<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/NCT03809988</url>
  </required_header>
  <id_info>
    <org_study_id>MedOPP068</org_study_id>
    <secondary_id>2017-002781-48</secondary_id>
    <nct_id>NCT03809988</nct_id>
  </id_info>
  <brief_title>PALbociclib Rechallenge in horMone Receptor-posItive/HER2- Negative Advanced Breast Cancer (PALMIRA)</brief_title>
  <acronym>PALMIRA</acronym>
  <official_title>International,Multicenter,Randomized,Open-label, Phase II to Evaluate the Efficacy and Safety of Continuation of Palbociclib+2nd Line Endocrine Therapy in HR+/HER2- ABC Patients Who Had Clinical Benefit During 1st Line Palbociclib.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>MedSIR</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>MedSIR</source>
  <oversight_info>
    <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>
      Hormone Receptor (HR)-positive/Human Epidermal Growth Factor Receptor 2 (HER2)-negative&#xD;
      advanced breast cancer (ABC)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Pre- and post-menopausal women age ≥ 18 years with HR-positive and HER2-negative with ABC&#xD;
      that had previously received first-line endocrine therapy in combination with palbociclib and&#xD;
      had achieved clinical benefit during palbociclib-based treatment. Patients relapsing on a&#xD;
      palbociclib-based regimen in the adjuvant setting are also eligible. Patients are not&#xD;
      eligible if they are candidates for a local treatment with a curative intention. Evidence of&#xD;
      either measurable and biopsiable metastatic disease (as for Response Evaluation Criteria In&#xD;
      Solid Tumors (RECIST v.1.1)) or non-measurable disease with bone lesion is required.&#xD;
      Pre-menopausal women must be under treatment with luteinizing hormone-releasing hormone&#xD;
      (LHRH) analogues.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 5, 2019</start_date>
  <completion_date type="Actual">November 30, 2022</completion_date>
  <primary_completion_date type="Actual">November 30, 2022</primary_completion_date>
  <phase>Phase 2</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>Randomized 2:1</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>PFS (Progression-free survival)</measure>
    <time_frame>Baseline up to 29 months</time_frame>
    <description>From a clinical point of view, the primary endpoint for this study is the PFS (progression-free survival) - defined as the period of time from randomization until objective tumor progression or death - assessed by RECIST criteria v.1.1, of continuation of palbociclib treatment combined with second-line endocrine therapy (letrozole or fulvestrant) versus endocrine therapy in pre- and post- menopausal women with HR-positive/HER2-negative ABC.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety AEs</measure>
    <time_frame>Baseline up to 29 months</time_frame>
    <description>Patient safety and adverse events (AEs) will be evaluated using the NCI-CTCAE v.5.0. Grade 3 and 4 AEs and serious adverse events (SAEs) will be assessed to determine the safety and tolerability of the different treatment arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy (ORR)</measure>
    <time_frame>Baseline up to 29 months</time_frame>
    <description>To compare the objective response rate (ORR), the duration of response (DoR), the time to response (TTR), the clinical benefit rate (CBR), the time to progression (TTP), and the overall survival (OS) of palbociclib plus second-line endocrine therapy (letrozole or fulvestrant) versus endocrine therapy alone</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy (Quality of Life)</measure>
    <time_frame>Baseline up to 42 months</time_frame>
    <description>To compare the patient reported global Quality of Life (QOL), functioning and symptoms of palbociclib plus second-line endocrine therapy (letrozole or fulvestrant) versus endocrine therapy alone.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy of subgroup analysis</measure>
    <time_frame>Baseline up to 42 months</time_frame>
    <description>To perform subgroup analysis for primary and secondary endpoints in stratified groups of patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare efficacy</measure>
    <time_frame>Baseline up to 42 months</time_frame>
    <description>To compare the time to first chemotherapy of palbociclib plus second-line endocrine therapy (letrozole or fulvestrant) versus endocrine therapy alone.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory objectives (molecular markers)</measure>
    <time_frame>Baseline up to 42 months</time_frame>
    <description>To explore potential molecular markers of sensitivity and/or resistance for the combination and endocrine therapy alone, according to, but not limited to, the results obtained from the BioPER trial (NCT03184090).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory objectives (intrinsic molecular subtypes)</measure>
    <time_frame>Baseline up to 42 months</time_frame>
    <description>To explore correlations between the intrinsic molecular subtypes and efficacy/safety findings in patients with HR-positive/HER2- negative ABC.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">198</enrollment>
  <condition>Breast Cancer</condition>
  <condition>Advanced Breast Cancer</condition>
  <condition>Hormone Receptor Positive Tumor</condition>
  <condition>Human Epidermal Growth Factor 2 Negative Carcinoma of Breast</condition>
  <arm_group>
    <arm_group_label>Interventional Arm (Arm A)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive palbociclib capsules orally once daily (QD) (at 100mg or 125mg depending on previous treatment dose) for 21 days every four weeks in combination with endocrine therapy (letrozole or fulvestrant).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Arm (Arm B)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will receive endocrine therapy (letrozole or fulvestrant).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Palbociclib</intervention_name>
    <description>Palbociclib capsules orally once daily (QD) (at 100mg or 125mg depending on previous treatment dose) for 21 days every four weeks</description>
    <arm_group_label>Interventional Arm (Arm A)</arm_group_label>
    <other_name>IBRANCE</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Endocrine therapy</intervention_name>
    <description>Endocrine therapy alone (letrozole or fulvestrant)</description>
    <arm_group_label>Control Arm (Arm B)</arm_group_label>
    <arm_group_label>Interventional Arm (Arm A)</arm_group_label>
    <other_name>letrozole</other_name>
    <other_name>fulvestrant</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Female patients over 18 years of age.&#xD;
&#xD;
          2. Pre-menopausal women provided they are being treated with a LHRH analogue for at least&#xD;
             28 days (if shorter, post-menopausal levels of serum estradiol/Follicle-stimulating&#xD;
             hormone (FSH) must be confirmed analytically) prior to study entry or post- menopausal&#xD;
             women as defined by any of the following criteria:&#xD;
&#xD;
               1. Age ≥60 years;&#xD;
&#xD;
               2. Age &lt;60 years and cessation of regular menses for at least 12 consecutive months&#xD;
                  with no alternative pathological or physiological cause; and serum estradiol&#xD;
                  and/or FSH level within the laboratory's reference range for postmenopausal&#xD;
                  females;&#xD;
&#xD;
               3. Documented bilateral oophorectomy.&#xD;
&#xD;
          3. Eastern Cooperative Oncology Group (ECOG) performance status lower or equal to 1.&#xD;
&#xD;
          4. Life expectancy greater or equal to 12 weeks.&#xD;
&#xD;
          5. Histologically proven diagnosed of ABC not amenable to curative treatment.&#xD;
&#xD;
          6. Documented recurrent ER-positive and/or progesterone receptor (PgR)-positive (with ≥1%&#xD;
             positive stained cells (according to NCCN National Comprehensive Cancer Network and&#xD;
             ASCO American Society of Clinical Oncology guidelines) and HER2-negative (0-1+ by&#xD;
             immunohistochemistry (IHC) or 2+ and negative by in situ hybridization (ISH) test)&#xD;
             breast cancer in the advanced setting.&#xD;
&#xD;
          7. Radiological or clinical evidence of disease progression on first- line combination of&#xD;
             palbociclib plus endocrine therapy (aromatase inhibitor (AI) or fulvestrant). Patients&#xD;
             previously treated with the combination of palbociclib and tamoxifen will be excluded.&#xD;
&#xD;
          8. Patients have achieved clinical benefit criteria to a first-line palbociclib-based&#xD;
             endocrine regimen (defined as at least stable disease ≥ 24 weeks or partial or&#xD;
             complete response confirmed or unconfirmed).&#xD;
&#xD;
          9. Patients must have been treated with a stable minimum dose of 75 mg palbociclib during&#xD;
             the last 2 cycles of the prior palbociclib-based regimen.&#xD;
&#xD;
         10. Last dose of palbociclib administered not later than 8 weeks and not earlier than 7&#xD;
             days from study entry, with the exception of patients relapsing on a palbociclib-based&#xD;
             regimen in the adjuvant setting.&#xD;
&#xD;
         11. Patients should not have been treated in the advanced setting with at least one of&#xD;
             these endocrine therapy options: either fulvestrant or AI.&#xD;
&#xD;
         12. Patients must have measurable disease or evaluable disease according to RECIST&#xD;
             criteria v.1.1. Patients with only bone lesions are eligible.&#xD;
&#xD;
         13. Willingness and ability to provide tumor biopsy (if feasible) both at the time of the&#xD;
             inclusion and after disease progression in order to perform exploratory studies. If&#xD;
             not feasible, patient eligibility should be evaluated by a Sponsor's qualified&#xD;
             designee.&#xD;
&#xD;
         14. Patients agree to collection of blood samples (liquid biopsy) at the time of&#xD;
             inclusion, after 2 weeks of treatment, and upon progression or study termination.&#xD;
&#xD;
         15. Adequate organ function: (Hematological, hepatic and renal)&#xD;
&#xD;
         16. Patients who are willing and able to comply with scheduled visits, treatment plan,&#xD;
             laboratory tests, and other study procedures.&#xD;
&#xD;
         17. Patients have been informed about the nature of study, and have agreed to participate&#xD;
             in the study, and signed the informed consent form prior to participation in any&#xD;
             study-related activities.&#xD;
&#xD;
         18. Resolution of all acute toxic effects of prior anti-cancer therapy to grade 1&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. HR or HER2 unknown disease.&#xD;
&#xD;
          2. HER2-positive disease based on local laboratory results (performed by IHC / ISH test).&#xD;
&#xD;
          3. Locally ABC candidate for curative treatment.&#xD;
&#xD;
          4. Formal contraindication to endocrine therapy defined as visceral crisis and rapidly or&#xD;
             symptomatic progressive visceral disease.&#xD;
&#xD;
          5. Prior therapy with any other CDK4/6 inhibitor different from palbociclib.&#xD;
&#xD;
          6. Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases,&#xD;
             carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms,&#xD;
             cerebral edema, and/or progressive growth. Patients with a history of CNS metastases&#xD;
             or cord compression are eligible if they have been definitively treated and are&#xD;
             clinically stable off anticonvulsants and steroids for at least 4 weeks before&#xD;
             randomization.&#xD;
&#xD;
          7. Patients are currently receiving food or drugs known to be strong inducers or&#xD;
             inhibitors of CYP3A4.&#xD;
&#xD;
          8. Current or prior malignancy which could affect compliance with the protocol or&#xD;
             interpretation of results. Patients with curatively- treated non-melanoma skin cancer,&#xD;
             non-muscle-invasive bladder cancer, or carcinoma in situ, among others, are generally&#xD;
             eligible.&#xD;
&#xD;
          9. No other systemic therapy for metastatic disease including chemotherapy,&#xD;
             immunotherapy, targeted therapy (small molecules/ monoclonal antibodies), or endocrine&#xD;
             therapy excluding first-line palbociclib-based regimen.&#xD;
&#xD;
         10. Major surgery (defined as requiring general anesthesia) or significant traumatic&#xD;
             injury within 2 weeks of start of study drug, or patients who have not recovered from&#xD;
             the side effects of any major surgery, or patients who may require major surgery&#xD;
             during the study.&#xD;
&#xD;
         11. Radiotherapy or limited-field palliative radiotherapy within 7 days prior to study&#xD;
             enrolment, or patients who have not recovered from radiotherapy-related toxicities to&#xD;
             baseline or grade ≤ 1 and/or from whom ≥ 25% of the bone marrow has been previously&#xD;
             irradiated.&#xD;
&#xD;
         12. Use of concurrent investigational agents or other concomitant anticancer therapies.&#xD;
&#xD;
         13. Active bleeding diathesis, previous history of bleeding diathesis, or chronic&#xD;
             anti-coagulation treatment (the use of low molecular weight heparin is allowed as soon&#xD;
             as it is used as prophylaxis intention).&#xD;
&#xD;
         14. Serious concomitant systemic disorder (e.g., active infection including HIV, or&#xD;
             cardiac disease) incompatible with the study (at the discretion of investigator).&#xD;
&#xD;
         15. Unable to swallow capsules or tablets.&#xD;
&#xD;
         16. History of malabsorption syndrome or other condition that would interfere with enteral&#xD;
             absorption.&#xD;
&#xD;
         17. Any of the following within 6 months of randomization:&#xD;
&#xD;
             myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of&#xD;
             NCI-CTCAE v.5.0 grade ≥2, coronary/peripheral artery bypass graft, symptomatic&#xD;
             congestive heart failure, cerebrovascular accident including transient ischemic&#xD;
             attack, or symptomatic pulmonary embolism.&#xD;
&#xD;
         18. Uncontrolled electrolyte disorders of NCI-CTCAE v.5.0 grade ≥ 2.&#xD;
&#xD;
         19. Known hypersensitivity to palbociclib or any of its excipients.&#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_official>
    <last_name>José Perez</last_name>
    <role>Principal Investigator</role>
    <affiliation>MedSIR</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hôpital Jean Minjoz</name>
      <address>
        <city>Besançon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Polyclinique Bordeaux Nord Aquitaine</name>
      <address>
        <city>Bordeaux</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Georges François Leclerc</name>
      <address>
        <city>Dijon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHD Vendee</name>
      <address>
        <city>La Roche-sur-Yon</city>
        <zip>85925</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Europeen Georges Pompidou</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Tenon AP-HP</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Paul Strauss</name>
      <address>
        <city>Strasbourg</city>
        <zip>67000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Dresden-GYN</name>
      <address>
        <city>Dresden</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kliniken Essen Mitte</name>
      <address>
        <city>Essen</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Essen Frauenklinik</name>
      <address>
        <city>Essen</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AGAPLESION Markus Krankenhaus</name>
      <address>
        <city>Frankfurt</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Technical University Munich</name>
      <address>
        <city>Munich</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UKM Brustzentrum</name>
      <address>
        <city>Münster</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum Ernst von Bergmann</name>
      <address>
        <city>Potsdam</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum Mutterhaus der Borromäerinnen Trier</name>
      <address>
        <city>Trier</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Civili Brescia</name>
      <address>
        <city>Brescia</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Europeo di Oncologia</name>
      <address>
        <city>Milano</city>
        <zip>20141</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncologia Medica Ospedale di Prato</name>
      <address>
        <city>Prato</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinico Universitario Campus Bio-medico</name>
      <address>
        <city>Roma</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Onkološki Inštitut Ljubljana</name>
      <address>
        <city>Ljubljana</city>
        <country>Slovenia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Univerzitetni klinicni center Maribor Oddelek za onkologijo</name>
      <address>
        <city>Maribor</city>
        <country>Slovenia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ICO Badalona</name>
      <address>
        <city>Badalona</city>
        <state>Barcelona</state>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Provincial de Castellón</name>
      <address>
        <city>Castello</city>
        <state>Castelló</state>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Consorci Sanitari de Terrassa</name>
      <address>
        <city>Terrassa</city>
        <state>Terrasa</state>
        <zip>08191</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Oncológico de Galicia</name>
      <address>
        <city>A Coruña</city>
        <zip>15009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Català d'Oncologia Bellvitge</name>
      <address>
        <city>Barcelona</city>
        <zip>08908</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>H. Vall Hebrón</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital del Mar</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Basurto</name>
      <address>
        <city>Bilbao</city>
        <zip>48013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital San Pedro de Alcantara</name>
      <address>
        <city>Cáceres</city>
        <zip>10003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Català d'Oncologia</name>
      <address>
        <city>Girona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Arnau de Vilanova</name>
      <address>
        <city>Lleida</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico San Carlos</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Sanchinarro</name>
      <address>
        <city>Madrid</city>
        <zip>28050</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital La Paz</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Regional Universitario de Malaga</name>
      <address>
        <city>Málaga</city>
        <zip>29010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Son Espases</name>
      <address>
        <city>Palma De Mallorca</city>
        <zip>07120</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Sant Joan</name>
      <address>
        <city>Reus</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen de la Macarena</name>
      <address>
        <city>Sevilla</city>
        <zip>41009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen del Rocío</name>
      <address>
        <city>Sevilla</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Valenciano de Oncología IVO</name>
      <address>
        <city>Valencia</city>
        <zip>46009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitari de Valencia</name>
      <address>
        <city>Valencia</city>
        <zip>46014</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Arnau de Vilanova de Valencia</name>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari i Politecnic La Fe</name>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Álvaro Cunqueiro</name>
      <address>
        <city>Vigo</city>
        <zip>36312</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Lozano Blesa</name>
      <address>
        <city>Zaragoza</city>
        <zip>50009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Miguel Servet</name>
      <address>
        <city>Zaragoza</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Darent Valley Hospital by Dartford and Gravesham NHS Trust</name>
      <address>
        <city>Dartford</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beatson West of Scotland Cancer Center</name>
      <address>
        <city>Glasgow</city>
        <zip>G12 0YN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Barts Cancer Institute</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kent Oncology Department</name>
      <address>
        <city>Maidstone</city>
        <zip>ME16 9QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Abertawe Bro Morgannwg University Local Health Board, Singleton Hospital</name>
      <address>
        <city>Swansea</city>
        <zip>SA127BR</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Cornwall Hospital NHS Trust</name>
      <address>
        <city>Truro</city>
        <zip>TR1 3LQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Slovenia</country>
    <country>Spain</country>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>January 15, 2019</study_first_submitted>
  <study_first_submitted_qc>January 16, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 18, 2019</study_first_posted>
  <last_update_submitted>September 6, 2023</last_update_submitted>
  <last_update_submitted_qc>September 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HR</keyword>
  <keyword>breast cancer</keyword>
  <keyword>ABC</keyword>
  <keyword>progesterone receptor</keyword>
  <keyword>HER2</keyword>
  <keyword>advanced</keyword>
  <keyword>estrogen receptor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Letrozole</mesh_term>
    <mesh_term>Fulvestrant</mesh_term>
    <mesh_term>Palbociclib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Study Leaflet V2_20190115 with study design, primary objetive, inclusion criteria and exclusion criteria</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_time_frame>During recruitment period</ipd_time_frame>
    <ipd_access_criteria>Oncology department</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/NCT03809988
org study id: MedOPP068
secondary id: 2017-002781-48
nct id: NCT03809988
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
is us export: No
Hormone Receptor (HR)-positive/Human Epidermal Growth Factor Receptor 2 (HER2)-negative
      advanced breast cancer (ABC)
Pre- and post-menopausal women age ≥ 18 years with HR-positive and HER2-negative with ABC
      that had previously received first-line endocrine therapy in combination with palbociclib and
      had achieved clinical benefit during palbociclib-based treatment. Patients relapsing on a
      palbociclib-based regimen in the adjuvant setting are also eligible. Patients are not
      eligible if they are candidates for a local treatment with a curative intention. Evidence of
      either measurable and biopsiable metastatic disease (as for Response Evaluation Criteria In
      Solid Tumors (RECIST v.1.1)) or non-measurable disease with bone lesion is required.
      Pre-menopausal women must be under treatment with luteinizing hormone-releasing hormone
      (LHRH) analogues.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized 2:1
primary purpose: Treatment
masking: None (Open Label)
measure: PFS (Progression-free survival)
time frame: Baseline up to 29 months
description: From a clinical point of view, the primary endpoint for this study is the PFS (progression-free survival) - defined as the period of time from randomization until objective tumor progression or death - assessed by RECIST criteria v.1.1, of continuation of palbociclib treatment combined with second-line endocrine therapy (letrozole or fulvestrant) versus endocrine therapy in pre- and post- menopausal women with HR-positive/HER2-negative ABC.
measure: Safety AEs
time frame: Baseline up to 29 months
description: Patient safety and adverse events (AEs) will be evaluated using the NCI-CTCAE v.5.0. Grade 3 and 4 AEs and serious adverse events (SAEs) will be assessed to determine the safety and tolerability of the different treatment arms.
measure: Efficacy (ORR)
time frame: Baseline up to 29 months
description: To compare the objective response rate (ORR), the duration of response (DoR), the time to response (TTR), the clinical benefit rate (CBR), the time to progression (TTP), and the overall survival (OS) of palbociclib plus second-line endocrine therapy (letrozole or fulvestrant) versus endocrine therapy alone
measure: Efficacy (Quality of Life)
time frame: Baseline up to 42 months
description: To compare the patient reported global Quality of Life (QOL), functioning and symptoms of palbociclib plus second-line endocrine therapy (letrozole or fulvestrant) versus endocrine therapy alone.
measure: Efficacy of subgroup analysis
time frame: Baseline up to 42 months
description: To perform subgroup analysis for primary and secondary endpoints in stratified groups of patients.
measure: Compare efficacy
time frame: Baseline up to 42 months
description: To compare the time to first chemotherapy of palbociclib plus second-line endocrine therapy (letrozole or fulvestrant) versus endocrine therapy alone.
measure: Exploratory objectives (molecular markers)
time frame: Baseline up to 42 months
description: To explore potential molecular markers of sensitivity and/or resistance for the combination and endocrine therapy alone, according to, but not limited to, the results obtained from the BioPER trial (NCT03184090).
measure: Exploratory objectives (intrinsic molecular subtypes)
time frame: Baseline up to 42 months
description: To explore correlations between the intrinsic molecular subtypes and efficacy/safety findings in patients with HR-positive/HER2- negative ABC.
arm group label: Interventional Arm (Arm A)
arm group type: Experimental
description: Patients will receive palbociclib capsules orally once daily (QD) (at 100mg or 125mg depending on previous treatment dose) for 21 days every four weeks in combination with endocrine therapy (letrozole or fulvestrant).
arm group label: Control Arm (Arm B)
arm group type: Active Comparator
description: Patients will receive endocrine therapy (letrozole or fulvestrant).
intervention type: Drug
intervention name: Palbociclib
description: Palbociclib capsules orally once daily (QD) (at 100mg or 125mg depending on previous treatment dose) for 21 days every four weeks
arm group label: Interventional Arm (Arm A)
other name: IBRANCE
intervention type: Drug
intervention name: Endocrine therapy
description: Endocrine therapy alone (letrozole or fulvestrant)
arm group label: Control Arm (Arm B)
arm group label: Interventional Arm (Arm A)
other name: letrozole
other name: fulvestrant
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: José Perez
role: Principal Investigator
affiliation: MedSIR
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country: France
country: Germany
country: Italy
country: Slovenia
country: Spain
country: United Kingdom
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Letrozole
mesh term: Fulvestrant
mesh term: Palbociclib
sharing ipd: Yes
ipd description: Study Leaflet V2_20190115 with study design, primary objetive, inclusion criteria and exclusion criteria
ipd info type: Study Protocol
ipd time frame: During recruitment period
ipd access criteria: Oncology department