<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/NCT03820986</url>
  </required_header>
  <id_info>
    <org_study_id>7902-003</org_study_id>
    <secondary_id>MK-7902-003</secondary_id>
    <secondary_id>E7080-G000-312</secondary_id>
    <secondary_id>LEAP-003</secondary_id>
    <secondary_id>2018-002520-16</secondary_id>
    <nct_id>NCT03820986</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy Study of Pembrolizumab (MK-3475) Combined With Lenvatinib (MK-7902/E7080) as First-line Intervention in Adults With Advance Melanoma (MK-7902-003/E7080-G000-312/LEAP-003)</brief_title>
  <official_title>A Phase 3 Randomized, Placebo-controlled Trial to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) and Lenvatinib (E7080/MK-7902) Versus Pembrolizumab Alone as First-line Intervention in Participants With Advanced Melanoma (LEAP-003)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eisai Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Merck Sharp &amp; Dohme LLC</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The purpose of this study is to assess the safety and efficacy of pembrolizumab (MK-3475)&#xD;
      combined with lenvatinib (MK-7902/E7080) compared to pembrolizumab alone (with placebo for&#xD;
      lenvatinib) as first-line treatment in adults with no prior systemic therapy for their&#xD;
      advanced melanoma.&#xD;
&#xD;
      The primary study hypotheses are that: 1) The combination of pembrolizumab and lenvatinib is&#xD;
      superior to pembrolizumab and placebo as assessed by Progression-free Survival (PFS) per&#xD;
      Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), and 2) The combination&#xD;
      of pembrolizumab and lenvatinib is superior to pembrolizumab and placebo as assessed by&#xD;
      Overall Survival (OS). For this study, RECIST 1.1 has been modified to follow a maximum of 10&#xD;
      target lesions and a maximum of 5 target lesions per organ.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      As of 03-April-2023 active participants, investigator, and sponsor personnel or delegate(s)&#xD;
      involved in the treatment administration or clinical evaluation of the participants will be&#xD;
      unblinded.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 12, 2019</start_date>
  <completion_date type="Anticipated">April 6, 2024</completion_date>
  <primary_completion_date type="Actual">January 18, 2023</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression-free Survival (PFS) as Assessed by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)</measure>
    <time_frame>Up to approximately 36 months</time_frame>
    <description>PFS is defined as the time from date of randomization to the date of the first documentation of progressive disease (PD) or death from any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions is also considered PD. For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. PFS as assessed by modified RECIST 1.1 will be presented.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Up to approximately 36 months</time_frame>
    <description>OS is defined as the time from date of randomization to date of death from any cause. OS will be presented.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) as Assessed by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)</measure>
    <time_frame>Up to approximately 36 months</time_frame>
    <description>ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. ORR as assessed by modified RECIST 1.1 will be presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR) as Assessed by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)</measure>
    <time_frame>Up to approximately 36 months</time_frame>
    <description>For participants who demonstrated CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), DOR is defined as the date of the first documented evidence of CR or PR until PD or death from any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions is also considered PD. For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. DOR as assessed by modified RECIST 1.1 will be presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Adverse Events (AEs)</measure>
    <time_frame>Up to approximately 40 months</time_frame>
    <description>An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Discontinue Study Treatment Due to Adverse Events (AEs)</measure>
    <time_frame>Up to approximately 24 months</time_frame>
    <description>The number of participants who discontinue study treatment due to an AE will be presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire-Core 30 [QLQ-C30] Global Health Status (GHS) Score</measure>
    <time_frame>Baseline (Cycle 1 Day 1: Predose) and at designated time points: Predose; each cycle is 21 days (Up to approximately 27 months)</time_frame>
    <description>The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The GHS Score consists of participant responses to questions regarding GHS (How would you rate your overall health during the past week?). For GHS, responses range in score from 0 to 100, with a higher score indicating a better outcome. The change from Baseline in GHS Score will be presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire-Core 30 [QLQ-C30] Physical Function (PF) Score</measure>
    <time_frame>Baseline (Cycle 1 Day 1: Predose) and at designated time points: Predose; each cycle is 21 days (Up to approximately 27 months)</time_frame>
    <description>The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The PF Score consists of participant responses to questions regarding PF (5 questions about daily activities [strenuous activities, long walks, short walks, bed/chair rest and needing help with eating, dressing, washing themselves or using the toilet]. For PF, responses range in score from 0 to 100, with a higher score indicating a better outcome. The change from Baseline in PF Score will be presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to True Deterioration (TTD) Based on Change from Baseline in European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire-Core 30 [QLQ-C30] in Global Health Status (GHS) Score</measure>
    <time_frame>Up to approximately 27 months</time_frame>
    <description>TTD is defined as the time from Baseline to 1st onset of a ≥10-point negative change (decrease) in EORTC-QLQ-C30 GHS Score. The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The GHS Score consists of participant responses to questions regarding GHS (How would you rate your overall health during the past week?). For GHS, responses range in score from 0 to 100, with a higher score indicating a better outcome. TTD, based on a ≥10-point negative change (decrease) from Baseline in GHS Score will be presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to True Deterioration (TTD) Based on Change from Baseline in European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire-Core 30 [QLQ-C30] in Physical Function (PF) Score</measure>
    <time_frame>Up to approximately 27 months</time_frame>
    <description>TTD is defined as the time from Baseline to 1st onset of a ≥10-point negative change (decrease) in EORTC-QLQ-C30 PF Score. The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The PF Score consists of participant responses to questions regarding PF (5 questions about daily activities [strenuous activities, long walks, short walks, bed/chair rest &amp; needing help with eating, dressing, washing themselves or using the toilet]. For PF, responses range in score from 0 to 100, with a higher score indicating a better outcome. TTD, based on a ≥10-point negative change (decrease) from Baseline in PF Score will be presented.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">674</enrollment>
  <condition>Malignant Melanoma</condition>
  <arm_group>
    <arm_group_label>Pembrolizumab+Lenvatinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule daily for up to at least 2 years.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pembrolizumab+Placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule daily for up to at least 2 years.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>IV infusion</description>
    <arm_group_label>Pembrolizumab+Lenvatinib</arm_group_label>
    <arm_group_label>Pembrolizumab+Placebo</arm_group_label>
    <other_name>MK-3475</other_name>
    <other_name>KEYTRUDA®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenvatinib</intervention_name>
    <description>Oral capsule</description>
    <arm_group_label>Pembrolizumab+Lenvatinib</arm_group_label>
    <other_name>MK-7902</other_name>
    <other_name>E7080</other_name>
    <other_name>LENVIMA®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo for lenvatinib</intervention_name>
    <description>Oral capsule</description>
    <arm_group_label>Pembrolizumab+Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Has histologically or cytologically confirmed melanoma.&#xD;
&#xD;
          -  Has unresectable Stage III or Stage IV melanoma, as per American Joint Committee on&#xD;
             Cancer guidelines, not amenable to local therapy.&#xD;
&#xD;
          -  Has been untreated for advanced or metastatic disease except as follows:&#xD;
&#xD;
               1. Proto-oncogene B-Raf (BRAF) V600 mutation-positive melanoma may have received&#xD;
                  standard of care targeted therapy as first-line therapy for advanced or&#xD;
                  metastatic disease. Participants that do not have a BRAF V600 mutation but did&#xD;
                  receive BRAF or BRAF/MEKi therapy are eligible to participate in this study after&#xD;
                  discussion with the medical monitor.&#xD;
&#xD;
               2. Prior adjuvant or neoadjuvant therapy, with targeted therapy or immunotherapy&#xD;
                  (such as anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4],&#xD;
                  anti-programmed cell death 1 [anti-PD-1] therapy or interferon) will only be&#xD;
                  permitted if relapse did not occur during active treatment or within 6 months of&#xD;
                  treatment discontinuation.&#xD;
&#xD;
          -  Have documentation of BRAF V600-activating mutation status or consent to BRAF V600&#xD;
             mutation testing during the Screening period (participants with BRAF mutation-positive&#xD;
             melanoma as well as BRAF wild-type or unknown are eligible).&#xD;
&#xD;
          -  Has an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.&#xD;
&#xD;
          -  Has the presence of ≥1 measurable lesion by computed tomography (CT) or magnetic&#xD;
             resonance imaging (MRI) per RECIST 1.1.&#xD;
&#xD;
          -  Provides a tumor biopsy. Participants must submit tumor sample during Screening for&#xD;
             confirmation of adequacy of tumor tissue at a central pathology laboratory.&#xD;
             Participants who do not submit a tumor tissue sample will not be randomized. The tumor&#xD;
             biopsy may not be obtained from a lone target lesion. Confirmation of presence of&#xD;
             tumor tissue is not required prior to randomization.&#xD;
&#xD;
          -  Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less&#xD;
             (except alopecia). If participant received major surgery or radiation therapy of &gt;30&#xD;
             Gray (Gy), they must have recovered from the toxicity and/or complications from the&#xD;
             intervention.&#xD;
&#xD;
          -  Male participants must agree to use contraception during the treatment period and for&#xD;
             at least 7 days after the last dose of study treatment and refrain from donating sperm&#xD;
             during this period. Please note that 7 days after lenvatinib/placebo is stopped, if&#xD;
             the participant is on pembrolizumab only, no male contraception measures are needed.&#xD;
             Contraception use by men should be consistent with local regulations regarding the&#xD;
             methods of contraception for those participating in clinical studies. If the&#xD;
             contraception requirements in the local label for any of the study interventions is&#xD;
             more stringent than the requirements above, the local label requirements are to be&#xD;
             followed.&#xD;
&#xD;
          -  Female participants must not be pregnant, not breastfeeding, and ≥1 of the following&#xD;
             conditions applies:&#xD;
&#xD;
               1. Not a woman of childbearing potential (WOCBP). OR&#xD;
&#xD;
               2. A WOCBP who agrees to use study-approved contraception during the treatment&#xD;
                  period and for at least 120 days after the last dose of study treatment.&#xD;
&#xD;
          -  The participant (or legally acceptable representative) has provided documented&#xD;
             informed consent for the study.&#xD;
&#xD;
          -  Has adequately controlled blood pressure (BP) with or without antihypertensive&#xD;
             medications, defined as BP ≤150/90 mmHg at screening and no change in antihypertensive&#xD;
             medications within 1 week before Cycle 1 Day 1.&#xD;
&#xD;
          -  Has adequate organ function.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy&#xD;
             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of&#xD;
             immunosuppressive therapy within 7 days before the first dose of study treatment.&#xD;
&#xD;
          -  Has a known additional malignancy that is progressing or requires active treatment.&#xD;
             Exceptions include early stage cancers (carcinoma in situ or Stage 1, non-ulcerated&#xD;
             primary melanoma &lt;1 mm in depth with no nodal involvement) treated with curative&#xD;
             intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ&#xD;
             cervical cancer, or in situ breast cancer that has undergone potentially curative&#xD;
             therapy.&#xD;
&#xD;
          -  Has known active central nervous system metastases and/or carcinomatous meningitis.&#xD;
&#xD;
          -  Has ocular melanoma.&#xD;
&#xD;
          -  Has known hypersensitivity to active substances or any of their excipients including&#xD;
             previous clinically significant hypersensitivity reaction to treatment with another&#xD;
             monoclonal antibody.&#xD;
&#xD;
          -  Has an active autoimmune disease that has required systemic treatment in past 2 years&#xD;
             (i.e., with use of disease-modifying agents, corticosteroids or immunosuppressive&#xD;
             drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid&#xD;
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a&#xD;
             form of systemic treatment.&#xD;
&#xD;
          -  Has an active infection requiring systemic therapy.&#xD;
&#xD;
          -  Has known history of human immunodeficiency virus (HIV) infection&#xD;
&#xD;
          -  Has known history of or is positive for hepatitis B virus or hepatitis C virus&#xD;
             infection.&#xD;
&#xD;
          -  Has a history of (non-infectious) pneumonitis/interstitial lung disease that required&#xD;
             steroids or has current pneumonitis/interstitial lung disease.&#xD;
&#xD;
          -  Has a history of active tuberculosis (Bacillus tuberculosis).&#xD;
&#xD;
          -  Gastrointestinal malabsorption or any other condition that might affect the absorption&#xD;
             of lenvatinib.&#xD;
&#xD;
          -  Has had a major surgery within 3 weeks prior to first dose of study intervention.&#xD;
             Note: Adequate wound healing after major surgery must be assessed clinically&#xD;
             independent of time elapsed for eligibility.&#xD;
&#xD;
          -  Has a preexisting Grade ≥3 gastrointestinal or non-gastrointestinal fistula.&#xD;
&#xD;
          -  Has radiographic evidence of encasement or invasion of major blood vessel, or of&#xD;
             intratumoral cavitation.&#xD;
&#xD;
          -  Has active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior&#xD;
             to the first dose of study treatment.&#xD;
&#xD;
          -  Has clinically significant cardiovascular disease from 12 months of the first dose of&#xD;
             study treatment including New York Heart Association Class III or IV congestive heart&#xD;
             failure, unstable angina, myocardial infarction, cerebral vascular accident, or&#xD;
             cardiac arrhythmia associated with hemodynamic instability.&#xD;
&#xD;
          -  Has urine protein ≥1 g/24-hour. Note: Participants with ≥2+ (≥100 mg/dL) proteinuria&#xD;
             on urine dipstick testing (or urinalysis) will undergo 24-hour urine collection for&#xD;
             quantitative assessment of proteinuria.&#xD;
&#xD;
          -  Prolongation of QTcF interval to &gt;480 ms. Note: If the QTcF is prolonged to &gt;480 ms in&#xD;
             the presence of a pacemaker, contact the Sponsor to determine eligibility.&#xD;
&#xD;
          -  Has left ventricular ejection fraction (LVEF) below the institutional (or local&#xD;
             laboratory) normal range, as determined by multigated acquisition scan (MUGA) or&#xD;
             echocardiogram.&#xD;
&#xD;
          -  Has received prior therapy in the adjuvant setting. Note: Targeted therapy,&#xD;
             anti-CTLA-4, or anti-PD-1 may be allowed.&#xD;
&#xD;
          -  Has received prior systemic treatment for unresectable or metastatic melanoma other&#xD;
             than targeted therapy as noted in Inclusion Criteria above&#xD;
&#xD;
          -  Has received prior therapy with a monoclonal antibody, chemotherapy, or an&#xD;
             investigational agent or device within 4 weeks or 5 half-lives (whichever is longer)&#xD;
             before administration of study treatment or not recovered (≤Grade 1 or at Baseline)&#xD;
             from adverse events due to previously administered agents.&#xD;
&#xD;
        Exception to this rule would be use of denosumab, which is not excluded. Note: Participants&#xD;
        with alopecia and ≤Grade 2 neuropathy are an exception and may enroll.&#xD;
&#xD;
          -  Has received prior radiotherapy within 2 weeks of first dose of study treatment (Cycle&#xD;
             1 Day 1). Participants must have recovered from all radiation-related toxicities, not&#xD;
             require corticosteroids, and not have had radiation pneumonitis.&#xD;
&#xD;
          -  Has received live vaccine within 30 days before the first dose of study treatment.&#xD;
&#xD;
          -  Is currently participating in or has participated in a study of an investigational&#xD;
             agent or has used an investigational device within 4 weeks prior to the first dose of&#xD;
             study treatment.&#xD;
&#xD;
          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality&#xD;
             that might confound the results of the study, interfere with the participant's&#xD;
             participation for the full duration of the study, or is not in the best interest of&#xD;
             the participant to participate, in the opinion of the treating investigator.&#xD;
&#xD;
          -  Has had an allogeneic tissue/solid organ transplant.&#xD;
&#xD;
          -  Has a known psychiatric or substance abuse disorder that would interfere with&#xD;
             cooperation with the requirements of the study.&#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>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Merck Sharp &amp; Dohme LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Angeles Clinic and Research Institute ( Site 0707)</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90025</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCSF Helen Diller Family Comprehensive Cancer Center ( Site 0704)</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>California Pacific Medical Center Research Institute ( Site 0705)</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John Wayne Cancer Institute ( Site 0706)</name>
      <address>
        <city>Santa Monica</city>
        <state>California</state>
        <zip>90404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Cancer Center ( Site 0708)</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale Cancer Center ( Site 0709)</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baptist MD Anderson Cancer Center ( Site 0767)</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mid-Florida Cancer Centers ( Site 0764)</name>
      <address>
        <city>Orange City</city>
        <state>Florida</state>
        <zip>32763</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AMG Oncology ( Site 0714)</name>
      <address>
        <city>Park Ridge</city>
        <state>Illinois</state>
        <zip>60068</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois Cancer Care, PC ( Site 0765)</name>
      <address>
        <city>Peoria</city>
        <state>Illinois</state>
        <zip>61615</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Minnesota Oncology Specialist, PA ( Site 0766)</name>
      <address>
        <city>Fridley</city>
        <state>Minnesota</state>
        <zip>55432</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Vincent Frontier Cancer Center ( Site 0724)</name>
      <address>
        <city>Billings</city>
        <state>Montana</state>
        <zip>59102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Atlantic Health System ( Site 0768)</name>
      <address>
        <city>Morristown</city>
        <state>New Jersey</state>
        <zip>07960</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Valley Hospital ( Site 0749)</name>
      <address>
        <city>Paramus</city>
        <state>New Jersey</state>
        <zip>07652</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of North Carolina - Cancer Hospital ( Site 0751)</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27514</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OHSU Center for Health &amp; Healing ( Site 0731)</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inova Schar Cancer Institute ( Site 0739)</name>
      <address>
        <city>Fairfax</city>
        <state>Virginia</state>
        <zip>22031-4867</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lismore Base Hospital ( Site 0453)</name>
      <address>
        <city>Lismore</city>
        <state>Australian Capital Territory</state>
        <zip>2480</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Melanoma Institute Australia ( Site 0452)</name>
      <address>
        <city>North Sydney</city>
        <state>New South Wales</state>
        <zip>2060</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Westmead Hospital ( Site 0451)</name>
      <address>
        <city>Westmead</city>
        <state>New South Wales</state>
        <zip>2145</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Alexandra Hospital ( Site 0454)</name>
      <address>
        <city>Wooloongabba</city>
        <state>Queensland</state>
        <zip>4102</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eastern Health ( Site 0457)</name>
      <address>
        <city>Box Hill</city>
        <state>Victoria</state>
        <zip>3128</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fiona Stanley Hospital ( Site 0456)</name>
      <address>
        <city>Murdoch</city>
        <state>Western Australia</state>
        <zip>6150</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LKH Universitatsklinikum Graz ( Site 0776)</name>
      <address>
        <city>Graz</city>
        <state>Steiermark</state>
        <zip>8036</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Universitat Wien ( Site 0778)</name>
      <address>
        <city>Wien</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PERSONAL - Oncologia de Precisao e Personalizada ( Site 0399)</name>
      <address>
        <city>Belo Horizonte</city>
        <state>Minas Gerais</state>
        <zip>30130-090</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Caridade de Ijui ( Site 0391)</name>
      <address>
        <city>Ijui</city>
        <state>Rio Grande Do Sul</state>
        <zip>98700-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Sao Vicente de Paulo ( Site 0396)</name>
      <address>
        <city>Passo Fundo</city>
        <state>Rio Grande Do Sul</state>
        <zip>99010-080</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 0397)</name>
      <address>
        <city>Porto Alegre</city>
        <state>Rio Grande Do Sul</state>
        <zip>90610-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Nacional de Cancer Hospital do Cancer II ( Site 0394)</name>
      <address>
        <city>Rio de Janeiro</city>
        <zip>20220-410</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>BC Cancer-Kelowna - Sindi Ahluwalia Hawkins Centre ( Site 0661)</name>
      <address>
        <city>Kelowna</city>
        <state>British Columbia</state>
        <zip>V1Y 5L3</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lions Gate Hospital ( Site 0662)</name>
      <address>
        <city>North Vancouver</city>
        <state>British Columbia</state>
        <zip>V7L 2L7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sunnybrook Research Institute ( Site 0654)</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4N 3M5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0652)</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H2W 3E4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McGill University Health Centre ( Site 0651)</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H4A 3J1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Investigación del Cáncer James Lind ( Site 0425)</name>
      <address>
        <city>Temuco</city>
        <state>Araucania</state>
        <zip>4780000</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundacion Arturo Lopez Perez FALP ( Site 0421)</name>
      <address>
        <city>Santiago</city>
        <state>Region M. De Santiago</state>
        <zip>7500921</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pontificia Universidad Catolica de Chile ( Site 0422)</name>
      <address>
        <city>Santiago</city>
        <state>Region M. De Santiago</state>
        <zip>8330024</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sociedad Medica Aren y Bachero Limitada ( Site 0426)</name>
      <address>
        <city>Santiago</city>
        <state>Region M. De Santiago</state>
        <zip>8420383</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncocentro ( Site 0424)</name>
      <address>
        <city>Vina del Mar</city>
        <state>Valparaiso</state>
        <zip>2520598</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beijing Cancer Hospital ( Site 0601)</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100036</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fujian Provincial Cancer Hospital ( Site 0612)</name>
      <address>
        <city>Fuzhou</city>
        <state>Fujian</state>
        <zip>350014</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sun Yat-Sen University Cancer Center ( Site 0602)</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henan Cancer Hospital ( Site 0610)</name>
      <address>
        <city>Zhengzhou</city>
        <state>Henan</state>
        <zip>450003</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nanjing Drum Tower Hospital ( Site 0609)</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <zip>210008</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Hospital Of Jilin University ( Site 0603)</name>
      <address>
        <city>Chang Chun</city>
        <state>Jilin</state>
        <zip>130021</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fudan University Shanghai Cancer Center ( Site 0607)</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tianjin Medical University Cancer Institute &amp; Hospital ( Site 0606)</name>
      <address>
        <city>Tianjin</city>
        <state>Tianjin</state>
        <zip>300060</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yunnan Cancer Hospital ( Site 0604)</name>
      <address>
        <city>Kunming</city>
        <state>Yunnan</state>
        <zip>430030</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sir Run Run Shaw Hospital ( Site 0605)</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <zip>310018</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zhejiang Cancer Hospital ( Site 0608)</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <zip>310022</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital ARCHET 2 ( Site 0009)</name>
      <address>
        <city>Nice</city>
        <state>Alpes-Maritimes</state>
        <zip>06200</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital La Timone ( Site 0002)</name>
      <address>
        <city>Marseille</city>
        <state>Bouches-du-Rhone</state>
        <zip>13385</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Dijon Bourgogne ( Site 0010)</name>
      <address>
        <city>Dijon</city>
        <state>Cote-d Or</state>
        <zip>21079</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Claudius Regaud IUCT Oncopole ( Site 0003)</name>
      <address>
        <city>Toulouse</city>
        <state>Haute-Garonne</state>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Ambroise Pare Boulogne ( Site 0007)</name>
      <address>
        <city>Boulogne-Billancourt</city>
        <state>Hauts-de-Seine</state>
        <zip>92100</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRU Lille - Hopital Claude Huriez ( Site 0004)</name>
      <address>
        <city>Lille</city>
        <state>Nord</state>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Rouen ( Site 0013)</name>
      <address>
        <city>Rouen</city>
        <state>Seine-Maritime</state>
        <zip>76000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Victor Dupouy ( Site 0012)</name>
      <address>
        <city>Argenteuil</city>
        <state>Val-d Oise</state>
        <zip>95100</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy ( Site 0001)</name>
      <address>
        <city>Villejuif</city>
        <state>Val-de-Marne</state>
        <zip>94805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de la Miletrie Poitiers ( Site 0011)</name>
      <address>
        <city>Poitiers</city>
        <state>Vienne</state>
        <zip>86021</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinik fur Dermatologie Allergologie und Venerologie ( Site 0035)</name>
      <address>
        <city>Hannover</city>
        <state>Baden-Wurttemberg</state>
        <zip>30625</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Erlangen ( Site 0044)</name>
      <address>
        <city>Erlangen</city>
        <state>Bayern</state>
        <zip>91054</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Wuerzburg-Department of Dermatology ( Site 0036)</name>
      <address>
        <city>Wuerzburg</city>
        <state>Bayern</state>
        <zip>97080</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hautkrebszentrum Buxtehude ( Site 0037)</name>
      <address>
        <city>Buxtehude</city>
        <state>Niedersachsen</state>
        <zip>21614</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Carl Gustav Carus ( Site 0041)</name>
      <address>
        <city>Dresden</city>
        <state>Sachsen</state>
        <zip>01307</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Leipzig ( Site 0040)</name>
      <address>
        <city>Leipzig</city>
        <state>Sachsen</state>
        <zip>04103</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Schleswig-Holstein Campus Kiel ( Site 0033)</name>
      <address>
        <city>Kiel</city>
        <state>Schleswig-Holstein</state>
        <zip>24105</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SRH Wald-Klinikum Gera GmbH ( Site 0042)</name>
      <address>
        <city>Gera</city>
        <state>Thuringen</state>
        <zip>07548</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HaEmek Medical Center ( Site 0306)</name>
      <address>
        <city>Afula</city>
        <zip>1834111</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Soroka Medical Center ( Site 0303)</name>
      <address>
        <city>Beer Sheva</city>
        <zip>8457108</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rambam Medical Center ( Site 0301)</name>
      <address>
        <city>Haifa</city>
        <zip>3109601</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hadassah Ein Karem Hebrew University Medical Center ( Site 0305)</name>
      <address>
        <city>Jerusalem</city>
        <zip>9112001</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rabin Medical Center ( Site 0302)</name>
      <address>
        <city>Petah Tikva</city>
        <zip>4941492</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chaim Sheba Medical Center ( Site 0304)</name>
      <address>
        <city>Ramat Gan</city>
        <zip>5262000</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sourasky Medical Center ( Site 0307)</name>
      <address>
        <city>Tel Aviv</city>
        <zip>6423906</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shamir Medical Center-Assaf Harofeh ( Site 0308)</name>
      <address>
        <city>Zerifin</city>
        <zip>70300</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ASST Papa Giovanni XXIII ( Site 0062)</name>
      <address>
        <city>Bergamo</city>
        <state>Abruzzo</state>
        <zip>24127</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria Senese ( Site 0065)</name>
      <address>
        <city>Siena</city>
        <state>Toscana</state>
        <zip>53100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0064)</name>
      <address>
        <city>Milano</city>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Europeo di Oncologia ( Site 0067)</name>
      <address>
        <city>Milano</city>
        <zip>20141</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Nazionale Tumori Fondazione Pascale ( Site 0061)</name>
      <address>
        <city>Napoli</city>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Oncologico Veneto ( Site 0063)</name>
      <address>
        <city>Padova</city>
        <zip>35128</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kyungpook National University Chilgok Hospital ( Site 0553)</name>
      <address>
        <city>Daegu</city>
        <state>Taegu-Kwangyokshi</state>
        <zip>41404</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital ( Site 0554)</name>
      <address>
        <city>Seoul</city>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Severance Hospital Yonsei University Health System ( Site 0552)</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center ( Site 0551)</name>
      <address>
        <city>Seoul</city>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Onkologii im.prof. F. Lukaszczyka w Bydgoszczy ( Site 0273)</name>
      <address>
        <city>Bydgoszcz</city>
        <state>Kujawsko-pomorskie</state>
        <zip>85-796</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pratia MCM Krakow ( Site 0280)</name>
      <address>
        <city>Krakow</city>
        <state>Malopolskie</state>
        <zip>30-510</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uniwersyteckie Centrum Kliniczne ( Site 0281)</name>
      <address>
        <city>Gdansk</city>
        <state>Pomorskie</state>
        <zip>80-214</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 0278)</name>
      <address>
        <city>Gliwice</city>
        <state>Slaskie</state>
        <zip>44-102</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szpital Kliniczny im. Heliodora Swiecickiego Uniwers Medyczn ( Site 0272)</name>
      <address>
        <city>Poznan</city>
        <state>Wielkopolskie</state>
        <zip>60-780</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Care Langenhoven Drive Oncology Centre ( Site 0805)</name>
      <address>
        <city>Port Elizabeth</city>
        <state>Eastern Cape</state>
        <zip>6045</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sandton Oncology Medical Group PTY LTD ( Site 0802)</name>
      <address>
        <city>Johannesburg</city>
        <state>Gauteng</state>
        <zip>2196</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cape Town Oncology Trials Pty Ltd ( Site 0803)</name>
      <address>
        <city>Kraaifontein</city>
        <state>Western Cape</state>
        <zip>7570</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Duran i Reinals ICO de Hospitalet ( Site 0187)</name>
      <address>
        <city>Hospitalet del Llobregat</city>
        <state>Barcelona</state>
        <zip>08908</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Marques de Valdecilla ( Site 0181)</name>
      <address>
        <city>Santander</city>
        <state>Cantabria</state>
        <zip>39008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complejo Hospitalario Universitario A Coruna. CHUAC ( Site 0182)</name>
      <address>
        <city>A Coruna</city>
        <state>La Coruna</state>
        <zip>15006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Insular de Gran Canaria ( Site 0189)</name>
      <address>
        <city>Las Palmas de Gran Canaria</city>
        <state>Las Palmas</state>
        <zip>35001</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinic i Provincial Barcelona ( Site 0190)</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario Gregorio Maranon ( Site 0191)</name>
      <address>
        <city>Madrid</city>
        <zip>28009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Ramon y Cajal ( Site 0183)</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Paz ( Site 0184)</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Carlos Haya ( Site 0186)</name>
      <address>
        <city>Malaga</city>
        <zip>29010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Laenssjukhuset Ryhov ( Site 0215)</name>
      <address>
        <city>Jonkoping</city>
        <state>Jonkopings Lan</state>
        <zip>551 85</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrallasarettet Vaxjo ( Site 0214)</name>
      <address>
        <city>Vaxjo</city>
        <state>Kronobergs Lan</state>
        <zip>351 85</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Skanes Universitetssjukhus ( Site 0213)</name>
      <address>
        <city>Lund</city>
        <state>Skane Lan</state>
        <zip>221 85</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Karolinska Universitetssjukhuset ( Site 0211)</name>
      <address>
        <city>Solna</city>
        <state>Stockholms Lan</state>
        <zip>171 64</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Akademiska Sjukhuset ( Site 0218)</name>
      <address>
        <city>Uppsala</city>
        <state>Uppsala Lan</state>
        <zip>751 85</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norrlands Universitetssjukhus ( Site 0216)</name>
      <address>
        <city>Umea</city>
        <state>Vasterbottens Lan</state>
        <zip>901 85</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sahlgrenska Universitetssjukhuset ( Site 0212)</name>
      <address>
        <city>Goteborg</city>
        <state>Vastra Gotalands Lan</state>
        <zip>413 45</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsspital Basel ( Site 0094)</name>
      <address>
        <city>Basel</city>
        <state>Basel-Stadt</state>
        <zip>4031</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kantonsspital Graubuenden ( Site 0091)</name>
      <address>
        <city>Chur</city>
        <state>Grisons</state>
        <zip>7000</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kantonsspital Winterthur ( Site 0095)</name>
      <address>
        <city>Winterthur</city>
        <state>Zurich</state>
        <zip>8401</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsspital Zuerich ( Site 0092)</name>
      <address>
        <city>Zuerich-Flughafen</city>
        <state>Zurich</state>
        <zip>8058</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Western General Hospital ( Site 0121)</name>
      <address>
        <city>Edinburgh</city>
        <state>Edinburgh, City Of</state>
        <zip>EH4 2XU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guys and St Thomas NHS Foundation Trust ( Site 0126)</name>
      <address>
        <city>London</city>
        <state>London, City Of</state>
        <zip>SE1 9RT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Derriford Hospital ( Site 0129)</name>
      <address>
        <city>Plymouth</city>
        <zip>PL6 8DH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Singleton Hospital ( Site 0131)</name>
      <address>
        <city>Swansea</city>
        <zip>SA2 8QA</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Austria</country>
    <country>Brazil</country>
    <country>Canada</country>
    <country>Chile</country>
    <country>China</country>
    <country>France</country>
    <country>Germany</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Korea, Republic of</country>
    <country>Poland</country>
    <country>South Africa</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>Switzerland</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://merckoncologyclinicaltrials.com</url>
    <description>Merck Oncology Clinical Trial Information</description>
  </link>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>January 22, 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>April 24, 2023</last_update_submitted>
  <last_update_submitted_qc>April 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>programmed cell death 1 (PD-1, PD1)</keyword>
  <keyword>programmed cell death-ligand 1 (PD-L1, PDL1)</keyword>
  <keyword>programmed cell death-ligand 2 (PD-L2, PDL2)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
    <mesh_term>Lenvatinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf</ipd_description>
    <ipd_url>http://engagezone.msd.com/ds_documentation.php</ipd_url>
  </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/NCT03820986
org study id: 7902-003
secondary id: MK-7902-003
secondary id: E7080-G000-312
secondary id: LEAP-003
secondary id: 2018-002520-16
nct id: NCT03820986
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to assess the safety and efficacy of pembrolizumab (MK-3475)
      combined with lenvatinib (MK-7902/E7080) compared to pembrolizumab alone (with placebo for
      lenvatinib) as first-line treatment in adults with no prior systemic therapy for their
      advanced melanoma.

      The primary study hypotheses are that: 1) The combination of pembrolizumab and lenvatinib is
      superior to pembrolizumab and placebo as assessed by Progression-free Survival (PFS) per
      Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), and 2) The combination
      of pembrolizumab and lenvatinib is superior to pembrolizumab and placebo as assessed by
      Overall Survival (OS). For this study, RECIST 1.1 has been modified to follow a maximum of 10
      target lesions and a maximum of 5 target lesions per organ.
As of 03-April-2023 active participants, investigator, and sponsor personnel or delegate(s)
      involved in the treatment administration or clinical evaluation of the participants will be
      unblinded.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Progression-free Survival (PFS) as Assessed by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
time frame: Up to approximately 36 months
description: PFS is defined as the time from date of randomization to the date of the first documentation of progressive disease (PD) or death from any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions is also considered PD. For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. PFS as assessed by modified RECIST 1.1 will be presented.
measure: Overall Survival (OS)
time frame: Up to approximately 36 months
description: OS is defined as the time from date of randomization to date of death from any cause. OS will be presented.
measure: Objective Response Rate (ORR) as Assessed by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
time frame: Up to approximately 36 months
description: ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. ORR as assessed by modified RECIST 1.1 will be presented.
measure: Duration of Response (DOR) as Assessed by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
time frame: Up to approximately 36 months
description: For participants who demonstrated CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), DOR is defined as the date of the first documented evidence of CR or PR until PD or death from any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions is also considered PD. For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. DOR as assessed by modified RECIST 1.1 will be presented.
measure: Number of Participants with Adverse Events (AEs)
time frame: Up to approximately 40 months
description: An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be presented.
measure: Number of Participants Who Discontinue Study Treatment Due to Adverse Events (AEs)
time frame: Up to approximately 24 months
description: The number of participants who discontinue study treatment due to an AE will be presented.
measure: Change from Baseline in European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire-Core 30 [QLQ-C30] Global Health Status (GHS) Score
time frame: Baseline (Cycle 1 Day 1: Predose) and at designated time points: Predose; each cycle is 21 days (Up to approximately 27 months)
description: The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The GHS Score consists of participant responses to questions regarding GHS (How would you rate your overall health during the past week?). For GHS, responses range in score from 0 to 100, with a higher score indicating a better outcome. The change from Baseline in GHS Score will be presented.
measure: Change from Baseline in European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire-Core 30 [QLQ-C30] Physical Function (PF) Score
time frame: Baseline (Cycle 1 Day 1: Predose) and at designated time points: Predose; each cycle is 21 days (Up to approximately 27 months)
description: The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The PF Score consists of participant responses to questions regarding PF (5 questions about daily activities [strenuous activities, long walks, short walks, bed/chair rest and needing help with eating, dressing, washing themselves or using the toilet]. For PF, responses range in score from 0 to 100, with a higher score indicating a better outcome. The change from Baseline in PF Score will be presented.
measure: Time to True Deterioration (TTD) Based on Change from Baseline in European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire-Core 30 [QLQ-C30] in Global Health Status (GHS) Score
time frame: Up to approximately 27 months
description: TTD is defined as the time from Baseline to 1st onset of a ≥10-point negative change (decrease) in EORTC-QLQ-C30 GHS Score. The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The GHS Score consists of participant responses to questions regarding GHS (How would you rate your overall health during the past week?). For GHS, responses range in score from 0 to 100, with a higher score indicating a better outcome. TTD, based on a ≥10-point negative change (decrease) from Baseline in GHS Score will be presented.
measure: Time to True Deterioration (TTD) Based on Change from Baseline in European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire-Core 30 [QLQ-C30] in Physical Function (PF) Score
time frame: Up to approximately 27 months
description: TTD is defined as the time from Baseline to 1st onset of a ≥10-point negative change (decrease) in EORTC-QLQ-C30 PF Score. The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The PF Score consists of participant responses to questions regarding PF (5 questions about daily activities [strenuous activities, long walks, short walks, bed/chair rest & needing help with eating, dressing, washing themselves or using the toilet]. For PF, responses range in score from 0 to 100, with a higher score indicating a better outcome. TTD, based on a ≥10-point negative change (decrease) from Baseline in PF Score will be presented.
arm group label: Pembrolizumab+Lenvatinib
arm group type: Experimental
description: Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule daily for up to at least 2 years.
arm group label: Pembrolizumab+Placebo
arm group type: Active Comparator
description: Participants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule daily for up to at least 2 years.
intervention type: Biological
intervention name: Pembrolizumab
description: IV infusion
arm group label: Pembrolizumab+Lenvatinib
arm group label: Pembrolizumab+Placebo
other name: MK-3475
other name: KEYTRUDA®
intervention type: Drug
intervention name: Lenvatinib
description: Oral capsule
arm group label: Pembrolizumab+Lenvatinib
other name: MK-7902
other name: E7080
other name: LENVIMA®
intervention type: Drug
intervention name: Placebo for lenvatinib
description: Oral capsule
arm group label: Pembrolizumab+Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Merck Sharp & Dohme LLC
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country: Australia
country: Austria
country: Brazil
country: Canada
country: Chile
country: China
country: France
country: Germany
country: Israel
country: Italy
country: Korea, Republic of
country: Poland
country: South Africa
country: Spain
country: Sweden
country: Switzerland
country: United Kingdom
country: United States
url: http://merckoncologyclinicaltrials.com
description: Merck Oncology Clinical Trial Information
responsible party type: Sponsor
mesh term: Melanoma
mesh term: Pembrolizumab
mesh term: Lenvatinib
sharing ipd: Yes
ipd description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
ipd url: http://engagezone.msd.com/ds_documentation.php