<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/NCT03839823</url>
  </required_header>
  <id_info>
    <org_study_id>CLEE011A3201C</org_study_id>
    <nct_id>NCT03839823</nct_id>
  </id_info>
  <brief_title>Study to Compare the Combination of Ribociclib Plus Goserelin Acetate With Hormonal Therapy Versus Combination Chemotherapy in Premenopausal or Perimenopausal Patients With Advanced or Metastatic Breast Cancer</brief_title>
  <acronym>RIGHT Choice</acronym>
  <official_title>A Phase II Randomized Study of the Combination of Ribociclib Plus Goserelin Acetate With Hormonal Therapy Versus Physician Choice Chemotherapy in Premenopausal or Perimenopausal Patients With Hormone Receptor-positive/ HER2-negative Inoperable Locally Advanced or Metastatic Breast Cancer</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>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To compare the combination of Ribociclib plus goserelin acetate with hormonal therapy versus&#xD;
      combination chemotherapy in premenopausal or perimenopausal patients with advanced or&#xD;
      metastatic breast cancer&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A phase II randomized study of the combination of Ribociclib plus goserelin acetate with&#xD;
      Hormonal Therapy versus physician choice chemotherapy in premenopausal or perimenopausal&#xD;
      patients with hormone receptor-positive/ HER2-negative inoperable locally advanced or&#xD;
      metastatic breast cancer - RIGHT Choice Study&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 25, 2019</start_date>
  <completion_date type="Actual">May 10, 2023</completion_date>
  <primary_completion_date type="Actual">April 12, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>This is a randomized, phase II, open label, multi-center trial comparing the combination of NSAI (letrozole or anastrozole) + goserelin + ribociclib versus combination chemotherapy (either of docetaxel/capecitabine or paclitaxel/gemcitabine or capecitabine/vinorelbine). Premenopausal or perimenopausal women with HR+, HER2- negative, advanced breast cancer with ECOG performance status of 0 to 2 and having symptomatic visceral metastases, or rapid progression of disease or impending visceral compromise, or markedly symptomatic non visceral disease will be considered for this study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>Up to approximately 34 months</time_frame>
    <description>Progression-free survival is defined as the time from the date of randomization to the date of the first documented progression as per local review and according to RECIST 1.1 or death due to any cause.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to treatment failure</measure>
    <time_frame>Up to approximately 34 months</time_frame>
    <description>Time to treatment failure is defined as the time from the date of randomization/start of treatment to the earliest of date of progression, date of death due to any cause, change to other anti-cancer therapy, or date of discontinuation due to reasons other than 'Protocol violation' or 'Administrative problems'.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response rate (ORR)</measure>
    <time_frame>Up to approximately 34 months</time_frame>
    <description>Overall response rate (ORR) is defined as the proportion of patients whose best overall response is either complete response (CR) or partial response (PR), as per local review and according to RECIST 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical benefit rate</measure>
    <time_frame>Up to approximately 34 months</time_frame>
    <description>Clinical benefit rate is defined as the proportion of patients with a best overall response of CR, or PR or stable disease, lasting for a duration of at least 24 weeks, as defined by RECIST 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to response</measure>
    <time_frame>Up to approximately 34 months</time_frame>
    <description>Time to response is defined as the time from the date of randomization to the first documented response of either CR or PR, which must be subsequently confirmed, as defined by RECIST 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Up to approximately 46 months</time_frame>
    <description>Overall survival is defined as the time from the date of randomization to the date of death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency/severity of adverse events, lab abnormalities.</measure>
    <time_frame>Up to approximately 46 months</time_frame>
    <description>Safety of ribociclib in combination with NSAI and goserelin, and combination chemotherapies</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in the global health status/QOL scale score by using FACT-B questionnaire</measure>
    <time_frame>Up to approximately 46 months</time_frame>
    <description>Functional Assessment of Cancer Therapy - Breast (FACT-B) will be collected to assess health-related QoL, health status, functioning, disease symptoms, side effects, and cancer-related pain.&#xD;
Descriptive statistics will be used to summarize the overall score at each scheduled assessment time point. Additionally, change from baseline at the time of each assessment will be summarized.&#xD;
The distribution of time to definitive 10% deterioration in the global health status from FACT-B questionnaire will be assessed in the two treatment arms. Scores range from 0 to 4. no subscale. 0 score is the worst for social/family and functional wellbeing and 4 is the worst for physical, emotional wellbeing and additional concerns.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>3-month treatment failure rate</measure>
    <time_frame>Up to approximately 34 months</time_frame>
    <description>Treatment failure rate is defined as the proportion of patients who discontinued the study treatment due to progressive disease, death due to any cause, change to other anti-cancer therapy, or discontinuation due to reasons other than protocol violation or administrative problems.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">223</enrollment>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Comparator arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Combination chemotherapies of docetaxel/capecitabine, paclitaxel/gemcitabine or capecitabine/vinorelbine will be administer to patients enrolled in the control group. The chemotherapy regimen will be decided by the treating physician.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ribociclib arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Combination of non-steroidal aromatase inhibitor: NSAI (letrozole or anastrozole) + goserelin + ribociclib.&#xD;
Ribociclib (600 mg) is dosed orally for the first 21 days out of a 28 day cycle.&#xD;
Letrozole (2.5 mg) or anastrozole (1 mg) are dosed orally daily (28 days out of the 28 day cycle).&#xD;
Goserelin (3.6 mg) is continuously released via a subcutaneous implant injected on Day 1 of each 28 day cycle (regardless of ribociclib treatment cycle) with an administration window of + 3 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Docetaxel / Capecitabine</intervention_name>
    <description>Docetaxel (IV Infusion) / Capecitabine (Tablets for oral use):&#xD;
Docetaxel once, on day 1 of the 3-weeks cycle. Capecitabine twice daily, on Days 1 to 14, followed by a 1-week rest period, in 3 weeks cycle.&#xD;
Docetaxel (60 - 75 mg/m²)/capecitabine (1600 - 2500 mg/m²/day)</description>
    <arm_group_label>Comparator arm</arm_group_label>
    <other_name>Combination chemotherapy group.</other_name>
    <other_name>The chemotherapy regimen will be decided by the treating physician.</other_name>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Capecitabine / Vinorelbine</intervention_name>
    <description>Capecitabine (Tablets for oral use) / Vinorelbine (Capsule for Oral use/IV infusion ).&#xD;
Capecitabine twice daily on day 1 to 14, followed by a 1-week rest period, in 3 weeks cycle.&#xD;
Vinorelbine, once, on Day 1 and Day 8 in 3 weeks cycles.&#xD;
Capecitabine (1600 - 2500 mg/m2/day)/vinorelbine (60 to 80 mg/m2/day [oral] or (25 to 30 mg/m2 [IV infusion]</description>
    <arm_group_label>Comparator arm</arm_group_label>
    <other_name>Combination chemotherapy group.</other_name>
    <other_name>The chemotherapy regimen will be decided by the treating physician.</other_name>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Paclitaxel / Gemcitabine</intervention_name>
    <description>Paclitaxel (IV Infusion) / Gemcitabine (IV Infusion):&#xD;
Paclitaxel via 3-hour intravenous (IV) infusion on Day 1 in 3-weeks cycles, OR Paclitaxel via 1 hour intravenous (IV) infusion on Day 1 and day 8- in 3-weeks cycles.&#xD;
Gemcitabine at via 30 minute IV infusion on Day 1 and Day 8 in 3 weeks cycles.&#xD;
Paclitaxel (175 mg/m2) (on Day 1 in 3-weeks cycles)/ gemcitabine (1000 - 1250 mg/m2)&#xD;
OR&#xD;
Paclitaxel (80 - 90 mg/m2) (on Day 1 and Day 8 in 3-weeks cycles) / gemcitabine (800 - 1250 mg/m2)</description>
    <arm_group_label>Comparator arm</arm_group_label>
    <other_name>Combination chemotherapy group.</other_name>
    <other_name>The chemotherapy regimen will be decided by the treating physician.</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ribociclib</intervention_name>
    <description>Dose: 600 mg (200 mg * 3) Days 1 to 21 of each 28 day cycle Tablets for oral use</description>
    <arm_group_label>Ribociclib arm</arm_group_label>
    <other_name>Endocrine treatment arm:</other_name>
    <other_name>NSAI + goserelin+ ribociclib</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Letrozole OR Anastrozole</intervention_name>
    <description>Letrozole:&#xD;
Dose: 2.5 mg All days of every cycle without interruption). Tablets for oral use&#xD;
Anastrozole:&#xD;
dose: 1 mg All days of every cycle without interruption. Tablets for oral use&#xD;
The NSAI (letrozole or anastrozole) will be decided by the treating physician.</description>
    <arm_group_label>Ribociclib arm</arm_group_label>
    <other_name>Endocrine treatment arm:</other_name>
    <other_name>NSAI + goserelin+ ribociclib</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Goserelin</intervention_name>
    <description>Dose: 3.6 mg Day 1 of each 28 day cycle (regardless of ribociclib treatment cycle) with an administration window of + 3 days.&#xD;
Subcutaneous implant</description>
    <arm_group_label>Ribociclib arm</arm_group_label>
    <other_name>Endocrine treatment arm:</other_name>
    <other_name>NSAI + goserelin+ ribociclib</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        INCLUSION CRITERIA&#xD;
&#xD;
          1. Patient is an adult female ≥ 18 years old and &lt; 60 years old at the time of informed&#xD;
             consent.&#xD;
&#xD;
          2. Patient has a histologically and/or cytologically confirmed diagnosis of&#xD;
             estrogen-receptor positive and/or progesterone receptor positive breast cancer based&#xD;
             on the most recently analyzed tissue sample and all tested by local laboratory. ER&#xD;
             should be more than 10% ER positive or Allred ≥5 by local laboratory testing.&#xD;
&#xD;
          3. Patient has HER2-negative breast cancer defined as a negative in situ hybridization&#xD;
             test or an IHC status of 0, 1 + or 2 + If IHC is 2 +, a negative in situ hybridization&#xD;
             (FISH, CISH, or SISH) test is required by local laboratory testing and based on the&#xD;
             most recently analyzed tissue sample.&#xD;
&#xD;
          4. Women with inoperable locally advanced or metastatic breast cancer not amenable to&#xD;
             curative therapy. Patients must fulfill at least one of the following criteria to be&#xD;
             considered that combination chemotherapy is needed according to PI's judgment.&#xD;
             However, for patients who are eligible under inoperable locally advanced breast cancer&#xD;
             or criteria 4c, the recruitment is stopped to enrich patient population with visceral&#xD;
             metastases.&#xD;
&#xD;
               -  Symptomatic visceral metastases&#xD;
&#xD;
               -  Rapid progression of disease or impending visceral compromise.&#xD;
&#xD;
               -  Markedly symptomatic non visceral disease if the treating physician opt to give&#xD;
                  chemotherapy for rapid palliation of patients symptoms.&#xD;
&#xD;
          5. Patient is premenopausal or perimenopausal at the time of study entry.&#xD;
&#xD;
               1. Premenopausal status is defined as either:&#xD;
&#xD;
                    -  Patient had last menstrual period within the last 12 months. OR&#xD;
&#xD;
                    -  If on tamoxifen within the past 14 days, plasma estradiol and FSH are in the&#xD;
                       premenopausal range, according to local laboratory definition.&#xD;
&#xD;
                    -  In case of therapy induced amenorrhea, plasma estradiol and/or FSH are in&#xD;
                       the premenopausal range according to local laboratory definition.&#xD;
&#xD;
                    -  Patients who have undergone bilateral oophorectomy are not eligible.&#xD;
&#xD;
               2. Perimenopausal status is defined as neither premenopausal nor postmenopausal&#xD;
&#xD;
          6. Patients must have not received neither prior hormonal therapy nor chemotherapy for&#xD;
             advanced breast cancer, except LHRH agonist. Patients who received ≤ 14 days of&#xD;
             tamoxifen or a NSAI (letrozole or anastrozole) with or without LHRH agonist for&#xD;
             advanced breast cancer prior to randomization are eligible. Patient must have&#xD;
             measurable disease.&#xD;
&#xD;
        EXCLUSION CRITERIA;&#xD;
&#xD;
          1. Patient has received prior systemic anti-cancer therapy (including hormonal therapy&#xD;
             and chemotherapy, or any CDK4/6 inhibitor for advanced breast cancer.&#xD;
&#xD;
               -  Patients who received (neo) adjuvant therapy for breast cancer are eligible. If&#xD;
                  the prior neo (adjuvant) therapy included aromatase inhibitors, the treatment&#xD;
                  free interval must be greater than 12 months from the completion of aromatase&#xD;
                  inhibitor treatment until randomization.&#xD;
&#xD;
               -  If patients have disease recurrence during adjuvant tamoxifen treatment, disease&#xD;
                  free interval (defined as duration between the date of patient received complete&#xD;
                  tumor resection for primary breast cancer lesion to the date of disease&#xD;
                  recurrence documented) must be greater than 12 months.&#xD;
&#xD;
               -  Patients who are receiving ≤ 14 days of tamoxifen or NSAI or LHRH agonists ≤ 28&#xD;
                  days for advanced breast cancer prior to randomization are eligible.&#xD;
&#xD;
          2. Patient has received extended-field radiotherapy ≤ 2 weeks prior to randomization or&#xD;
             limited field radiotherapy ≤ 2 weeks prior to randomization, and has not recovered to&#xD;
             grade 1 or better from related side effects of such therapy (with the exception of&#xD;
             alopecia or other toxicities not considered a safety risk for the patient at&#xD;
             investigator's discretion). Patient from whom ≥ 25% of the bone marrow has been&#xD;
             previously irradiated are also excluded.&#xD;
&#xD;
          3. Patient has a concurrent malignancy or malignancy within 3 years of randomization,&#xD;
             with the exception of adequately treated, basal or squamous cell skin carcinoma or&#xD;
             curatively resected cervical cancer in situ.&#xD;
&#xD;
          4. Patients who have lung metastases with oxygen demand in resting status.&#xD;
&#xD;
          5. Patients who have liver metastases with bilirubin &gt; 1.5 ULN.&#xD;
&#xD;
          6. Patients with CNS involvement unless they meet ALL of the following criteria:&#xD;
&#xD;
               -  At least 4 weeks from prior therapy completion (including radiation and/or&#xD;
                  surgery) to starting the study treatment.&#xD;
&#xD;
               -  Clinically stable CNS tumor at the time of screening and not receiving steroids&#xD;
                  and/or enzyme inducing anti-epileptic medications for brain metastases&#xD;
&#xD;
               -  Leptomeningeal metastases is not allowed, even with stable clinical condition&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Patient is an adult female ≥ 18 years old and &lt; 60 years old at the time of informed consent.</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>59 Years</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>Novartis Investigative Site</name>
      <address>
        <city>Cairo</city>
        <zip>11566</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Cairo</city>
        <zip>12655</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Cairo</city>
        <zip>3247511</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Giza</city>
        <zip>11451</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bangalore</city>
        <state>Karnataka</state>
        <zip>560 095</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Pune</city>
        <state>Maharashtra</state>
        <zip>411004</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hyderabad</city>
        <state>Telangana</state>
        <zip>500082</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kolkata</city>
        <state>West Bengal</state>
        <zip>700099</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>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>New Delhi</city>
        <zip>110029</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Amman</city>
        <zip>11941</zip>
        <country>Jordan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Beirut</city>
        <zip>1107 2020</zip>
        <country>Lebanon</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Saida</city>
        <zip>652</zip>
        <country>Lebanon</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tripoli</city>
        <zip>1434</zip>
        <country>Lebanon</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Johor Bahru</city>
        <state>Johor</state>
        <zip>81100</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kota Kinabalu</city>
        <state>Sabah</state>
        <zip>88586</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kuching</city>
        <state>Sarawak</state>
        <zip>93586</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kuala Lumpur</city>
        <state>Wilayah Persekutuan</state>
        <zip>50586</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Pulau Pinang</city>
        <zip>10990</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Moscow</city>
        <zip>111123</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Moscow</city>
        <zip>115478</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Pushkin Saint Petersburg</city>
        <zip>196603</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>St Petersburg</city>
        <zip>197758</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Riyadh</city>
        <zip>11211</zip>
        <country>Saudi Arabia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Singapore</city>
        <zip>168583</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Singapore</city>
        <zip>188770</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Singapore</city>
        <zip>258499</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Durban</city>
        <state>Kwazulu Natal</state>
        <zip>4091</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Pretoria</city>
        <zip>0002</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Pretoria</city>
        <zip>0081</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kaohsiung City</city>
        <zip>83301</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Taichung</city>
        <zip>40447</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tainan</city>
        <zip>70403</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Taipei</city>
        <zip>10002</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Taipei</city>
        <zip>10449</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Taipei</city>
        <zip>11217</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Taipei</city>
        <zip>114</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Taoyuan</city>
        <zip>33305</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Songkhla</city>
        <state>Hat Yai</state>
        <zip>90110</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bangkok</city>
        <zip>10310</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bangkok</city>
        <zip>10400</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Chiang Mai</city>
        <zip>50200</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ankara</city>
        <zip>06520</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Antalya</city>
        <zip>07059</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Cankaya Ankara</city>
        <zip>06560</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Istanbul</city>
        <zip>34381</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Istanbul</city>
        <zip>34457</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Izmir</city>
        <zip>35040</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kecioren Ankara</city>
        <zip>06010</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Malatya</city>
        <zip>44280</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hanoi</city>
        <zip>100000</zip>
        <country>Vietnam</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
    <country>India</country>
    <country>Jordan</country>
    <country>Lebanon</country>
    <country>Malaysia</country>
    <country>Russian Federation</country>
    <country>Saudi Arabia</country>
    <country>Singapore</country>
    <country>South Africa</country>
    <country>Taiwan</country>
    <country>Thailand</country>
    <country>Turkey</country>
    <country>Vietnam</country>
  </location_countries>
  <removed_countries>
    <country>Philippines</country>
  </removed_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>January 24, 2019</study_first_submitted>
  <study_first_submitted_qc>February 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <last_update_submitted>June 23, 2023</last_update_submitted>
  <last_update_submitted_qc>June 23, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 26, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HR-positive</keyword>
  <keyword>HER2-negative</keyword>
  <keyword>advanced breast cancer</keyword>
  <keyword>Ribociclib</keyword>
  <keyword>NSAI</keyword>
  <keyword>Goserelin</keyword>
  <keyword>Docetaxel / capecitabine</keyword>
  <keyword>Paclitaxel/gemcitabine</keyword>
  <keyword>Capecitabine/vinorelbine</keyword>
  <keyword>CDK4/6 inhibitors</keyword>
  <keyword>Phase II</keyword>
  <keyword>ER-positive</keyword>
  <keyword>PR-positive</keyword>
  <keyword>Premenopausal</keyword>
  <keyword>Perimenopausal</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>Paclitaxel</mesh_term>
    <mesh_term>Vinorelbine</mesh_term>
    <mesh_term>Docetaxel</mesh_term>
    <mesh_term>Gemcitabine</mesh_term>
    <mesh_term>Capecitabine</mesh_term>
    <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 review 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 availability is according to the criteria and process described on www.clinicalstudydatarequest.com</ipd_description>
  </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/NCT03839823
org study id: CLEE011A3201C
nct id: NCT03839823
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
To compare the combination of Ribociclib plus goserelin acetate with hormonal therapy versus
      combination chemotherapy in premenopausal or perimenopausal patients with advanced or
      metastatic breast cancer
A phase II randomized study of the combination of Ribociclib plus goserelin acetate with
      Hormonal Therapy versus physician choice chemotherapy in premenopausal or perimenopausal
      patients with hormone receptor-positive/ HER2-negative inoperable locally advanced or
      metastatic breast cancer - RIGHT Choice Study
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a randomized, phase II, open label, multi-center trial comparing the combination of NSAI (letrozole or anastrozole) + goserelin + ribociclib versus combination chemotherapy (either of docetaxel/capecitabine or paclitaxel/gemcitabine or capecitabine/vinorelbine). Premenopausal or perimenopausal women with HR+, HER2- negative, advanced breast cancer with ECOG performance status of 0 to 2 and having symptomatic visceral metastases, or rapid progression of disease or impending visceral compromise, or markedly symptomatic non visceral disease will be considered for this study
primary purpose: Treatment
masking: None (Open Label)
measure: Progression Free Survival
time frame: Up to approximately 34 months
description: Progression-free survival is defined as the time from the date of randomization to the date of the first documented progression as per local review and according to RECIST 1.1 or death due to any cause.
measure: Time to treatment failure
time frame: Up to approximately 34 months
description: Time to treatment failure is defined as the time from the date of randomization/start of treatment to the earliest of date of progression, date of death due to any cause, change to other anti-cancer therapy, or date of discontinuation due to reasons other than 'Protocol violation' or 'Administrative problems'.
measure: Overall response rate (ORR)
time frame: Up to approximately 34 months
description: Overall response rate (ORR) is defined as the proportion of patients whose best overall response is either complete response (CR) or partial response (PR), as per local review and according to RECIST 1.1.
measure: Clinical benefit rate
time frame: Up to approximately 34 months
description: Clinical benefit rate is defined as the proportion of patients with a best overall response of CR, or PR or stable disease, lasting for a duration of at least 24 weeks, as defined by RECIST 1.1.
measure: Time to response
time frame: Up to approximately 34 months
description: Time to response is defined as the time from the date of randomization to the first documented response of either CR or PR, which must be subsequently confirmed, as defined by RECIST 1.1.
measure: Overall survival
time frame: Up to approximately 46 months
description: Overall survival is defined as the time from the date of randomization to the date of death due to any cause.
measure: Frequency/severity of adverse events, lab abnormalities.
time frame: Up to approximately 46 months
description: Safety of ribociclib in combination with NSAI and goserelin, and combination chemotherapies
measure: Change from baseline in the global health status/QOL scale score by using FACT-B questionnaire
time frame: Up to approximately 46 months
description: Functional Assessment of Cancer Therapy - Breast (FACT-B) will be collected to assess health-related QoL, health status, functioning, disease symptoms, side effects, and cancer-related pain.
Descriptive statistics will be used to summarize the overall score at each scheduled assessment time point. Additionally, change from baseline at the time of each assessment will be summarized.
The distribution of time to definitive 10% deterioration in the global health status from FACT-B questionnaire will be assessed in the two treatment arms. Scores range from 0 to 4. no subscale. 0 score is the worst for social/family and functional wellbeing and 4 is the worst for physical, emotional wellbeing and additional concerns.
measure: 3-month treatment failure rate
time frame: Up to approximately 34 months
description: Treatment failure rate is defined as the proportion of patients who discontinued the study treatment due to progressive disease, death due to any cause, change to other anti-cancer therapy, or discontinuation due to reasons other than protocol violation or administrative problems.
arm group label: Comparator arm
arm group type: Active Comparator
description: Combination chemotherapies of docetaxel/capecitabine, paclitaxel/gemcitabine or capecitabine/vinorelbine will be administer to patients enrolled in the control group. The chemotherapy regimen will be decided by the treating physician.
arm group label: Ribociclib arm
arm group type: Experimental
description: Combination of non-steroidal aromatase inhibitor: NSAI (letrozole or anastrozole) + goserelin + ribociclib.
Ribociclib (600 mg) is dosed orally for the first 21 days out of a 28 day cycle.
Letrozole (2.5 mg) or anastrozole (1 mg) are dosed orally daily (28 days out of the 28 day cycle).
Goserelin (3.6 mg) is continuously released via a subcutaneous implant injected on Day 1 of each 28 day cycle (regardless of ribociclib treatment cycle) with an administration window of + 3 days.
intervention type: Combination Product
intervention name: Docetaxel / Capecitabine
description: Docetaxel (IV Infusion) / Capecitabine (Tablets for oral use):
Docetaxel once, on day 1 of the 3-weeks cycle. Capecitabine twice daily, on Days 1 to 14, followed by a 1-week rest period, in 3 weeks cycle.
Docetaxel (60 - 75 mg/m²)/capecitabine (1600 - 2500 mg/m²/day)
arm group label: Comparator arm
other name: Combination chemotherapy group.
other name: The chemotherapy regimen will be decided by the treating physician.
intervention type: Combination Product
intervention name: Capecitabine / Vinorelbine
description: Capecitabine (Tablets for oral use) / Vinorelbine (Capsule for Oral use/IV infusion ).
Capecitabine twice daily on day 1 to 14, followed by a 1-week rest period, in 3 weeks cycle.
Vinorelbine, once, on Day 1 and Day 8 in 3 weeks cycles.
Capecitabine (1600 - 2500 mg/m2/day)/vinorelbine (60 to 80 mg/m2/day [oral] or (25 to 30 mg/m2 [IV infusion]
arm group label: Comparator arm
other name: Combination chemotherapy group.
other name: The chemotherapy regimen will be decided by the treating physician.
intervention type: Combination Product
intervention name: Paclitaxel / Gemcitabine
description: Paclitaxel (IV Infusion) / Gemcitabine (IV Infusion):
Paclitaxel via 3-hour intravenous (IV) infusion on Day 1 in 3-weeks cycles, OR Paclitaxel via 1 hour intravenous (IV) infusion on Day 1 and day 8- in 3-weeks cycles.
Gemcitabine at via 30 minute IV infusion on Day 1 and Day 8 in 3 weeks cycles.
Paclitaxel (175 mg/m2) (on Day 1 in 3-weeks cycles)/ gemcitabine (1000 - 1250 mg/m2)
OR
Paclitaxel (80 - 90 mg/m2) (on Day 1 and Day 8 in 3-weeks cycles) / gemcitabine (800 - 1250 mg/m2)
arm group label: Comparator arm
other name: Combination chemotherapy group.
other name: The chemotherapy regimen will be decided by the treating physician.
intervention type: Drug
intervention name: Ribociclib
description: Dose: 600 mg (200 mg * 3) Days 1 to 21 of each 28 day cycle Tablets for oral use
arm group label: Ribociclib arm
other name: Endocrine treatment arm:
other name: NSAI + goserelin+ ribociclib
intervention type: Drug
intervention name: Letrozole OR Anastrozole
description: Letrozole:
Dose: 2.5 mg All days of every cycle without interruption). Tablets for oral use
Anastrozole:
dose: 1 mg All days of every cycle without interruption. Tablets for oral use
The NSAI (letrozole or anastrozole) will be decided by the treating physician.
arm group label: Ribociclib arm
other name: Endocrine treatment arm:
other name: NSAI + goserelin+ ribociclib
intervention type: Drug
intervention name: Goserelin
description: Dose: 3.6 mg Day 1 of each 28 day cycle (regardless of ribociclib treatment cycle) with an administration window of + 3 days.
Subcutaneous implant
arm group label: Ribociclib arm
other name: Endocrine treatment arm:
other name: NSAI + goserelin+ ribociclib
criteria: 
gender: Female
gender based: Yes
gender description: Patient is an adult female ≥ 18 years old and < 60 years old at the time of informed consent.
minimum age: 18 Years
maximum age: 59 Years
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
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country: Egypt
country: India
country: Jordan
country: Lebanon
country: Malaysia
country: Russian Federation
country: Saudi Arabia
country: Singapore
country: South Africa
country: Taiwan
country: Thailand
country: Turkey
country: Vietnam
country: Philippines
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Paclitaxel
mesh term: Vinorelbine
mesh term: Docetaxel
mesh term: Gemcitabine
mesh term: Capecitabine
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 review 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 availability is according to the criteria and process described on www.clinicalstudydatarequest.com