<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/NCT04460807</url>
  </required_header>
  <id_info>
    <org_study_id>56UCS2017</org_study_id>
    <secondary_id>2018-000693-30</secondary_id>
    <nct_id>NCT04460807</nct_id>
  </id_info>
  <brief_title>Exemestane in Hormone Receptor Positive High Grade Ovarian Cancer</brief_title>
  <acronym>EXPERT</acronym>
  <official_title>EXemestane in Progesterone and/or Estrogen Receptor Positive Epithelial Ovarian Cancer: A Randomized Phase III Trial, EXPERT</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ente Ospedaliero Ospedali Galliera</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Istituto Di Ricerche Farmacologiche Mario Negri</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Fondazione Policlinico Universitario Agostino Gemelli IRCCS</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Federation of Italian Cooperative Oncology Groups</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Ente Ospedaliero Ospedali Galliera</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this Italian, multicenter, randomized, double-blind, placebo controlled, phase III study&#xD;
      the efficacy of exemestane will be evaluated in addition to the standard front line treatment&#xD;
      in patients with hormone-receptor-positive high grade serous or endometrioid Epithelian&#xD;
      Ovarian Cancer (EOC). The patients enrolled in the EXPERT trial will receive exemestane or&#xD;
      placebo in addition to standard treatment. Patients and investigators will be blinded to&#xD;
      study treatment.&#xD;
&#xD;
      The hypothesis underlying the proposed clinical trial is that exemestane added to standard&#xD;
      first line therapy will significantly prolong median progression free survival (PFS).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Estrogen and Progesterone play a role in promoting EOC growth, metastasis, and progression.&#xD;
      Recent data show that ER and PgR expression is frequent in high grade EOC and has prognostic&#xD;
      significance. A large meta-analysis showed a clinical benefit with any endocrine treatment,&#xD;
      and in particular for aromatase inhibitors (AIs), with a greatere benefit for ER+ and/or PgR+&#xD;
      patients and platinum sensitive tumors. Moreover, the analysis of a few randomized clinical&#xD;
      trials (RCTs) showed a reduced mortality with endocrine therapy in EOC, suggesting that ER&#xD;
      and PgR have a predictive role and that inhibition of their activation could therefore be a&#xD;
      treatment option for EOC.&#xD;
&#xD;
      Exemestane is a well-tolerated and effective AI in endocrine sensitive breast cancer which&#xD;
      inhibits the production of Estrogens by the adipose tissue in postmenopausal women.&#xD;
&#xD;
      In this Italian, multicentre, randomized, double-blind, placebo controlled, phase III study&#xD;
      will be assessed the efficacy of exemestane versus placebo in addition to the standard front&#xD;
      line treatment in patients with high grade serous or endometrioid EOC, IHC positive (≥ 10%)&#xD;
      ER or PgR disease, stage IIB - IV according to the FIGO classification.&#xD;
&#xD;
      The primary objective of the study is to test the superiority of exemestane over placebo in&#xD;
      addition to the standard front line treatment in terms of PFS.&#xD;
&#xD;
      Secondary Objectives are:&#xD;
&#xD;
        1. to test whether the percent expression of ER and PgR is predictive of the effect of&#xD;
           exemestane on PFS;&#xD;
&#xD;
        2. to test whether the addition of exemestane to the standard front line treatment can&#xD;
           prolong Overall Survival (OS);&#xD;
&#xD;
        3. to evaluate objective response rate Overall Response Rate (ORR) of experimental&#xD;
           treatment compared with the standard one;&#xD;
&#xD;
        4. to assess whether the effect of exemestane is affected by the proliferative index Ki67;&#xD;
&#xD;
        5. to evaluate the effect of exemestane on Quality of Life (QoL);&#xD;
&#xD;
        6. to evaluate the compliance to the study treatment;&#xD;
&#xD;
        7. to evaluate the safety profile of the experimental treatment compared with the standard&#xD;
           one.&#xD;
&#xD;
      Study design: a total of 468 subjects (234 per Arm) will be randomized in a 1:1 ratio to&#xD;
      receive either standard chemotherapy treatment plus exemestane (Experimental arm) or standard&#xD;
      chemotherapy plus placebo (Control arm). Exemestane/placebo will be self-administered as a&#xD;
      single oral tablet of 25 mg/day until disease progression, unacceptable toxicity or&#xD;
      physician/patient decision to withdraw, whichever comes first. Radiological disease&#xD;
      assessments and CA125 will be performed at baseline and every 4 months from randomization,&#xD;
      until end of study or disease progression whichever comes first. Safety assessments will be&#xD;
      performed at each cycle during standard chemotherapy treatment, then at each study visit, up&#xD;
      to 30 days after the last Experimental Treatment administration.Quality of Life will be&#xD;
      assessed by a menopause-specific questionnaire, administered to patients at baseline (T0), at&#xD;
      12 months (T1) and at disease progression (T2). For patients who have signed the specific&#xD;
      informed consent, tissues and blood samples will be collected.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">February 13, 2020</start_date>
  <completion_date type="Anticipated">February 2023</completion_date>
  <primary_completion_date type="Anticipated">October 2022</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>Up to 20 months</time_frame>
    <description>PFS id defined for each patient as the time from the date of randomization to the date of local or regional relapse, distant metastasis, second primary malignancy or death from any cause, whichever comes first. Patients not recurred, progressed or died while on study or lost to follow-up will be censored at their last disease assessment date.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>Up to 20 months</time_frame>
    <description>OS is defined for each patient as the time from the date of randomization to the date of death from any cause. Patients not reported as having died at the end of the study will be censored at the date they were last known to be alive.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>a CT-scan will be performed every 4 months. Up to 20 months from last patients randomized</time_frame>
    <description>ORR is defined as the number of patients who will experience a complete or partial response divided by the number of patients randomized with at least one target lesion at baseline. Each patient will be assigned the best response ever recorded during the trial</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life: Menopause Quality of Life (MENQoL) questionnaire</measure>
    <time_frame>Up to 20 months</time_frame>
    <description>The effect of study treatment will be assessed based on the MENQOL intervention questionnaire based on 29 items divided in four domains (vasomotor, physical, psychosocial and sexual), each scored from 1 to 8 (1 means no symptom, 2 presence of the symptoms but not bothersome, 3-8 an increasing grade of discomfort). Mean changes from the baseline domain scores between treatment arms will be evaluated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compliance - Number of administered cycles</measure>
    <time_frame>Up to 20 months</time_frame>
    <description>Number of administered cycles</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compliance - Reasons for discontinuation and treatment modification</measure>
    <time_frame>Up to 20 months</time_frame>
    <description>Number of patients for each reasons</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compliance - Dose intensity</measure>
    <time_frame>Up to 20 months</time_frame>
    <description>Number of tablets taken (i.e., number of tablets given-number of tablets returned)/number of tablets that should have been taken during the treatment period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety (Adverse Events)</measure>
    <time_frame>Up to 20 months</time_frame>
    <description>Maximum toxicity grade experienced by each patient for each toxicity, proportion of patients experiencing grade 3-4 toxicity for each toxicity, type, frequency and nature of serious adverse events (SAEs).&#xD;
Proportion of patients with at least one SAE.&#xD;
Proportion of patients with at least one serious adverse drug reaction (SADR).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Circulating and tissue biomarkers</measure>
    <time_frame>Up to 20 months</time_frame>
    <description>To collect and store blood and tissue samples to create a bio-bank for the assessment of circulating and tissue biomarkers with potentially prognostic/predictive value, including the androgen receptor (AR) expression and the generation of a somatic genomic and transcriptomic atlas of epithelial ovarian cancers, to map the different molecular vulnerabilities lagging behind the single definition of each histological subtype. Data generated will allow to select molecular biomarkers with prognostic/predictive relevance, to have information of patients risk of relapse or to guide novel treatment approaches.&#xD;
These biomarker endpoints will be considered in a second phase of the study, if additional funds are available to perform the analyses.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">468</enrollment>
  <condition>Ovarian Cancer</condition>
  <arm_group>
    <arm_group_label>Exemestane</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Standard chemotherapy: paclitaxel 175 mg/m2 + carboplatin AUC 5, on day 1 every 21 days ± bevacizumab 15mg/kg, on day 1 every 21 days. Chemotherapy will be administered for 6 cycles; Bevacizumab will be administered as up to a maximum of 22 cycles. Patients unfit for standard treatment can receive a weekly schedule of treatment or monotherapy with carboplatin alone. Neoadjuvant chemotherapy is allowed in patients unfit for primary elective surgery.&#xD;
+&#xD;
Exemestane: single oral tablet of 25 mg/day until disease progression, unacceptable toxicity or physician/patient decision to withdraw, whichever comes first.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Standard chemotherapy : paclitaxel 175 mg/m2 + carboplatin AUC 5, on day 1 every 21 days ± bevacizumab 15mg/kg, on day 1 every 21 days. Chemotherapy will be administered for 6 cycles; Bevacizumab will be administered as up to a maximum of 22 cycles. Patients unfit for standard treatment can receive a weekly schedule of treatment or monotherapy with carboplatin alone. Neoadjuvant chemotherapy is allowed in patients unfit for primary elective surgery.&#xD;
+&#xD;
Placebo: single oral tablet until disease progression, unacceptable toxicity or physician/patient decision to withdraw, whichever comes first.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Exemestane</intervention_name>
    <description>Exemestane in addition to standard therapy, in Experimental arm.</description>
    <arm_group_label>Exemestane</arm_group_label>
    <other_name>Mestane</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo oral tablet</intervention_name>
    <description>Placebo in addition to standard therapy, in Control arm.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥18 years&#xD;
&#xD;
          -  Citologically or histologically confirmed high grade serous or endometrial epithelial&#xD;
             ovarian cancer, including cancer of fallopian tube and peritoneum. For patients who&#xD;
             are candidates for neoadjuvant chemotherapy, diagnosis must be documented via imaging&#xD;
             or a core tissue (not fine needle aspiration) biopsy.&#xD;
&#xD;
          -  Disease stage IIB to IV according to FIGO classification. For patients who are&#xD;
             candidates for neoadjuvant chemotherapy, stage IIB-IV should be documented via imaging&#xD;
             or a core tissue (not fine needle aspiration) biopsy.&#xD;
&#xD;
          -  Patients must have completed a surgical debulking procedure, or be candidates for&#xD;
             neoadjuvant chemotherapy. For patients enrolling after debulking surgery,&#xD;
             randomization should occur at a maximum of 12 weeks and not before 4 weeks after&#xD;
             surgery.&#xD;
&#xD;
          -  Immunoistochemically determined positivity (≥ 10%) for Progesterone and/or Estrogen&#xD;
             receptor expression, including determination on cytology smears from ascitic fluid if&#xD;
             surgery is differed.&#xD;
&#xD;
          -  Measurable or evaluable disease confirmed by radiological imaging, or histological&#xD;
             proven ovarian cancer in the absence of postoperatively measurable or evaluable&#xD;
             lesions&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group - performance status (ECOG-PS) 0-2.&#xD;
&#xD;
          -  Written, informed consent obtained prior to any study-specific procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous systemic therapy for ovarian cancer.&#xD;
&#xD;
          -  Other malignancy within the last 5 years, except for adequately treated carcinoma in&#xD;
             situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited&#xD;
             basal cell skin cancer.&#xD;
&#xD;
          -  Inadequate bone marrow, hepatic or renal functions, assessed within 7 days prior to&#xD;
             randomization.&#xD;
&#xD;
          -  Treatment with hormonal contraceptives during the previous 3 months from diagnosis.&#xD;
&#xD;
          -  Concurrent comorbidities, which contraindicates the administration of chemotherapy, or&#xD;
             endocrine therapy.&#xD;
&#xD;
          -  Pregnant or lactating patients.&#xD;
&#xD;
          -  Inability or unwillingness to swallow tablets.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Female patients</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andrea DeCensi</last_name>
    <role>Principal Investigator</role>
    <affiliation>E.O. Ospedali Galliera Genova</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Alessandra Argusti</last_name>
    <phone>00390105634188</phone>
    <email>alessandra.argusti@galliera.it</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Silvia Caviglia</last_name>
    <phone>00390105634234</phone>
    <email>silvia.caviglia@galliera.it</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>AO SS Antonio e Biagio e Cesare Arrigo</name>
      <address>
        <city>Alessandria</city>
        <state>AL</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Vittorio Fusco</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ospedale Oncologico IRCCS Bari</name>
      <address>
        <city>Bari</city>
        <state>BA</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Vito Lorusso</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ospedale degli Infermi</name>
      <address>
        <city>Biella</city>
        <state>BI</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Laura Zavallone</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>AULSS 1 Dolomiti - Ospedale &quot;Santa Maria del Prato&quot;</name>
      <address>
        <city>Feltre</city>
        <state>BL</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Romana Segati</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero Universitaria Policlinico S.Orsola-Malpighi</name>
      <address>
        <city>Bologna</city>
        <state>BO</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Claudio Zamagni</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>ASST degli Spedali Civili di Brescia</name>
      <address>
        <city>Brescia</city>
        <state>BS</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Germana Tognon</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Fondazione Poliambulanza</name>
      <address>
        <city>Brescia</city>
        <state>BS</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Chiara Abeni</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ospedale di Manerbio</name>
      <address>
        <city>Manerbio</city>
        <state>BS</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Elena Montani</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>AOU Cagliari, Policlinico Universitario</name>
      <address>
        <city>Cagliari</city>
        <state>CA</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Elena Massa</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ospedale Policlinico &quot;SS. Annunziata&quot;</name>
      <address>
        <city>Chieti</city>
        <state>CH</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Clara Natoli</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Azienda Sanitaria Locale CN2</name>
      <address>
        <city>Alba</city>
        <state>CN</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Mario Ardizzoia</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera S.Croce e Carle</name>
      <address>
        <city>Cuneo</city>
        <state>CN</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Marcella Occelli</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ospedale di Mondovì CN1</name>
      <address>
        <city>Mondovì</city>
        <state>CN</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Andrea Puppo</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ospedale Sant Anna di Como</name>
      <address>
        <city>Como</city>
        <state>CO</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Monica Giordano</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>ARNAS Garibaldi</name>
      <address>
        <city>Catania</city>
        <state>CT</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Daniela Sambataro</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera per l'emergenza Cannizzaro</name>
      <address>
        <city>Catania</city>
        <state>CT</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Giuseppe Scandurra</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS</name>
      <address>
        <city>Meldola</city>
        <state>FC</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Ugo De Giorgi</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ospedale Casa Sollievo della Sofferenza</name>
      <address>
        <city>San Giovanni Rotondo</city>
        <state>FG</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Evaristo Maiello</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>ASL 3 Ospedale Villa Scassi</name>
      <address>
        <city>Genova</city>
        <state>GE</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Manlio Mencoboni</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>IRCCS AOU San Martino - IST</name>
      <address>
        <city>Genova</city>
        <state>GE</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Serafina Mammoliti</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>ASST Lecco - Ospedale &quot;A. Manzoni&quot;</name>
      <address>
        <city>Lecco</city>
        <state>LC</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Antonio Ardizzoia</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ospedale &quot;Vito Fazzi&quot;</name>
      <address>
        <city>Lecce</city>
        <state>LE</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Graziana Ronzino</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>UOS Oncologia Ginecologica, Ospedale S. Gerardo</name>
      <address>
        <city>Monza</city>
        <state>MB</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Alberto Lissoni</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Presidio Ospedaliero Unico Av3</name>
      <address>
        <city>Macerata</city>
        <state>MC</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Nicola Battelli</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Istituto Europeo di Oncologia (IEO)</name>
      <address>
        <city>Milano</city>
        <state>MI</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Nicoletta Colombo</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>AOU Policlinico di Modena</name>
      <address>
        <city>Modena</city>
        <state>MO</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Laura Cortesi</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>A.R.N.A.S. Ospedali Civico Di Cristina Benfratelli</name>
      <address>
        <city>Palermo</city>
        <state>PA</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Livio Blasi</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ospedale &quot;Guglielmo da Saliceto&quot;</name>
      <address>
        <city>Piacenza</city>
        <state>PC</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Luigi Cavanna</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero-Universitaria Pisana</name>
      <address>
        <city>Pisa</city>
        <state>PI</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Angiolo Gadducci</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>CRO Centro di Riferimento Oncologico</name>
      <address>
        <city>Aviano</city>
        <state>PN</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Roberto Sorio</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS Policlinico San Matteo</name>
      <address>
        <city>Pavia</city>
        <state>PV</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Chiara Cassani</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Regionale San Carlo</name>
      <address>
        <city>Potenza</city>
        <state>PZ</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Domenico Bilancia</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ospedale &quot;degli Infermi&quot;</name>
      <address>
        <city>Faenza</city>
        <state>RA</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Claudia Casanova</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ospedale &quot;Umberto I&quot;</name>
      <address>
        <city>Lugo</city>
        <state>RA</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Claudia Casanova</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ospedale Santa Maria delle Croci</name>
      <address>
        <city>Ravenna</city>
        <state>RA</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Claudia Casanova</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Arcispedale Santa Maria Nuova</name>
      <address>
        <city>Reggio Emilia</city>
        <state>RE</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Alessandra Bologna</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Policlinico Umberto I, Università di Roma &quot;La Sapienza&quot;</name>
      <address>
        <city>Roma</city>
        <state>RM</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Pierluigi Benedetti Panici</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Policlinico Universitario Fondazione Agostino Gemelli</name>
      <address>
        <city>Roma</city>
        <state>RM</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Giovanni Scambia</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>ASST Valtellina e Alto Lario</name>
      <address>
        <city>Sondrio</city>
        <state>SO</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Alessandro Bertolini</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero Universitaria di Sassari</name>
      <address>
        <city>Sassari</city>
        <state>SS</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Salvatore Dessole</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Fondazione del Piemonte per l'Oncologia - IRCCS</name>
      <address>
        <city>Candiolo</city>
        <state>TO</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Massimo Aglietta</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>AO Ordine Mauriziano</name>
      <address>
        <city>Torino</city>
        <state>TO</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Annamaria Ferrero</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero-Universitaria Città della Salute e della Scienza - Ospedale Ostetrico Ginecologico Sant'Anna</name>
      <address>
        <city>Torino</city>
        <state>TO</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Dionyssios Katsaros</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Presidio Ospedaliero S. Andrea</name>
      <address>
        <city>Vercelli</city>
        <state>VC</state>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Teresa Gasparre</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Medical Oncology Division, Ente Ospedaliero Ospedali Galliera</name>
      <address>
        <city>Genova</city>
        <zip>16128</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Andrea De Censi</last_name>
      <phone>+390105634501</phone>
      <email>andrea.decensi@galliera.it</email>
    </contact>
    <contact_backup>
      <last_name>Irene Maria Briata</last_name>
      <phone>+390105634580</phone>
      <email>irene.maria.briata@galliera.it</email>
    </contact_backup>
    <investigator>
      <last_name>Andrea DeCensi</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Nicoletta Provinciali</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Istituto Nazionale Tumori - IRCCS &quot;Fondazione G.Pascale&quot;</name>
      <address>
        <city>Napoli</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Sandro Pignata</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero-Universitaria Maggiore della Carità</name>
      <address>
        <city>Novara</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Alessandra Gennari</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>April 27, 2020</study_first_submitted>
  <study_first_submitted_qc>July 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 8, 2020</study_first_posted>
  <last_update_submitted>July 3, 2020</last_update_submitted>
  <last_update_submitted_qc>July 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ente Ospedaliero Ospedali Galliera</investigator_affiliation>
    <investigator_full_name>Andrea DeCensi</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>exemestane</keyword>
  <keyword>aromatase inhibitors</keyword>
  <keyword>clinical trial, phase 3</keyword>
  <keyword>receptors, estrogen</keyword>
  <keyword>receptors, progesterone</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ovarian Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Ovarian Epithelial</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Exemestane</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Individual participant data that underlie the results reported in the primary publication of the trial will be shared (text, tables, figures, and appendices), after deidentification.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Data will be shared 3 months following the publication of the article and they will remain available for 36 months.</ipd_time_frame>
    <ipd_access_criteria>the investigators who would like to use the data have to prepare a proposal that needs to be approved the Steering committee. The aim of the access to study data needs to be specified in the proposal. Proposals should be sent to the Principal investigator (andrea.decensi@galliera.it). To gain access, data requestors will need to sign a data access agreement.</ipd_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04460807
org study id: 56UCS2017
secondary id: 2018-000693-30
nct id: NCT04460807
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
In this Italian, multicenter, randomized, double-blind, placebo controlled, phase III study
      the efficacy of exemestane will be evaluated in addition to the standard front line treatment
      in patients with hormone-receptor-positive high grade serous or endometrioid Epithelian
      Ovarian Cancer (EOC). The patients enrolled in the EXPERT trial will receive exemestane or
      placebo in addition to standard treatment. Patients and investigators will be blinded to
      study treatment.

      The hypothesis underlying the proposed clinical trial is that exemestane added to standard
      first line therapy will significantly prolong median progression free survival (PFS).
Estrogen and Progesterone play a role in promoting EOC growth, metastasis, and progression.
      Recent data show that ER and PgR expression is frequent in high grade EOC and has prognostic
      significance. A large meta-analysis showed a clinical benefit with any endocrine treatment,
      and in particular for aromatase inhibitors (AIs), with a greatere benefit for ER+ and/or PgR+
      patients and platinum sensitive tumors. Moreover, the analysis of a few randomized clinical
      trials (RCTs) showed a reduced mortality with endocrine therapy in EOC, suggesting that ER
      and PgR have a predictive role and that inhibition of their activation could therefore be a
      treatment option for EOC.

      Exemestane is a well-tolerated and effective AI in endocrine sensitive breast cancer which
      inhibits the production of Estrogens by the adipose tissue in postmenopausal women.

      In this Italian, multicentre, randomized, double-blind, placebo controlled, phase III study
      will be assessed the efficacy of exemestane versus placebo in addition to the standard front
      line treatment in patients with high grade serous or endometrioid EOC, IHC positive (≥ 10%)
      ER or PgR disease, stage IIB - IV according to the FIGO classification.

      The primary objective of the study is to test the superiority of exemestane over placebo in
      addition to the standard front line treatment in terms of PFS.

      Secondary Objectives are:

        1. to test whether the percent expression of ER and PgR is predictive of the effect of
           exemestane on PFS;

        2. to test whether the addition of exemestane to the standard front line treatment can
           prolong Overall Survival (OS);

        3. to evaluate objective response rate Overall Response Rate (ORR) of experimental
           treatment compared with the standard one;

        4. to assess whether the effect of exemestane is affected by the proliferative index Ki67;

        5. to evaluate the effect of exemestane on Quality of Life (QoL);

        6. to evaluate the compliance to the study treatment;

        7. to evaluate the safety profile of the experimental treatment compared with the standard
           one.

      Study design: a total of 468 subjects (234 per Arm) will be randomized in a 1:1 ratio to
      receive either standard chemotherapy treatment plus exemestane (Experimental arm) or standard
      chemotherapy plus placebo (Control arm). Exemestane/placebo will be self-administered as a
      single oral tablet of 25 mg/day until disease progression, unacceptable toxicity or
      physician/patient decision to withdraw, whichever comes first. Radiological disease
      assessments and CA125 will be performed at baseline and every 4 months from randomization,
      until end of study or disease progression whichever comes first. Safety assessments will be
      performed at each cycle during standard chemotherapy treatment, then at each study visit, up
      to 30 days after the last Experimental Treatment administration.Quality of Life will be
      assessed by a menopause-specific questionnaire, administered to patients at baseline (T0), at
      12 months (T1) and at disease progression (T2). For patients who have signed the specific
      informed consent, tissues and blood samples will be collected.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Progression free survival (PFS)
time frame: Up to 20 months
description: PFS id defined for each patient as the time from the date of randomization to the date of local or regional relapse, distant metastasis, second primary malignancy or death from any cause, whichever comes first. Patients not recurred, progressed or died while on study or lost to follow-up will be censored at their last disease assessment date.
measure: Overall survival (OS)
time frame: Up to 20 months
description: OS is defined for each patient as the time from the date of randomization to the date of death from any cause. Patients not reported as having died at the end of the study will be censored at the date they were last known to be alive.
measure: Objective Response Rate (ORR)
time frame: a CT-scan will be performed every 4 months. Up to 20 months from last patients randomized
description: ORR is defined as the number of patients who will experience a complete or partial response divided by the number of patients randomized with at least one target lesion at baseline. Each patient will be assigned the best response ever recorded during the trial
measure: Quality of Life: Menopause Quality of Life (MENQoL) questionnaire
time frame: Up to 20 months
description: The effect of study treatment will be assessed based on the MENQOL intervention questionnaire based on 29 items divided in four domains (vasomotor, physical, psychosocial and sexual), each scored from 1 to 8 (1 means no symptom, 2 presence of the symptoms but not bothersome, 3-8 an increasing grade of discomfort). Mean changes from the baseline domain scores between treatment arms will be evaluated.
measure: Compliance - Number of administered cycles
time frame: Up to 20 months
description: Number of administered cycles
measure: Compliance - Reasons for discontinuation and treatment modification
time frame: Up to 20 months
description: Number of patients for each reasons
measure: Compliance - Dose intensity
time frame: Up to 20 months
description: Number of tablets taken (i.e., number of tablets given-number of tablets returned)/number of tablets that should have been taken during the treatment period.
measure: Safety (Adverse Events)
time frame: Up to 20 months
description: Maximum toxicity grade experienced by each patient for each toxicity, proportion of patients experiencing grade 3-4 toxicity for each toxicity, type, frequency and nature of serious adverse events (SAEs).
Proportion of patients with at least one SAE.
Proportion of patients with at least one serious adverse drug reaction (SADR).
measure: Circulating and tissue biomarkers
time frame: Up to 20 months
description: To collect and store blood and tissue samples to create a bio-bank for the assessment of circulating and tissue biomarkers with potentially prognostic/predictive value, including the androgen receptor (AR) expression and the generation of a somatic genomic and transcriptomic atlas of epithelial ovarian cancers, to map the different molecular vulnerabilities lagging behind the single definition of each histological subtype. Data generated will allow to select molecular biomarkers with prognostic/predictive relevance, to have information of patients risk of relapse or to guide novel treatment approaches.
These biomarker endpoints will be considered in a second phase of the study, if additional funds are available to perform the analyses.
arm group label: Exemestane
arm group type: Experimental
description: Standard chemotherapy: paclitaxel 175 mg/m2 + carboplatin AUC 5, on day 1 every 21 days ± bevacizumab 15mg/kg, on day 1 every 21 days. Chemotherapy will be administered for 6 cycles; Bevacizumab will be administered as up to a maximum of 22 cycles. Patients unfit for standard treatment can receive a weekly schedule of treatment or monotherapy with carboplatin alone. Neoadjuvant chemotherapy is allowed in patients unfit for primary elective surgery.
+
Exemestane: single oral tablet of 25 mg/day until disease progression, unacceptable toxicity or physician/patient decision to withdraw, whichever comes first.
arm group label: Placebo
arm group type: Placebo Comparator
description: Standard chemotherapy : paclitaxel 175 mg/m2 + carboplatin AUC 5, on day 1 every 21 days ± bevacizumab 15mg/kg, on day 1 every 21 days. Chemotherapy will be administered for 6 cycles; Bevacizumab will be administered as up to a maximum of 22 cycles. Patients unfit for standard treatment can receive a weekly schedule of treatment or monotherapy with carboplatin alone. Neoadjuvant chemotherapy is allowed in patients unfit for primary elective surgery.
+
Placebo: single oral tablet until disease progression, unacceptable toxicity or physician/patient decision to withdraw, whichever comes first.
intervention type: Drug
intervention name: Exemestane
description: Exemestane in addition to standard therapy, in Experimental arm.
arm group label: Exemestane
other name: Mestane
intervention type: Other
intervention name: Placebo oral tablet
description: Placebo in addition to standard therapy, in Control arm.
arm group label: Placebo
criteria: 
gender: Female
gender based: Yes
gender description: Female patients
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Andrea DeCensi
role: Principal Investigator
affiliation: E.O. Ospedali Galliera Genova
last name: Alessandra Argusti
phone: 00390105634188
email: alessandra.argusti@galliera.it
last name: Silvia Caviglia
phone: 00390105634234
email: silvia.caviglia@galliera.it
facility: 
status: Not yet recruiting
contact: 
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status: Not yet recruiting
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status: Not yet recruiting
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status: Not yet recruiting
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status: Not yet recruiting
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status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
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status: Not yet recruiting
contact: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: Ente Ospedaliero Ospedali Galliera
investigator full name: Andrea DeCensi
investigator title: Principal Investigator
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Exemestane
sharing ipd: Yes
ipd description: Individual participant data that underlie the results reported in the primary publication of the trial will be shared (text, tables, figures, and appendices), after deidentification.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Data will be shared 3 months following the publication of the article and they will remain available for 36 months.
ipd access criteria: the investigators who would like to use the data have to prepare a proposal that needs to be approved the Steering committee. The aim of the access to study data needs to be specified in the proposal. Proposals should be sent to the Principal investigator (andrea.decensi@galliera.it). To gain access, data requestors will need to sign a data access agreement.