<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/NCT03820830</url>
  </required_header>
  <id_info>
    <org_study_id>IBCSG 59-19</org_study_id>
    <secondary_id>2018-003553-19</secondary_id>
    <secondary_id>BIG 18-02</secondary_id>
    <secondary_id>WI239003</secondary_id>
    <nct_id>NCT03820830</nct_id>
  </id_info>
  <brief_title>Palbociclib for HR Positive / HER2-negative Isolated Locoregional Recurrence of Breast Cancer</brief_title>
  <acronym>POLAR</acronym>
  <official_title>A Phase III Open-label, Multicenter, Randomized Trial of Adjuvant Palbociclib in Combination With Endocrine Therapy Versus Endocrine Therapy Alone for Patients With Hormone Receptor Positive / HER2-negative Resected Isolated Locoregional Recurrence of Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ETOP IBCSG Partners Foundation</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>ETOP IBCSG Partners Foundation</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>
      POLAR is a phase III clinical trial, which will test the safety and efficacy of an&#xD;
      investigational combination of drugs to learn whether the combination of drugs works for a&#xD;
      specific cancer. Palbociclib (Ibrance®) is the name of the investigational agent, which is&#xD;
      assessed together with standard anti-hormone therapy in this study. Palbociclib is used to&#xD;
      treat patients with hormone receptor-positive / HER2-negative breast cancer which has spread&#xD;
      beyond the original tumor and/or to other organs.&#xD;
&#xD;
      During this study, anti-hormone therapy will consist of either a selective estrogen receptor&#xD;
      modulator (such as tamoxifen) or an aromatase inhibitor (anastrozole, letrozole, exemestane)&#xD;
      or fulvestrant (Faslodex®). Premenopausal women and men may also receive a drug called an&#xD;
      LHRH (luteinizing hormone-releasing hormone) agonist by injection.&#xD;
&#xD;
      It is standard of care for people with hormone receptor positive breast cancer to take&#xD;
      anti-hormone therapy. The study doctor will determine the type of standard anti-hormone&#xD;
      therapy that will be given during this trial.&#xD;
&#xD;
      The purpose of the POLAR study is to compare the effect of using 3 years of palbociclib in&#xD;
      combination with standard anti-hormone therapy with standard anti-hormone therapy alone and&#xD;
      to evaluate the time until the breast cancer returns, if it does return.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Local or regional recurrence of breast cancer after mastectomy or lumpectomy indicates a poor&#xD;
      prognosis, and accompanies or precedes distant metastasis in a high proportion of patients.&#xD;
      Patients with isolated locoregional recurrences (ILRR), without evidence of distant&#xD;
      metastasis hold a substantial risk of developing subsequent distant metastasis, with 5-year&#xD;
      survival probabilities ranging between 45% and 80% after locoregional recurrence. These&#xD;
      outcomes show the powerful negative prognostic importance of ILRR events and the need for&#xD;
      treatments beyond surgical removal of the ILRR.&#xD;
&#xD;
      Adjuvant chemotherapy and endocrine therapies reduce the risk of relapse and death in&#xD;
      patients with primary breast cancer. However, few data are available to inform the&#xD;
      recommendation of systemic treatment for locoregional recurrence.&#xD;
&#xD;
      The International Breast Cancer Studies Group carried out the CALOR trial, Chemotherapy as&#xD;
      Adjuvant for Locally Recurrent breast cancer (IBCSG 27-02 / BIG 1-02 / NSABP B-37), in&#xD;
      collaboration with the Breast International Group (BIG) and the National Surgical Adjuvant&#xD;
      Breast and Bowel Project (NSABP), to establish whether chemotherapy improves the outcome of&#xD;
      patients with ILRR. An updated, final analysis of CALOR after median follow-up of about 9&#xD;
      years was published in the Journal of Clinical Oncology in April 2018, which confirmed&#xD;
      chemotherapy benefitted patients with resected ER-negative ILRR and did not support the use&#xD;
      of chemotherapy for ER-positive ILRR.&#xD;
&#xD;
      CALOR results strongly suggest that tailoring treatment according to the disease&#xD;
      characteristics of the recurrent lesion, in this case ILRR, provides a better indication of&#xD;
      the possible responsiveness to treatment than relying on the characteristics of the primary&#xD;
      tumor.&#xD;
&#xD;
      Palbociclib has been granted FDA approval in the U.S. for the treatment of&#xD;
      HR-positive/HER2-negative advanced breast cancer in combination with the hormonal treatments&#xD;
      letrozole and fulvestrant given the unprecedented results in terms of efficacy of two pivotal&#xD;
      clinical trials (PALOMA-2 and PALOMA-3). Palbociclib and other CDK4/6 inhibitors have also&#xD;
      shown a good toxicity profile and therefore are ideal candidates for combination with&#xD;
      hormonal therapy. CDK4/6 pathway activation is a well-known mechanism of resistance to&#xD;
      endocrine therapy, indeed CDK4/6 inhibitors have shown activity in cellular models of&#xD;
      acquired resistance to endocrine therapies.&#xD;
&#xD;
      The reason for prolonged duration of palbociclib in the adjuvant setting (2 years) comes from&#xD;
      the evidence of preclinical studies where cell senescence was investigated as an appealing&#xD;
      mechanism of cell death and was indeed observed in vitro after exposure of breast cancer&#xD;
      cells and tumors to a combination of endocrine therapy and palbociclib. It is therefore&#xD;
      hypothesized that the longer patients receive combined treatment with palbociclib and an&#xD;
      antiestrogen, the more likely they may derive prolonged clinical benefit.&#xD;
&#xD;
      Based on the results of the CALOR trial and on strong evidence of activity of the combination&#xD;
      of CDK4/6 inhibitors and endocrine therapy, the hypothesis of the POLAR trial is that the&#xD;
      CDK4/6 inhibitor palbociclib in combination with endocrine therapy may be active as adjuvant&#xD;
      therapy in patients with HR-positive/HER2-negative resected isolated locoregional recurrence&#xD;
      of breast cancer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 27, 2019</start_date>
  <completion_date type="Anticipated">November 1, 2026</completion_date>
  <primary_completion_date type="Anticipated">July 1, 2024</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Duration of invasive disease free survival of all randomized participants.</measure>
    <time_frame>Assessed from the date treatment starts until the date of first documented invasive local, regional or distant recurrence, a second invasive cancer or death, or until approximately 4 years after treatment stops.</time_frame>
    <description>Defined as the time from randomization until first appearance of invasive local, regional or distant recurrence (including invasive ipsilateral breast tumour recurrence), invasive contralateral breast cancer, a second (non-breast) invasive cancer, or death from any cause. The sites of first invasive disease events will be compared between treatment groups using a stratified log-rank test and will be tabulated.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment related adverse events.</measure>
    <time_frame>Adverse events will be collected from the date consent is signed, and during treatment until 30-60 days after treatment stops.</time_frame>
    <description>Adverse events, defined as any untoward medical occurrence, will be collected using CTCAE v5. All grades for targeted adverse events will be collected and all grades ≥3 for non-targeted adverse events. The maximum grade of each targeted adverse event during the protocol treatment phase will be determined, the frequencies summarized and tabulated according to grade and treatment assignment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of breast cancer free interval of all randomized participants.</measure>
    <time_frame>Assessed from the date of randomization until the date of first documented breast cancer recurrence, or until approximately 4 years after treatment stops.</time_frame>
    <description>Defined as the time from randomization until the date of first documented appearance of invasive local, regional or distant recurrence (including ipsilateral tumour recurrence), or invasive contralateral breast cancer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of distant recurrence free interval of all randomized participants.</measure>
    <time_frame>Assessed from the date of randomization until the date of first documented distant disease progression, or until approximately 4 years after treatment stops.</time_frame>
    <description>Defined as the time from randomization until the date of first documented distant recurrence of breast cancer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of overall survival of all randomized participants.</measure>
    <time_frame>Assessed from the date of randomization until approximately 4 years after treatment stops, or until the date of death from any cause.</time_frame>
    <description>Defined as the time from randomization until death from any cause.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">400</enrollment>
  <condition>Breast Cancer Recurrent</condition>
  <arm_group>
    <arm_group_label>Palbociclib plus standard endocrine therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Palbociclib 125 mg/day tablet taken orally for 21 days, followed by 7 days rest for 3 years from randomization, plus standard endocrine therapy for at least 3 years from randomization.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard endocrine therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Aromatase inhibitor (anastrozole or exemestane or letrozole) oral daily tablet, or Selective Estrogen Receptor Modulator (SERM) such as tamoxifen oral daily tablet or fulvestrant (Faslodex) injection once every 2 weeks for 3 doses then every month. Premenopausal women and men may also receive an LHRH (luteinizing hormone-releasing hormone) agonist by injection. Standard endocrine therapy will be given for at least 3 years from randomization.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Palbociclib 125mg</intervention_name>
    <description>Palbociclib 125 mg oral tablet taken daily for 3 years from randomization</description>
    <arm_group_label>Palbociclib plus standard endocrine therapy</arm_group_label>
    <other_name>Ibrance</other_name>
    <other_name>PD-0332991</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard endocrine therapy</intervention_name>
    <description>Aromatase inhibitor (anastrozole or exemestane or letrozole) oral daily tablet, or Selective Estrogen Receptor Modulator (SERM) such as tamoxifen oral daily tablet or fulvestrant (Faslodex) injection once every 2 weeks for 3 doses then every month. Premenopausal women and men may also receive an LHRH (luteinizing hormone-releasing hormone) agonist by injection. Standard endocrine therapy will be given for at least 3 years from randomization.</description>
    <arm_group_label>Palbociclib plus standard endocrine therapy</arm_group_label>
    <arm_group_label>Standard endocrine therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed invasive breast cancer, defined as first proven ipsilateral&#xD;
             local and/or regional recurrence of a primary invasive breast cancer in at least one&#xD;
             of these sites:&#xD;
&#xD;
               -  breast;&#xD;
&#xD;
               -  the chest wall including mastectomy scar and/or skin;&#xD;
&#xD;
               -  axillary or internal mammary lymph nodes.&#xD;
&#xD;
          2. Completion of locoregional therapy:&#xD;
&#xD;
               -  completion of gross excision of recurrence within 6 months prior to&#xD;
                  randomization;&#xD;
&#xD;
               -  completion of radiotherapy (if given) more than 2 weeks prior to randomization&#xD;
&#xD;
          3. Negative or microscopically involved margins&#xD;
&#xD;
          4. Female or male aged 18 years or older&#xD;
&#xD;
          5. ECOG performance status 0 or 1&#xD;
&#xD;
          6. Recurrent tumor must be hormone receptor positive: ER+ and/or PgR+ ≥1% by IHC&#xD;
&#xD;
          7. Recurrent tumor must be HER2-negative (0, 1+, 2+ by IHC and/or ISH/FISH not&#xD;
             amplified).Tumor with HER2 status 2+ by IHC must also be negative (not amplified) by&#xD;
             ISH/FISH&#xD;
&#xD;
        8.-10. Normal hematological, renal, and liver function 11. The patient agrees to make tumor&#xD;
        (diagnostic core biopsy or surgical specimen of ipsilateral isolated locoregional&#xD;
        recurrence) available for submission for central pathology review 12. Patients must either&#xD;
        be planned to initiate, or have already started, endocrine therapy for ipsilateral isolated&#xD;
        locoregional recurrence 13.) Written Informed Consent prior to randomization&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Recurrence of any size with direct extension to the chest wall and/or to the skin&#xD;
             (ulceration or skin nodules) not surgically removable&#xD;
&#xD;
          2. Evidence of distant metastasis as based on conventional staging examinations&#xD;
             (physical, chest X-ray or CT, abdominal ultrasound or CT, bone scintigraphy or&#xD;
             FDG-PET-CT).&#xD;
&#xD;
          3. Bilateral synchronous or metachronous invasive breast cancer (in situ carcinoma of the&#xD;
             contralateral breast is allowed)&#xD;
&#xD;
          4. Inflammatory breast cancer&#xD;
&#xD;
          5. Patients with a history of malignancy, other than invasive breast cancer, with the&#xD;
             following exceptions:&#xD;
&#xD;
               -  Patients diagnosed, treated and disease-free for at least 5 years and deemed by&#xD;
                  the investigator to be at low risk for recurrence of that malignancy are&#xD;
                  eligible.&#xD;
&#xD;
               -  Patients with the following malignancies are eligible, even if diagnosed and&#xD;
                  treated within the past 5 years: ductal carcinoma in situ of the breast; cervical&#xD;
                  cancer in situ; thyroid cancer in situ; non-metastatic, non-melanomatous skin&#xD;
                  cancers.&#xD;
&#xD;
          6. Previous treatment with palbociclib or any other CDK 4/6 inhibitors&#xD;
&#xD;
          7. Previous or planned chemotherapy or planned radiotherapy for the ipsilateral isolated&#xD;
             locoregional recurrence (radiotherapy is allowed, but must be completed more than 2&#xD;
             weeks prior to randomization)&#xD;
&#xD;
          8. Concurrent disease or condition that would make the patient inappropriate for study&#xD;
             participation or any serious medical disorder that would interfere with the patient's&#xD;
             safety&#xD;
&#xD;
          9. Pregnant or lactating women; lactation has to stop before randomization&#xD;
&#xD;
         10. Patients with psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements&#xD;
&#xD;
         11. Contraindications or known hypersensitivity to the palbociclib or excipients&#xD;
&#xD;
         12. History of extensive disseminated/bilateral or known presence of interstitial fibrosis&#xD;
             or interstitial lung disease, including a history of pneumonitis, hypersensitivity&#xD;
             pneumonitis, interstitial pneumonia, obliterative bronchiolitis, and pulmonary&#xD;
             fibrosis. A history of prior radiation pneumonitis is not considered an exclusion&#xD;
             criterion.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Elisabetta Munzone, MD</last_name>
    <role>Study Chair</role>
    <affiliation>European Institute of Oncology</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Holly Shaw</last_name>
    <phone>+17168340900</phone>
    <email>ibcsg59_polar@fstrf.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Adriana Karausch</last_name>
    <email>ibcsg59_polar@fstrf.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Medizinische Universität Graz (MUG)</name>
      <address>
        <city>Graz</city>
        <country>Austria</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marija Balic, PD</last_name>
      <email>marija.balic@medunigraz.at</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Medizinische Universität Innsbruck - Univ.-Klinik f. Frauenheilkunde</name>
      <address>
        <city>Innsbruck</city>
        <country>Austria</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Daniel Egle, PD</last_name>
      <email>daniel.egle@tirol-kliniken.at</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Uniklinikum Salzburg</name>
      <address>
        <city>Salzburg</city>
        <country>Austria</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Richard Greil, Prof.</last_name>
      <email>r.greil@salk.at</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>MUW - Universitätsklinik für Innere Medizin</name>
      <address>
        <city>Vienna</city>
        <country>Austria</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rupert Bartsch, Prof.</last_name>
      <email>rupert.bartsch@meduniwien.ac.at</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Institut Sainte Catherine</name>
      <address>
        <city>Avignon</city>
        <zip>84918</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Julien Grenier, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Institut Bergonie</name>
      <address>
        <city>Bordeaux</city>
        <zip>33076</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Herve Bonnefoi, Prof.</last_name>
      <email>h.bonnefoi@bordeaux.unicancer.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Polyclinique Bordeaux Nord</name>
      <address>
        <city>Bordeaux</city>
        <zip>333000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nadine Dohollou, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centre Francois Baclesse</name>
      <address>
        <city>Caen</city>
        <zip>14000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christelle Levy, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Cêntre Hospitaler de Cholet</name>
      <address>
        <city>Cholet</city>
        <zip>49300</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alain Zannetti, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centre Georges François Leclerc</name>
      <address>
        <city>Dijon</city>
        <zip>21079</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Sylvain Ladoire, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire de Limoges</name>
      <address>
        <city>Limoges</city>
        <zip>87000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Laurence Venat-Bouvet, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Groupe hospitalier de Bretagne Sud, Hôpital du Scorff</name>
      <address>
        <city>Lorient</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Caroline CHENEAU, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centre Leon Berard</name>
      <address>
        <city>Lyon</city>
        <zip>69008</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Thomas Bachelot, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>ICM Val d'Aurelle</name>
      <address>
        <city>Montpellier</city>
        <zip>34298</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Nelly Firmin, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centre Antoine Lacassagne</name>
      <address>
        <city>Nice</city>
        <zip>06189</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jean-Marc Ferrero, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centre Paul Strauss</name>
      <address>
        <city>Strasbourg</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Thierry PETIT, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Institut Claudius Regaud</name>
      <address>
        <city>Toulouse</city>
        <zip>31100</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mony Ung, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <zip>94800</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Barbara Pistilli, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>National Institute of Oncology</name>
      <address>
        <city>Budapest</city>
        <country>Hungary</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gábor Rubovszky, MD</last_name>
      <email>garub@oncol.hu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Cro Irccs</name>
      <address>
        <city>Aviano</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Simon Spazzapan, MD</last_name>
      <email>spazzapan@cro.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>ASST Papa Giovanni XXIII</name>
      <address>
        <city>Bergamo</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Carlo Tondini, MD</last_name>
      <email>carlo.tondini@asst-pg23.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>PO Antonio Perrino Brindisi</name>
      <address>
        <city>Brindisi</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Cinieri Saverio, MD</last_name>
      <email>saverio.cinieri@ieo.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Istituto scientifico Romagnolo per lo studio e la cura</name>
      <address>
        <city>Meldola</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Andrea Rocca, MD</last_name>
      <email>andrea.rocca@irst.emr.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Istituto Europeo di Oncologia</name>
      <address>
        <city>Milan</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Elisabetta Munzone, MD</last_name>
      <email>elisabetta.munzone@ieo.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>AOU Maggiore Della Carita, University of Eastern Piedmont</name>
      <address>
        <city>Novara</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alessandra Gennari, MD</last_name>
      <email>alessandra.gennari@med.uniupo.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero-Universitaria di Parma</name>
      <address>
        <city>Parma</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Antonino Musolino, MD</last_name>
      <email>amusolino@ao.pr.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Istituti Clinici Scientifici Maugeri</name>
      <address>
        <city>Pavia</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Antonio Bernardo, MD</last_name>
      <email>antonio.bernardo@icsmaugeri.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ospedale S. Stefano</name>
      <address>
        <city>Prato</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Laura Biganzoli, MD</last_name>
      <email>laura.biganzoli@uslcentro.toscana.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>U.O. Oncologia, Ospedale Infermi</name>
      <address>
        <city>Rimini</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lorenzo Gianni, MD</last_name>
      <email>lorenzo.gianni@auslromagna.it</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Canarias</name>
      <address>
        <city>San Cristóbal de La Laguna</city>
        <state>Tenerife</state>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Josefina C Jurado, MD</last_name>
      <email>jcruzjurado@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario de Alicante</name>
      <address>
        <city>Alicante</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>José J Ponce Lorenzo, MD</last_name>
      <email>joseponcelorenzo@hotmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Vall d´Hebrón</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Meritxell Bellet Ezquerra, MD</last_name>
      <email>mbellet@vhio.net</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Instituto Catalan de Oncologia L´Hospitalet</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rafael A Villanueva Vázquez, MD</last_name>
      <email>ravillanueva@iconcologia.net</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital de Basurto</name>
      <address>
        <city>Bilbao</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Elena G Calvo, MD</last_name>
      <email>elena.galvecalvo@osakidetza.net</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Institut Català d´Oncología (ICO)</name>
      <address>
        <city>Girona</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sonia del Barco Berrón, MD</last_name>
      <email>sdelbarco@iconcologia.net</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de La Coruña</name>
      <address>
        <city>La Coruna</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Maria Eva Perez Lopez, MD</last_name>
    </contact>
    <contact_backup>
      <email>MARIA.EVA.PEREZ.LOPEZ@sergas.es</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario 12 de Octubre</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eva M Ciruelos Gíl</last_name>
      <email>eva.ciruelos@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>HU Ramón y Cajal</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Noelia Martínez Jañez, MD</last_name>
      <email>mjnoelia@hotmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Virgen de la Victoria</name>
      <address>
        <city>Málaga</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nuria R Entrena, MD</last_name>
      <email>nuriaribelles@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Virgen de la Macarena</name>
      <address>
        <city>Sevilla</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Esteban Nogales Fernandez, MD</last_name>
      <email>esteban.nogales@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Instituto Valenciano de Oncología (IVO)</name>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joaquin Gavila Gregori, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Río Hortega</name>
      <address>
        <city>Valladolid</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Javier L Puertas Álvarez, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Miguel Servet</name>
      <address>
        <city>Zaragoza</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Antonio A Torres, MD</last_name>
      <email>aantont@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Kantonsspital Baden</name>
      <address>
        <city>Baden</city>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Cornelia Leo, MD</last_name>
      <email>cornelia.leo@ksb.ch</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Brustzentrum Basel Bethesda Spital</name>
      <address>
        <city>Basel</city>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>David Thorn, MD</last_name>
      <email>dr.david.thorn@hin.ch</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Inselspital Bern</name>
      <address>
        <city>Bern</city>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Manuela Rabaglio, MD</last_name>
      <email>manuela.rabaglio@insel.ch</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centre du Sein Fribourg</name>
      <address>
        <city>Fribourg</city>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Laurant Rosset, MD</last_name>
      <phone>0041 26 347 43 07</phone>
      <email>Rossetl@hin.ch</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Fondazione Oncologia Lago Maggiore</name>
      <address>
        <city>Locarno</city>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Augusto Pedrazzini, MD</last_name>
      <email>studio@pedrazzini-oncologia.ch</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Kouros Moccia Oncologia</name>
      <address>
        <city>Locarno</city>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michail Kouros, MD</last_name>
      <email>info@kouros-moccia.ch</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Luzerner Kantonsspital</name>
      <address>
        <city>Luzern</city>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stefan Aebi, Prof.</last_name>
      <email>stefan.aebi@luks.ch</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Kantonsspital Winterthur</name>
      <address>
        <city>Winterthur</city>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Andreas Muller, MD</last_name>
      <email>andreas.mueller@ksw.ch</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>BZ Bethanien</name>
      <address>
        <city>Zürich</city>
        <zip>8001</zip>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Basil A Baettig, MD</last_name>
      <email>bbaettig@hin.ch</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Brust-Zentrum AG Zürich</name>
      <address>
        <city>Zürich</city>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Uwe Gueth, Prof.</last_name>
      <email>u.gueth@brust-zentrum.ch</email>
    </contact>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>France</country>
    <country>Hungary</country>
    <country>Italy</country>
    <country>Spain</country>
    <country>Switzerland</country>
  </location_countries>
  <reference>
    <citation>Anderson SJ, Wapnir I, Dignam JJ, Fisher B, Mamounas EP, Jeong JH, Geyer CE Jr, Wickerham DL, Costantino JP, Wolmark N. Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in patients treated by breast-conserving therapy in five National Surgical Adjuvant Breast and Bowel Project protocols of node-negative breast cancer. J Clin Oncol. 2009 May 20;27(15):2466-73. doi: 10.1200/JCO.2008.19.8424. Epub 2009 Apr 6.</citation>
    <PMID>19349544</PMID>
  </reference>
  <reference>
    <citation>Wapnir IL, Aebi S, Geyer CE, Zahrieh D, Gelber RD, Anderson SJ, Robidoux A, Bernhard J, Maibach R, Castiglione-Gertsch M, Coates AS, Piccart MJ, Clemons MJ, Costantino JP, Wolmark N; IBCSG; BIG; NSABP. A randomized clinical trial of adjuvant chemotherapy for radically resected locoregional relapse of breast cancer: IBCSG 27-02, BIG 1-02, and NSABP B-37. Clin Breast Cancer. 2008 Jun;8(3):287-92. doi: 10.3816/CBC.2008.n.035.</citation>
    <PMID>18650162</PMID>
  </reference>
  <reference>
    <citation>Borner M, Bacchi M, Goldhirsch A, Greiner R, Harder F, Castiglione M, Jungi WF, Thurlimann B, Cavalli F, Obrecht JP, et al. First isolated locoregional recurrence following mastectomy for breast cancer: results of a phase III multicenter study comparing systemic treatment with observation after excision and radiation. Swiss Group for Clinical Cancer Research. J Clin Oncol. 1994 Oct;12(10):2071-7. doi: 10.1200/JCO.1994.12.10.2071.</citation>
    <PMID>7931476</PMID>
  </reference>
  <reference>
    <citation>Aebi S, Gelber S, Anderson SJ, Lang I, Robidoux A, Martin M, Nortier JW, Paterson AH, Rimawi MF, Canada JM, Thurlimann B, Murray E, Mamounas EP, Geyer CE Jr, Price KN, Coates AS, Gelber RD, Rastogi P, Wolmark N, Wapnir IL; CALOR investigators. Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): a randomised trial. Lancet Oncol. 2014 Feb;15(2):156-63. doi: 10.1016/S1470-2045(13)70589-8. Epub 2014 Jan 16.</citation>
    <PMID>24439313</PMID>
  </reference>
  <reference>
    <citation>Wapnir IL, Price KN, Anderson SJ, Robidoux A, Martin M, Nortier JWR, Paterson AHG, Rimawi MF, Lang I, Baena-Canada JM, Thurlimann B, Mamounas EP, Geyer CE Jr, Gelber S, Coates AS, Gelber RD, Rastogi P, Regan MM, Wolmark N, Aebi S; International Breast Cancer Study Group; NRG Oncology, GEICAM Spanish Breast Cancer Group, BOOG Dutch Breast Cancer Trialists' Group; Breast International Group. Efficacy of Chemotherapy for ER-Negative and ER-Positive Isolated Locoregional Recurrence of Breast Cancer: Final Analysis of the CALOR Trial. J Clin Oncol. 2018 Apr 10;36(11):1073-1079. doi: 10.1200/JCO.2017.76.5719. Epub 2018 Feb 14.</citation>
    <PMID>29443653</PMID>
  </reference>
  <reference>
    <citation>Migliaccio I, Di Leo A, Malorni L. Cyclin-dependent kinase 4/6 inhibitors in breast cancer therapy. Curr Opin Oncol. 2014 Nov;26(6):568-75. doi: 10.1097/CCO.0000000000000129.</citation>
    <PMID>25188473</PMID>
  </reference>
  <reference>
    <citation>Wardell SE, Ellis MJ, Alley HM, Eisele K, VanArsdale T, Dann SG, Arndt KT, Primeau T, Griffin E, Shao J, Crowder R, Lai JP, Norris JD, McDonnell DP, Li S. Efficacy of SERD/SERM Hybrid-CDK4/6 Inhibitor Combinations in Models of Endocrine Therapy-Resistant Breast Cancer. Clin Cancer Res. 2015 Nov 15;21(22):5121-5130. doi: 10.1158/1078-0432.CCR-15-0360. Epub 2015 May 19.</citation>
    <PMID>25991817</PMID>
  </reference>
  <reference>
    <citation>Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, Shparyk Y, Thummala AR, Voytko NL, Fowst C, Huang X, Kim ST, Randolph S, Slamon DJ. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015 Jan;16(1):25-35. doi: 10.1016/S1470-2045(14)71159-3. Epub 2014 Dec 16.</citation>
    <PMID>25524798</PMID>
  </reference>
  <reference>
    <citation>Turner NC, Huang Bartlett C, Cristofanilli M. Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2015 Oct 22;373(17):1672-3. doi: 10.1056/NEJMc1510345. No abstract available.</citation>
    <PMID>26488700</PMID>
  </reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>January 25, 2019</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 29, 2019</study_first_posted>
  <last_update_submitted>August 28, 2023</last_update_submitted>
  <last_update_submitted_qc>August 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 29, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>hormone receptor positive breast cancer</keyword>
  <keyword>HER2 receptor negative</keyword>
  <keyword>CDK4/6 inhibitor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Palbociclib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03820830
org study id: IBCSG 59-19
secondary id: 2018-003553-19
secondary id: BIG 18-02
secondary id: WI239003
nct id: NCT03820830
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
POLAR is a phase III clinical trial, which will test the safety and efficacy of an
      investigational combination of drugs to learn whether the combination of drugs works for a
      specific cancer. Palbociclib (Ibrance®) is the name of the investigational agent, which is
      assessed together with standard anti-hormone therapy in this study. Palbociclib is used to
      treat patients with hormone receptor-positive / HER2-negative breast cancer which has spread
      beyond the original tumor and/or to other organs.

      During this study, anti-hormone therapy will consist of either a selective estrogen receptor
      modulator (such as tamoxifen) or an aromatase inhibitor (anastrozole, letrozole, exemestane)
      or fulvestrant (Faslodex®). Premenopausal women and men may also receive a drug called an
      LHRH (luteinizing hormone-releasing hormone) agonist by injection.

      It is standard of care for people with hormone receptor positive breast cancer to take
      anti-hormone therapy. The study doctor will determine the type of standard anti-hormone
      therapy that will be given during this trial.

      The purpose of the POLAR study is to compare the effect of using 3 years of palbociclib in
      combination with standard anti-hormone therapy with standard anti-hormone therapy alone and
      to evaluate the time until the breast cancer returns, if it does return.
Local or regional recurrence of breast cancer after mastectomy or lumpectomy indicates a poor
      prognosis, and accompanies or precedes distant metastasis in a high proportion of patients.
      Patients with isolated locoregional recurrences (ILRR), without evidence of distant
      metastasis hold a substantial risk of developing subsequent distant metastasis, with 5-year
      survival probabilities ranging between 45% and 80% after locoregional recurrence. These
      outcomes show the powerful negative prognostic importance of ILRR events and the need for
      treatments beyond surgical removal of the ILRR.

      Adjuvant chemotherapy and endocrine therapies reduce the risk of relapse and death in
      patients with primary breast cancer. However, few data are available to inform the
      recommendation of systemic treatment for locoregional recurrence.

      The International Breast Cancer Studies Group carried out the CALOR trial, Chemotherapy as
      Adjuvant for Locally Recurrent breast cancer (IBCSG 27-02 / BIG 1-02 / NSABP B-37), in
      collaboration with the Breast International Group (BIG) and the National Surgical Adjuvant
      Breast and Bowel Project (NSABP), to establish whether chemotherapy improves the outcome of
      patients with ILRR. An updated, final analysis of CALOR after median follow-up of about 9
      years was published in the Journal of Clinical Oncology in April 2018, which confirmed
      chemotherapy benefitted patients with resected ER-negative ILRR and did not support the use
      of chemotherapy for ER-positive ILRR.

      CALOR results strongly suggest that tailoring treatment according to the disease
      characteristics of the recurrent lesion, in this case ILRR, provides a better indication of
      the possible responsiveness to treatment than relying on the characteristics of the primary
      tumor.

      Palbociclib has been granted FDA approval in the U.S. for the treatment of
      HR-positive/HER2-negative advanced breast cancer in combination with the hormonal treatments
      letrozole and fulvestrant given the unprecedented results in terms of efficacy of two pivotal
      clinical trials (PALOMA-2 and PALOMA-3). Palbociclib and other CDK4/6 inhibitors have also
      shown a good toxicity profile and therefore are ideal candidates for combination with
      hormonal therapy. CDK4/6 pathway activation is a well-known mechanism of resistance to
      endocrine therapy, indeed CDK4/6 inhibitors have shown activity in cellular models of
      acquired resistance to endocrine therapies.

      The reason for prolonged duration of palbociclib in the adjuvant setting (2 years) comes from
      the evidence of preclinical studies where cell senescence was investigated as an appealing
      mechanism of cell death and was indeed observed in vitro after exposure of breast cancer
      cells and tumors to a combination of endocrine therapy and palbociclib. It is therefore
      hypothesized that the longer patients receive combined treatment with palbociclib and an
      antiestrogen, the more likely they may derive prolonged clinical benefit.

      Based on the results of the CALOR trial and on strong evidence of activity of the combination
      of CDK4/6 inhibitors and endocrine therapy, the hypothesis of the POLAR trial is that the
      CDK4/6 inhibitor palbociclib in combination with endocrine therapy may be active as adjuvant
      therapy in patients with HR-positive/HER2-negative resected isolated locoregional recurrence
      of breast cancer.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Duration of invasive disease free survival of all randomized participants.
time frame: Assessed from the date treatment starts until the date of first documented invasive local, regional or distant recurrence, a second invasive cancer or death, or until approximately 4 years after treatment stops.
description: Defined as the time from randomization until first appearance of invasive local, regional or distant recurrence (including invasive ipsilateral breast tumour recurrence), invasive contralateral breast cancer, a second (non-breast) invasive cancer, or death from any cause. The sites of first invasive disease events will be compared between treatment groups using a stratified log-rank test and will be tabulated.
measure: Number of participants with treatment related adverse events.
time frame: Adverse events will be collected from the date consent is signed, and during treatment until 30-60 days after treatment stops.
description: Adverse events, defined as any untoward medical occurrence, will be collected using CTCAE v5. All grades for targeted adverse events will be collected and all grades ≥3 for non-targeted adverse events. The maximum grade of each targeted adverse event during the protocol treatment phase will be determined, the frequencies summarized and tabulated according to grade and treatment assignment.
measure: Duration of breast cancer free interval of all randomized participants.
time frame: Assessed from the date of randomization until the date of first documented breast cancer recurrence, or until approximately 4 years after treatment stops.
description: Defined as the time from randomization until the date of first documented appearance of invasive local, regional or distant recurrence (including ipsilateral tumour recurrence), or invasive contralateral breast cancer.
measure: Duration of distant recurrence free interval of all randomized participants.
time frame: Assessed from the date of randomization until the date of first documented distant disease progression, or until approximately 4 years after treatment stops.
description: Defined as the time from randomization until the date of first documented distant recurrence of breast cancer.
measure: Duration of overall survival of all randomized participants.
time frame: Assessed from the date of randomization until approximately 4 years after treatment stops, or until the date of death from any cause.
description: Defined as the time from randomization until death from any cause.
arm group label: Palbociclib plus standard endocrine therapy
arm group type: Experimental
description: Palbociclib 125 mg/day tablet taken orally for 21 days, followed by 7 days rest for 3 years from randomization, plus standard endocrine therapy for at least 3 years from randomization.
arm group label: Standard endocrine therapy
arm group type: Active Comparator
description: Aromatase inhibitor (anastrozole or exemestane or letrozole) oral daily tablet, or Selective Estrogen Receptor Modulator (SERM) such as tamoxifen oral daily tablet or fulvestrant (Faslodex) injection once every 2 weeks for 3 doses then every month. Premenopausal women and men may also receive an LHRH (luteinizing hormone-releasing hormone) agonist by injection. Standard endocrine therapy will be given for at least 3 years from randomization.
intervention type: Drug
intervention name: Palbociclib 125mg
description: Palbociclib 125 mg oral tablet taken daily for 3 years from randomization
arm group label: Palbociclib plus standard endocrine therapy
other name: Ibrance
other name: PD-0332991
intervention type: Drug
intervention name: Standard endocrine therapy
description: Aromatase inhibitor (anastrozole or exemestane or letrozole) oral daily tablet, or Selective Estrogen Receptor Modulator (SERM) such as tamoxifen oral daily tablet or fulvestrant (Faslodex) injection once every 2 weeks for 3 doses then every month. Premenopausal women and men may also receive an LHRH (luteinizing hormone-releasing hormone) agonist by injection. Standard endocrine therapy will be given for at least 3 years from randomization.
arm group label: Palbociclib plus standard endocrine therapy
arm group label: Standard endocrine therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Elisabetta Munzone, MD
role: Study Chair
affiliation: European Institute of Oncology
last name: Holly Shaw
phone: +17168340900
email: ibcsg59_polar@fstrf.org
last name: Adriana Karausch
email: ibcsg59_polar@fstrf.org
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country: Austria
country: France
country: Hungary
country: Italy
country: Spain
country: Switzerland
citation: Anderson SJ, Wapnir I, Dignam JJ, Fisher B, Mamounas EP, Jeong JH, Geyer CE Jr, Wickerham DL, Costantino JP, Wolmark N. Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in patients treated by breast-conserving therapy in five National Surgical Adjuvant Breast and Bowel Project protocols of node-negative breast cancer. J Clin Oncol. 2009 May 20;27(15):2466-73. doi: 10.1200/JCO.2008.19.8424. Epub 2009 Apr 6.
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citation: Wapnir IL, Aebi S, Geyer CE, Zahrieh D, Gelber RD, Anderson SJ, Robidoux A, Bernhard J, Maibach R, Castiglione-Gertsch M, Coates AS, Piccart MJ, Clemons MJ, Costantino JP, Wolmark N; IBCSG; BIG; NSABP. A randomized clinical trial of adjuvant chemotherapy for radically resected locoregional relapse of breast cancer: IBCSG 27-02, BIG 1-02, and NSABP B-37. Clin Breast Cancer. 2008 Jun;8(3):287-92. doi: 10.3816/CBC.2008.n.035.
PMID: 18650162
citation: Borner M, Bacchi M, Goldhirsch A, Greiner R, Harder F, Castiglione M, Jungi WF, Thurlimann B, Cavalli F, Obrecht JP, et al. First isolated locoregional recurrence following mastectomy for breast cancer: results of a phase III multicenter study comparing systemic treatment with observation after excision and radiation. Swiss Group for Clinical Cancer Research. J Clin Oncol. 1994 Oct;12(10):2071-7. doi: 10.1200/JCO.1994.12.10.2071.
PMID: 7931476
citation: Aebi S, Gelber S, Anderson SJ, Lang I, Robidoux A, Martin M, Nortier JW, Paterson AH, Rimawi MF, Canada JM, Thurlimann B, Murray E, Mamounas EP, Geyer CE Jr, Price KN, Coates AS, Gelber RD, Rastogi P, Wolmark N, Wapnir IL; CALOR investigators. Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): a randomised trial. Lancet Oncol. 2014 Feb;15(2):156-63. doi: 10.1016/S1470-2045(13)70589-8. Epub 2014 Jan 16.
PMID: 24439313
citation: Wapnir IL, Price KN, Anderson SJ, Robidoux A, Martin M, Nortier JWR, Paterson AHG, Rimawi MF, Lang I, Baena-Canada JM, Thurlimann B, Mamounas EP, Geyer CE Jr, Gelber S, Coates AS, Gelber RD, Rastogi P, Regan MM, Wolmark N, Aebi S; International Breast Cancer Study Group; NRG Oncology, GEICAM Spanish Breast Cancer Group, BOOG Dutch Breast Cancer Trialists' Group; Breast International Group. Efficacy of Chemotherapy for ER-Negative and ER-Positive Isolated Locoregional Recurrence of Breast Cancer: Final Analysis of the CALOR Trial. J Clin Oncol. 2018 Apr 10;36(11):1073-1079. doi: 10.1200/JCO.2017.76.5719. Epub 2018 Feb 14.
PMID: 29443653
citation: Migliaccio I, Di Leo A, Malorni L. Cyclin-dependent kinase 4/6 inhibitors in breast cancer therapy. Curr Opin Oncol. 2014 Nov;26(6):568-75. doi: 10.1097/CCO.0000000000000129.
PMID: 25188473
citation: Wardell SE, Ellis MJ, Alley HM, Eisele K, VanArsdale T, Dann SG, Arndt KT, Primeau T, Griffin E, Shao J, Crowder R, Lai JP, Norris JD, McDonnell DP, Li S. Efficacy of SERD/SERM Hybrid-CDK4/6 Inhibitor Combinations in Models of Endocrine Therapy-Resistant Breast Cancer. Clin Cancer Res. 2015 Nov 15;21(22):5121-5130. doi: 10.1158/1078-0432.CCR-15-0360. Epub 2015 May 19.
PMID: 25991817
citation: Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, Shparyk Y, Thummala AR, Voytko NL, Fowst C, Huang X, Kim ST, Randolph S, Slamon DJ. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015 Jan;16(1):25-35. doi: 10.1016/S1470-2045(14)71159-3. Epub 2014 Dec 16.
PMID: 25524798
citation: Turner NC, Huang Bartlett C, Cristofanilli M. Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2015 Oct 22;373(17):1672-3. doi: 10.1056/NEJMc1510345. No abstract available.
PMID: 26488700
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Recurrence
mesh term: Palbociclib
sharing ipd: No