<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/NCT03822468</url>
  </required_header>
  <id_info>
    <org_study_id>CLEE011A2207</org_study_id>
    <secondary_id>2018-004234-15</secondary_id>
    <nct_id>NCT03822468</nct_id>
  </id_info>
  <brief_title>Study of 2 Ribociclib Doses in Combination With Aromatase Inhibitors in Women With HR+, HER2- Advanced Breast Cancer</brief_title>
  <acronym>AMALEE</acronym>
  <official_title>A Phase II, Multicenter, Randomized, Open-label Study to Evaluate the Safety and Efficacy of 400 mg of Ribociclib in Combination With Non-steroidal Aromatase Inhibitors for the Treatment of Pre- and Postmenopausal Women With Hormone Receptor-positive, HER2-negative Advanced Breast Cancer Who Received no Prior Therapy for Advanced Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      QT interval prolongation and neutropenia are considered to be important identified risks for&#xD;
      ribociclib. The approved dosing regimen of ribociclib is 600 mg daily (QD) on a 3 weeks on/1&#xD;
      week off schedule.&#xD;
&#xD;
      The purpose of the study is to explore whether a reduced dosing regimen of 400 mg ribociclib&#xD;
      orally QD 3 weeks on/1 week off may decrease the risk of QTc prolongation without&#xD;
      compromising the efficacy of ribociclib in combination with an NSAI in pre- and&#xD;
      postmenopausal women with HR-positive, HER2-negative aBC who have received no prior therapy&#xD;
      for advanced disease. The risks of other AEs of special interest, such as neutropenia and&#xD;
      hepatobiliary toxicity will be evaluated in this study as well.&#xD;
&#xD;
      Approximately 350 patients will be randomly assigned to one of the below treatment arms in a&#xD;
      1:1 ratio: Experimental arm (Arm 1) - Ribociclib 400 mg QD 3 weeks on/1 week off + NSAI (+&#xD;
      goserelin in premenopausal women): 175 patients Control arm (Arm 2) - Ribociclib 600 mg QD 3&#xD;
      weeks on/1 week off + NSAI (+ goserelin in premenopausal women): 175 patients Randomization&#xD;
      will be stratified by the presence of lung and/or liver metastases (yes versus no).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 11, 2019</start_date>
  <completion_date type="Anticipated">July 1, 2024</completion_date>
  <primary_completion_date type="Actual">June 11, 2021</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Response Rate (ORR)</measure>
    <time_frame>At least 6 months</time_frame>
    <description>ORR is based on local tumor assessments (RECIST version 1.1) for all patients that have been treated for at least 6 months or have discontinued the study treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Δ QTcF at Cycle 1 Day 15 (at 2h post-dose) (Key Secondary Endpoint)</measure>
    <time_frame>Cycle 1 Day 15 (2 hours post dose)</time_frame>
    <description>To evaluate QTc (with Fridericia's correction) prolongation in the experimental arm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>Approximately 36 months</time_frame>
    <description>PFS per RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical benefit rate (CBR)</measure>
    <time_frame>Approximately 36 months</time_frame>
    <description>CBR per RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to response (TTR)</measure>
    <time_frame>Approximately 36 months</time_frame>
    <description>TTR per RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR)</measure>
    <time_frame>Approximately 36 months</time_frame>
    <description>DOR per RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK) of ribociclib: Cmax</measure>
    <time_frame>Cycle 1 Day 15</time_frame>
    <description>when given in combination with NSAI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK) of ribociclib: Tmax</measure>
    <time_frame>Cycle 1 Day 15</time_frame>
    <description>when given in combination with NSAI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK) of ribociclib: AUC0 - 24h</measure>
    <time_frame>Cycle 1 Day 15</time_frame>
    <description>when given in combination with NSAI</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">376</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Ribociclib 400 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ribociclib 400 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+goserelin in premenopausal women)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ribociclib 600 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ribociclib 600 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+ goserelin in premenopausal women)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ribociclib</intervention_name>
    <description>Ribociclib will be supplied as 200 mg tablets as individual patient supply packaged bottles taken by mouth.</description>
    <arm_group_label>Ribociclib 400 mg</arm_group_label>
    <arm_group_label>Ribociclib 600 mg</arm_group_label>
    <other_name>LEE011</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Letrozole or Anastrozole</intervention_name>
    <description>Letrozole 2.5 mg by mouth QD continuously or anastrozole 1 mg by mouth QD continuously (investigator choice)</description>
    <arm_group_label>Ribociclib 400 mg</arm_group_label>
    <arm_group_label>Ribociclib 600 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Goserelin</intervention_name>
    <description>Goserelin 3.6 mg subcutaneously once every 4 weeks (pre-menopausal women only)</description>
    <arm_group_label>Ribociclib 400 mg</arm_group_label>
    <arm_group_label>Ribociclib 600 mg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion criteria:&#xD;
&#xD;
        Patient has advanced (loco-regionally recurrent or metastatic) breast cancer not amenable&#xD;
        to curative therapy.&#xD;
&#xD;
        Patient has a histologically and/or cytologically confirmed diagnosis of ER-positive and/or&#xD;
        PgR-positive breast cancer based on the most recently analyzed tissue sample, and all&#xD;
        tested by local laboratory.&#xD;
&#xD;
        Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or&#xD;
        an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH,&#xD;
        or SISH) test is required by local laboratory testing and based on the most recently&#xD;
        analyzed tissue sample.&#xD;
&#xD;
        Patient must have measurable disease, i.e., at least one measurable lesion according to&#xD;
        RECIST version 1.1. (a lesion in a previously irradiated site may only be counted as a&#xD;
        target lesion if there is clear evidence of progression since the irradiation).&#xD;
&#xD;
        Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.&#xD;
&#xD;
        Standard 12-lead ECG values defined as the mean of the triplicate ECGs and assessed by the&#xD;
        central laboratory:&#xD;
&#xD;
          -  QTcF interval at screening &lt; 450 ms (QT interval using Fridericia's correction)&#xD;
&#xD;
          -  Mean resting heart rate 50 to 90 bpm (determined from the ECG)&#xD;
&#xD;
        Women of childbearing potential (CBP), defined as all women physiologically capable of&#xD;
        becoming pregnant, must have confirmed negative serum pregnancy test (for β-hCG) within 14&#xD;
        days prior to randomization.&#xD;
&#xD;
        Women of CBP must be willing to use highly effective methods of contraception.&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
        Patient with symptomatic visceral disease or any disease burden that makes the patient&#xD;
        ineligible for endocrine therapy per the investigator's judgment.&#xD;
&#xD;
        Patient who received any prior systemic anti-cancer therapy(including endocrine therapy,&#xD;
        chemotherapy, prior CDK4/6 inhibitors) for aBC. Patients who received neo-/adjuvant therapy&#xD;
        for breast cancer are eligible.&#xD;
&#xD;
        Patient is concurrently using other anti-cancer therapy.&#xD;
&#xD;
        Patient has had major surgery within 14 days prior to starting study drug or has not&#xD;
        recovered from major toxicities.&#xD;
&#xD;
        Patient has received extended-field radiotherapy ≤ 4 weeks or limited field radiotherapy ≤&#xD;
        2 weeks prior to randomization, and has not recovered to grade 1 or better from related&#xD;
        side effects of such therapy (with the exception of alopecia or other toxicities not&#xD;
        considered a safety risk for the patient at investigator's discretion). Patients in whom ≥&#xD;
        25% of the bone marrow has been previously irradiated are also excluded.&#xD;
&#xD;
        Patient has a concurrent malignancy or malignancy within 3 years of the randomization date,&#xD;
        with the exception of adequately treated basal or squamous cell skin carcinoma, or&#xD;
        curatively resected cervical carcinoma in situ.&#xD;
&#xD;
        Patients with central nervous system (CNS) involvement unless they meet specific stability&#xD;
        criteria.&#xD;
&#xD;
        Patient has clinically significant, uncontrolled heart disease and/or cardiac&#xD;
        repolarization abnormality.&#xD;
&#xD;
        Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to&#xD;
        starting study drug, and has not fully recovered from side effects of such treatment.&#xD;
&#xD;
        Other protocol-defined Inclusion/Exclusion may apply.&#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>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Southern Cancer Center PC .</name>
      <address>
        <city>Mobile</city>
        <state>Alabama</state>
        <zip>36608</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Marin Cancer Care</name>
      <address>
        <city>Greenbrae</city>
        <state>California</state>
        <zip>94904</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers Rocky Mountain Cancer Ctr (50)</name>
      <address>
        <city>Longmont</city>
        <state>Colorado</state>
        <zip>80501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Retina Institute</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weinberg Cancer Institute at Franklin Square Hospital</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21237-3998</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nebraska Hematology-Oncology, P.C.</name>
      <address>
        <city>Lincoln</city>
        <state>Nebraska</state>
        <zip>68506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nebraska Cancer Specialists Oncology Hematology West</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68154</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Cancer Centers of Nevada CCC of Nevada Henderson (4)</name>
      <address>
        <city>Henderson</city>
        <state>Nevada</state>
        <zip>89052</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York Oncology Hematology SC</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <zip>12208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montefiore Medical Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10467</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai School of Medicine CFTY720D2306</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Millennium Research Clin Develop .</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77090</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology</name>
      <address>
        <city>McAllen</city>
        <state>Texas</state>
        <zip>78503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwest Medical Specialties Dept.ofNW Med. Specialties</name>
      <address>
        <city>Tacoma</city>
        <state>Washington</state>
        <zip>98405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>San Juan</city>
        <zip>J5402DIL</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Innsbruck</city>
        <zip>A-6020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Linz</city>
        <zip>4010</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Salzburg</city>
        <zip>5020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Vienna</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Edegem</city>
        <state>Antwerpen</state>
        <zip>2650</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Namur</city>
        <zip>5000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Goiania</city>
        <state>GO</state>
        <zip>74605-070</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Natal</city>
        <state>RN</state>
        <zip>59075 740</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Florianopolis</city>
        <state>Santa Catarina</state>
        <zip>88034 000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sao Paulo</city>
        <state>SP</state>
        <zip>01317 000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sao Paulo</city>
        <state>SP</state>
        <zip>04014-002</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sao Jose do Rio Preto</city>
        <zip>15090 000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Plovdiv</city>
        <zip>4004</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sofia</city>
        <zip>1303</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sofia</city>
        <zip>1756</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Cambridge</city>
        <state>Ontario</state>
        <zip>N1R 3G2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Valledupar</city>
        <state>Cesar</state>
        <zip>5602310</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ibague</city>
        <state>Tolima</state>
        <zip>730006</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bogota</city>
        <zip>110131</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bogota</city>
        <zip>110221</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Monteria</city>
        <zip>230002</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>San Jose</city>
        <zip>95008</zip>
        <country>Costa Rica</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Brno</city>
        <state>Czech Republic</state>
        <zip>656 53</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Praha 5</city>
        <zip>150 06</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Helsinki</city>
        <zip>00029</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tampere</city>
        <zip>FIN-33521</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Besancon Cedex</city>
        <zip>25030</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Caen</city>
        <zip>14021</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Clermont Ferrand</city>
        <zip>63011</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lyon Cedex 08</city>
        <zip>69373</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Marseille</city>
        <zip>13273</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Montpellier</city>
        <zip>34298</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Saint Herblain</city>
        <zip>44805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Strasbourg</city>
        <zip>F 67085</zip>
        <country>France</country>
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  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Valenciennes</city>
        <zip>59300</zip>
        <country>France</country>
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  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Langen</city>
        <state>Hessen</state>
        <zip>63225</zip>
        <country>Germany</country>
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  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Augsburg</city>
        <zip>86150</zip>
        <country>Germany</country>
      </address>
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  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Berlin</city>
        <zip>13581</zip>
        <country>Germany</country>
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  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bonn</city>
        <zip>53111</zip>
        <country>Germany</country>
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  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Dresden</city>
        <zip>01127</zip>
        <country>Germany</country>
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  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Dresden</city>
        <zip>01307</zip>
        <country>Germany</country>
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  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Essen</city>
        <zip>45136</zip>
        <country>Germany</country>
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  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tuebingen</city>
        <zip>72076</zip>
        <country>Germany</country>
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  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Weiden</city>
        <zip>92637</zip>
        <country>Germany</country>
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    <facility>
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        <zip>H 1122</zip>
        <country>Hungary</country>
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  <location>
    <facility>
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      <address>
        <city>Debrecen</city>
        <zip>4032</zip>
        <country>Hungary</country>
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  <location>
    <facility>
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      <address>
        <city>Szolnok</city>
        <zip>H-5000</zip>
        <country>Hungary</country>
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  <location>
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      <address>
        <city>Raipur</city>
        <state>Chhattisgarh</state>
        <zip>492001</zip>
        <country>India</country>
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  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Nagpur</city>
        <state>Maharashtra</state>
        <zip>441108</zip>
        <country>India</country>
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  <location>
    <facility>
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      <address>
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        <state>Orissa</state>
        <zip>751007</zip>
        <country>India</country>
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  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Delhii</city>
        <zip>110 085</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Mumbai</city>
        <zip>400 012</zip>
        <country>India</country>
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    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Amman</city>
        <zip>11941</zip>
        <country>Jordan</country>
      </address>
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  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kaunas</city>
        <state>LTU</state>
        <zip>LT 50161</zip>
        <country>Lithuania</country>
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    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Vilnius</city>
        <zip>LT-08660</zip>
        <country>Lithuania</country>
      </address>
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  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Trujillo</city>
        <state>La Libertad</state>
        <zip>13011</zip>
        <country>Peru</country>
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  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>San Borja</city>
        <state>Lima</state>
        <zip>41</zip>
        <country>Peru</country>
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    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>San Isidro</city>
        <state>Lima</state>
        <zip>27</zip>
        <country>Peru</country>
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    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>San Miguel</city>
        <state>Lima</state>
        <zip>32</zip>
        <country>Peru</country>
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  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lisbon</city>
        <zip>1400 038</zip>
        <country>Portugal</country>
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  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Loures</city>
        <zip>2674514</zip>
        <country>Portugal</country>
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  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Porto</city>
        <zip>4200-072</zip>
        <country>Portugal</country>
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  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Arkhangelsk</city>
        <zip>163045</zip>
        <country>Russian Federation</country>
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  </location>
  <location>
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      <name>Novartis Investigative Site</name>
      <address>
        <city>Moscow</city>
        <zip>111123</zip>
        <country>Russian Federation</country>
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  <location>
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      <address>
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        <zip>115478</zip>
        <country>Russian Federation</country>
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      <address>
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        <zip>197758</zip>
        <country>Russian Federation</country>
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      <name>Novartis Investigative Site</name>
      <address>
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        <zip>189646</zip>
        <country>Russian Federation</country>
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      <address>
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        <zip>7500</zip>
        <country>South Africa</country>
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      <name>Novartis Investigative Site</name>
      <address>
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        <zip>2196</zip>
        <country>South Africa</country>
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      <name>Novartis Investigative Site</name>
      <address>
        <city>Parktown</city>
        <zip>2193</zip>
        <country>South Africa</country>
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      <name>Novartis Investigative Site</name>
      <address>
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        <zip>112 19</zip>
        <country>Sweden</country>
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  <location>
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      <name>Novartis Investigative Site</name>
      <address>
        <city>Stockholm</city>
        <zip>SE-118 83</zip>
        <country>Sweden</country>
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  <location>
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      <address>
        <city>Uppsala</city>
        <zip>751 85</zip>
        <country>Sweden</country>
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  </location>
  <location>
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      <name>Novartis Investigative Site</name>
      <address>
        <city>Bangkok</city>
        <zip>10700</zip>
        <country>Thailand</country>
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  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Chiang Mai</city>
        <zip>50200</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Austria</country>
    <country>Belgium</country>
    <country>Brazil</country>
    <country>Bulgaria</country>
    <country>Canada</country>
    <country>Colombia</country>
    <country>Costa Rica</country>
    <country>Czechia</country>
    <country>Finland</country>
    <country>France</country>
    <country>Germany</country>
    <country>Hungary</country>
    <country>India</country>
    <country>Jordan</country>
    <country>Lithuania</country>
    <country>Peru</country>
    <country>Portugal</country>
    <country>Russian Federation</country>
    <country>South Africa</country>
    <country>Sweden</country>
    <country>Thailand</country>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>January 28, 2019</study_first_submitted>
  <study_first_submitted_qc>January 28, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <disposition_first_submitted>May 9, 2022</disposition_first_submitted>
  <disposition_first_submitted_qc>May 9, 2022</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">May 13, 2022</disposition_first_posted>
  <last_update_submitted>June 30, 2023</last_update_submitted>
  <last_update_submitted_qc>June 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Breast Cancer</keyword>
  <keyword>HR-positive</keyword>
  <keyword>HER2-negative</keyword>
  <keyword>ER-positive</keyword>
  <keyword>advanced breast cancer</keyword>
  <keyword>ribociclib</keyword>
  <keyword>LEE011</keyword>
  <keyword>premenopausal</keyword>
  <keyword>postmenopausal</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>Anastrozole</mesh_term>
    <mesh_term>Goserelin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.&#xD;
This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT03822468
org study id: CLEE011A2207
secondary id: 2018-004234-15
nct id: NCT03822468
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
QT interval prolongation and neutropenia are considered to be important identified risks for
      ribociclib. The approved dosing regimen of ribociclib is 600 mg daily (QD) on a 3 weeks on/1
      week off schedule.

      The purpose of the study is to explore whether a reduced dosing regimen of 400 mg ribociclib
      orally QD 3 weeks on/1 week off may decrease the risk of QTc prolongation without
      compromising the efficacy of ribociclib in combination with an NSAI in pre- and
      postmenopausal women with HR-positive, HER2-negative aBC who have received no prior therapy
      for advanced disease. The risks of other AEs of special interest, such as neutropenia and
      hepatobiliary toxicity will be evaluated in this study as well.

      Approximately 350 patients will be randomly assigned to one of the below treatment arms in a
      1:1 ratio: Experimental arm (Arm 1) - Ribociclib 400 mg QD 3 weeks on/1 week off + NSAI (+
      goserelin in premenopausal women): 175 patients Control arm (Arm 2) - Ribociclib 600 mg QD 3
      weeks on/1 week off + NSAI (+ goserelin in premenopausal women): 175 patients Randomization
      will be stratified by the presence of lung and/or liver metastases (yes versus no).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Response Rate (ORR)
time frame: At least 6 months
description: ORR is based on local tumor assessments (RECIST version 1.1) for all patients that have been treated for at least 6 months or have discontinued the study treatment.
measure: Δ QTcF at Cycle 1 Day 15 (at 2h post-dose) (Key Secondary Endpoint)
time frame: Cycle 1 Day 15 (2 hours post dose)
description: To evaluate QTc (with Fridericia's correction) prolongation in the experimental arm
measure: Progression-free survival (PFS)
time frame: Approximately 36 months
description: PFS per RECIST 1.1
measure: Clinical benefit rate (CBR)
time frame: Approximately 36 months
description: CBR per RECIST 1.1
measure: Time to response (TTR)
time frame: Approximately 36 months
description: TTR per RECIST 1.1
measure: Duration of response (DOR)
time frame: Approximately 36 months
description: DOR per RECIST 1.1
measure: Pharmacokinetics (PK) of ribociclib: Cmax
time frame: Cycle 1 Day 15
description: when given in combination with NSAI
measure: Pharmacokinetics (PK) of ribociclib: Tmax
time frame: Cycle 1 Day 15
description: when given in combination with NSAI
measure: Pharmacokinetics (PK) of ribociclib: AUC0 - 24h
time frame: Cycle 1 Day 15
description: when given in combination with NSAI
arm group label: Ribociclib 400 mg
arm group type: Experimental
description: Ribociclib 400 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+goserelin in premenopausal women)
arm group label: Ribociclib 600 mg
arm group type: Active Comparator
description: Ribociclib 600 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+ goserelin in premenopausal women)
intervention type: Drug
intervention name: Ribociclib
description: Ribociclib will be supplied as 200 mg tablets as individual patient supply packaged bottles taken by mouth.
arm group label: Ribociclib 400 mg
arm group label: Ribociclib 600 mg
other name: LEE011
intervention type: Drug
intervention name: Letrozole or Anastrozole
description: Letrozole 2.5 mg by mouth QD continuously or anastrozole 1 mg by mouth QD continuously (investigator choice)
arm group label: Ribociclib 400 mg
arm group label: Ribociclib 600 mg
intervention type: Drug
intervention name: Goserelin
description: Goserelin 3.6 mg subcutaneously once every 4 weeks (pre-menopausal women only)
arm group label: Ribociclib 400 mg
arm group label: Ribociclib 600 mg
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
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country: Argentina
country: Austria
country: Belgium
country: Brazil
country: Bulgaria
country: Canada
country: Colombia
country: Costa Rica
country: Czechia
country: Finland
country: France
country: Germany
country: Hungary
country: India
country: Jordan
country: Lithuania
country: Peru
country: Portugal
country: Russian Federation
country: South Africa
country: Sweden
country: Thailand
country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Letrozole
mesh term: Anastrozole
mesh term: Goserelin
sharing ipd: Yes
ipd description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.