:100455. doi: 10.1016/j.ejro.2022.100455. eCollection 2022.
  PMID: 36439301
  citation: Schumacher K, Inciardi M, O'Neil M, Wagner JL, Shah I, Amin AL, Balanoff CR, Larson KE. Is axillary imaging for invasive lobular carcinoma accurate in determining clinical node staging? Breast Cancer Res Treat. 2021 Feb;185(3):567-572. doi: 10.1007/s10549-020-06047-w. Epub 2021 Jan 3.
  PMID: 33389408
  citation: Iorfida M, Maiorano E, Orvieto E, Maisonneuve P, Bottiglieri L, Rotmensz N, Montagna E, Dellapasqua S, Veronesi P, Galimberti V, Luini A, Goldhirsch A, Colleoni M, Viale G. Invasive lobular breast cancer: subtypes and outcome. Breast Cancer Res Treat. 2012 Jun;133(2):713-23. doi: 10.1007/s10549-012-2002-z. Epub 2012 Mar 8.
  PMID: 22399188
  responsible party type: Principal Investigator
  investigator affiliation: Università Vita-Salute San Raffaele
  investigator full name: Rosa Di Micco, MD
  investigator title: Principal Investigator
  mesh term: Breast Neoplasms
  mesh term: Carcinoma, Lobular
  mesh term: Lymphadenopathy