<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/NCT01685060</url>
  </required_header>
  <id_info>
    <org_study_id>CLDK378A2201</org_study_id>
    <secondary_id>2012-003432-24</secondary_id>
    <nct_id>NCT01685060</nct_id>
  </id_info>
  <brief_title>LDK378 in Adult Patients With ALK-activated NSCLC Previously Treated With Chemotherapy and Crizotinib</brief_title>
  <official_title>A Phase II, Multicenter, Single-arm Study of Oral LDK378 in Adult Patients With ALK-activated Non-small Cell Lung Cancer Previously Treated With Chemotherapy and Crizotinib</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A single-arm, open-label, multicenter, phase II study. Treatment with LDK378 750 mg qd&#xD;
      continued until the patient experienced unacceptable toxicity that precluded further&#xD;
      treatment, discontinued treatment at the discretion of the investigator or patient, started a&#xD;
      new anti-cancer therapy and/or died. LDK378 could be continued beyond RECIST-defined&#xD;
      progressive disease (PD) as assessed by the investigator if, in the judgment of the&#xD;
      investigator, there was evidence of clinical benefit. In these patients tumor assessment&#xD;
      would continue as per the schedule of assessments until treatment with LDK378 was permanently&#xD;
      discontinued. Patients who discontinued the study medication in the absence of progression&#xD;
      continued to be followed for tumor assessment until the time of PD as assessed by the&#xD;
      investigator&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 26, 2012</start_date>
  <completion_date type="Actual">March 29, 2016</completion_date>
  <primary_completion_date type="Actual">March 29, 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Response Rate (ORR) to LDK378 Per Investigator Assessment</measure>
    <time_frame>6 cycles of 28 days up to 24 weeks</time_frame>
    <description>ORR per RECIST 1.1 calculated as the percentage of patients with a best overall confirmed response defined as complete response or partial response (CR+PR) as assessed by investigator. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to &lt; 10 mm 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>ORR Per Blinded Independent Review Committee (BIRC) Assessment</measure>
    <time_frame>6 cycles of 28 days up to 24 weeks</time_frame>
    <description>ORR (CR+PR) by BIRC is calculated as the percentage of patients with a best overall confirmed response defined as complete response or partial response (CR+PR) as assessed by BIRC. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to &lt; 10 mm 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR) by Investigator</measure>
    <time_frame>6 cycles of 28 days up to 24 weeks</time_frame>
    <description>DOR, calculated as the time from the date of the first confirmed CR or PR to the first documented progression or death due to any cause, by investigator. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to &lt; 10 mm 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR) by BIRC</measure>
    <time_frame>6 cycles of 28 days up to 24 weeks</time_frame>
    <description>DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or death due to underlying cancer, by BIRC (Blinded Imaging Review Committee). CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to &lt; 10 mm 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>6 cycles of 28 days up to 24 weeks</time_frame>
    <description>DCR was calculated as the percentage of patients with best overall response of CR, PR, SD, or non-CR non-PD (NCRNPD), per RECIST 1.1 by investigator. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to &lt; 10 mm 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. Non-CR/Non-PD (NCRNPD): refers to best overall responses that are neither CR nor PD per RECIST 1.1 criteria for patients with non-measurable disease only at baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Response (TTR) Per Investigator</measure>
    <time_frame>6 cycles of 28 days up to 24 weeks</time_frame>
    <description>TTR is the time from date of start of treatment to the first CR or PR observed which were confirmed afterwards.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Response (TTR) Per BIRC</measure>
    <time_frame>6 cycles of 28 days up to 24 weeks</time_frame>
    <description>TTR is the time from date of start of treatment to the first CR or PR observed which are confirmed afterwards.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS) Per Investigator</measure>
    <time_frame>6 cycles of 28 days up to 24 weeks</time_frame>
    <description>PFS, defined as the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient had no event or when the patient received any further anticancer therapy in the absence of disease progression, progression-free survival was censored at the date of last adequate tumor assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS) Per BIRC</measure>
    <time_frame>6 cycles of 28 days up to 24 weeks</time_frame>
    <description>PFS, defined as the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient had no event or when the patient received any further anticancer therapy in the absence of disease progression, progression-free survival was censored at the date of last adequate tumor assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Intracranial Response Rate (OIRR) Per Investigator</measure>
    <time_frame>6 cycles of 28 days up to 24 weeks</time_frame>
    <description>OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who had measureable disease in the brain at baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Intracranial Response Rate (OIRR) Per BIRC</measure>
    <time_frame>6 cycles of 28 days up to 24 weeks</time_frame>
    <description>OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who had measureable disease in the brain at baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>6 cycles of 28 days up to 24 weeks</time_frame>
    <description>OS, defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient was not known to have died, survival was censored at the date of last known date patient alive.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">140</enrollment>
  <condition>Non-Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>LDK378</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients treated with ceritinib/LDK378 750 mg once-daily, fasted</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LDK378</intervention_name>
    <description>Ceritinib/LDK378 was supplied as 150 mg hard gelatin capsules and were administered orally, once-daily at a dose of 750 mg on a continuous dosing schedule (5 x 150 mg capsules).</description>
    <arm_group_label>LDK378</arm_group_label>
    <other_name>Ceritinib</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion critieria:&#xD;
&#xD;
          -  Histologically or cytologically confirmed diagnosis of stage IIIB or IV NSCLC that&#xD;
             carries an ALK rearrangement, as per the FDA-approved FISH assay (Abbott Molecular&#xD;
             Inc.).&#xD;
&#xD;
          -  Age 18 years or older at the time of informed consent.&#xD;
&#xD;
          -  Patients must have NSCLC that has progressed during therapy with crizotinib or within&#xD;
             30 days of the last dose&#xD;
&#xD;
          -  Patients must have received 1-3 lines of cytotoxic chemotherapy (of which 1 must have&#xD;
             been a platinum doublet) to treat their locally advanced or metastatic NSCLC&#xD;
&#xD;
          -  Patients must have a tumor tissue sample available, collected either at the time of&#xD;
             diagnosis of NSCLC or any time since.&#xD;
&#xD;
          -  Patients must have recovered from all toxicities related to prior anticancer therapies&#xD;
             to grade ≤ 2, except for patients with grade 2 nausea/vomiting and/or grade 2 diarrhea&#xD;
             despite optimal supportive therapy who will not be allowed to participate in the&#xD;
             study.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Patients with known hypersensitivity to any of the excipients of LDK378.&#xD;
&#xD;
          -  Patients with symptomatic central nervous system (CNS) metastases who are&#xD;
             neurologically unstable or have required increasing doses of steroids within the 2&#xD;
             weeks prior to study entry to manage CNS symptoms.&#xD;
&#xD;
          -  History of carcinomatous meningitis.&#xD;
&#xD;
          -  Presence or history of a malignant disease other than NSCLC that has been diagnosed&#xD;
             and/or required therapy within the past 3 years.&#xD;
&#xD;
          -  Clinically significant, uncontrolled heart disease&#xD;
&#xD;
          -  Systemic anti-cancer therapy given after the last dose of crizotinib and prior to&#xD;
             starting study drug.&#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>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Highlands Oncology Group Dept of Highlands Oncology Grp</name>
      <address>
        <city>Fayetteville</city>
        <state>Arkansas</state>
        <zip>72703</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City of Hope National Medical Center Dept of Oncology 2</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010-3000</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California at Los Angeles Reg-5</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California at San Diego, Moores Cancer Ctr SC</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University Medical Center Stanford Cancer Center(2)</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Hospital SC</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University School of Medicine/Winship Cancer Institute Dept of Oncology</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago Medical Center SC</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Cancer Center DeptofUofKansas CancerCenter-2</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center of Kansas Dept of CCK</name>
      <address>
        <city>Wichita</city>
        <state>Kansas</state>
        <zip>67214-3728</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maryland Oncology Hematology, P.A. SC</name>
      <address>
        <city>Rockville</city>
        <state>Maryland</state>
        <zip>20850</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital Mass General</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Levine Cancer Institute SC 1</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute Drug Ship - 4</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>U of TX Southwestern Medical Center - SimmonsCompCancerCtr Clinical Research Office</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seattle Cancer Care Alliance SC-1</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin Univ Wisc 2</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 1Z2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Oshawa</city>
        <state>Ontario</state>
        <zip>L1G 2B9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Marseille cedex 20</city>
        <zip>13915</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Paris</city>
        <zip>75970</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Koeln</city>
        <state>Nordrhein-Westfalen</state>
        <zip>50937</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Heidelberg</city>
        <zip>69120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hong Kong</city>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Avellino</city>
        <state>AV</state>
        <zip>83100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Livorno</city>
        <state>LI</state>
        <zip>57124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Monza</city>
        <state>MB</state>
        <zip>20900</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Milano</city>
        <state>MI</state>
        <zip>20141</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Perugia</city>
        <state>PG</state>
        <zip>06129</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Parma</city>
        <state>PR</state>
        <zip>43100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Nagoya</city>
        <state>Aichi</state>
        <zip>464-8681</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kashiwa</city>
        <state>Chiba</state>
        <zip>277-8577</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Akashi</city>
        <state>Hyogo</state>
        <zip>673-8558</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Okayama-city</city>
        <state>Okayama</state>
        <zip>700-8558</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>OsakaSayama</city>
        <state>Osaka</state>
        <zip>589-8511</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sunto-gun</city>
        <state>Shizuoka</state>
        <zip>411-8777</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Chuo-ku</city>
        <state>Tokyo</state>
        <zip>104-0045</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Koto</city>
        <state>Tokyo</state>
        <zip>135-8550</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Fukuoka</city>
        <zip>811-1395</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Seoul</city>
        <state>Korea</state>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Seoul</city>
        <state>Korea</state>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Seoul</city>
        <state>Korea</state>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Amsterdam</city>
        <zip>1081 HV</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Groningen</city>
        <zip>9713 GZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Maastricht</city>
        <zip>5800</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Singapore</city>
        <zip>169610</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sevilla</city>
        <state>Andalucia</state>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Barcelona</city>
        <state>Catalunya</state>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>La Coruna</city>
        <state>Galicia</state>
        <zip>15006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>London</city>
        <zip>SE1 9RT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>France</country>
    <country>Germany</country>
    <country>Hong Kong</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Netherlands</country>
    <country>Singapore</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Sweden</country>
  </removed_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>September 4, 2012</study_first_submitted>
  <study_first_submitted_qc>September 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 13, 2012</study_first_posted>
  <results_first_submitted>March 27, 2017</results_first_submitted>
  <results_first_submitted_qc>March 27, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">May 8, 2017</results_first_posted>
  <last_update_submitted>May 25, 2017</last_update_submitted>
  <last_update_submitted_qc>May 25, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">June 19, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Non-Small Cell Lung Cancer</keyword>
  <keyword>NSCLC</keyword>
  <keyword>ALK</keyword>
  <keyword>LDK378</keyword>
  <keyword>Ceritinib</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ceritinib</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Approximately 137 patients were planned to be enrolled. A total of 140 patients were enrolled and treated with ceritinib.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>LDK378 750mg</title>
          <description>Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="140"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Entered Post-treatment Efficacy f/u</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Entered Survival Follow up</title>
              <participants_list>
                <participants group_id="P1" count="98"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Discontinued From Study</title>
              <participants_list>
                <participants group_id="P1" count="35"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="140"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Rollover patients</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progressive disease</title>
              <participants_list>
                <participants group_id="P1" count="69"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Subject/guardian decision</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Full Analysis Set (FAS) consisted of all patients who received at least one dose of ceritinib.</population>
      <group_list>
        <group group_id="B1">
          <title>LDK378 750mg</title>
          <description>Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="140"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="51.2" spread="11.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="70"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Overall Response Rate (ORR) to LDK378 Per Investigator Assessment</title>
        <description>ORR per RECIST 1.1 calculated as the percentage of patients with a best overall confirmed response defined as complete response or partial response (CR+PR) as assessed by investigator. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to &lt; 10 mm 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.</description>
        <time_frame>6 cycles of 28 days up to 24 weeks</time_frame>
        <population>Full Analysis Set (FAS) consisted of all patients who received at least one dose of ceritinib.</population>
        <group_list>
          <group group_id="O1">
            <title>LDK378 750mg</title>
            <description>Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate (ORR) to LDK378 Per Investigator Assessment</title>
          <description>ORR per RECIST 1.1 calculated as the percentage of patients with a best overall confirmed response defined as complete response or partial response (CR+PR) as assessed by investigator. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to &lt; 10 mm 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.</description>
          <population>Full Analysis Set (FAS) consisted of all patients who received at least one dose of ceritinib.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="140"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.7" lower_limit="32.5" upper_limit="49.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>ORR Per Blinded Independent Review Committee (BIRC) Assessment</title>
        <description>ORR (CR+PR) by BIRC is calculated as the percentage of patients with a best overall confirmed response defined as complete response or partial response (CR+PR) as assessed by BIRC. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to &lt; 10 mm 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.</description>
        <time_frame>6 cycles of 28 days up to 24 weeks</time_frame>
        <population>The Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib.</population>
        <group_list>
          <group group_id="O1">
            <title>LDK378 750mg</title>
            <description>Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.</description>
          </group>
        </group_list>
        <measure>
          <title>ORR Per Blinded Independent Review Committee (BIRC) Assessment</title>
          <description>ORR (CR+PR) by BIRC is calculated as the percentage of patients with a best overall confirmed response defined as complete response or partial response (CR+PR) as assessed by BIRC. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to &lt; 10 mm 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.</description>
          <population>The Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="140"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.7" lower_limit="27.8" upper_limit="44.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response (DOR) by Investigator</title>
        <description>DOR, calculated as the time from the date of the first confirmed CR or PR to the first documented progression or death due to any cause, by investigator. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to &lt; 10 mm 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.</description>
        <time_frame>6 cycles of 28 days up to 24 weeks</time_frame>
        <population>Full Analysis Set (FAS) consisted of all patients who received at least one dose of ceritinib. Only patients with confirmed complete response/partial response (CR/PR) per Investigator were included in this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>LDK378 750mg</title>
            <description>Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response (DOR) by Investigator</title>
          <description>DOR, calculated as the time from the date of the first confirmed CR or PR to the first documented progression or death due to any cause, by investigator. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to &lt; 10 mm 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.</description>
          <population>Full Analysis Set (FAS) consisted of all patients who received at least one dose of ceritinib. Only patients with confirmed complete response/partial response (CR/PR) per Investigator were included in this analysis.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.6" lower_limit="7.4" upper_limit="14.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response (DOR) by BIRC</title>
        <description>DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or death due to underlying cancer, by BIRC (Blinded Imaging Review Committee). CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to &lt; 10 mm 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.</description>
        <time_frame>6 cycles of 28 days up to 24 weeks</time_frame>
        <population>Full Analysis Set (FAS) consisted of all patients who received at least one dose of ceritinib. Only patients with confirmed complete response/partial response (CR/PR) per BIRC were included in this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>LDK378 750mg</title>
            <description>Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response (DOR) by BIRC</title>
          <description>DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or death due to underlying cancer, by BIRC (Blinded Imaging Review Committee). CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to &lt; 10 mm 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.</description>
          <population>Full Analysis Set (FAS) consisted of all patients who received at least one dose of ceritinib. Only patients with confirmed complete response/partial response (CR/PR) per BIRC were included in this analysis.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.9" lower_limit="9.3" upper_limit="18.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Disease Control Rate (DCR)</title>
        <description>DCR was calculated as the percentage of patients with best overall response of CR, PR, SD, or non-CR non-PD (NCRNPD), per RECIST 1.1 by investigator. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to &lt; 10 mm 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. Non-CR/Non-PD (NCRNPD): refers to best overall responses that are neither CR nor PD per RECIST 1.1 criteria for patients with non-measurable disease only at baseline.</description>
        <time_frame>6 cycles of 28 days up to 24 weeks</time_frame>
        <population>Full Analysis Set (FAS) consisted of all patients who received at least one dose of ceritinib.</population>
        <group_list>
          <group group_id="O1">
            <title>LDK378 750mg</title>
            <description>Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.</description>
          </group>
        </group_list>
        <measure>
          <title>Disease Control Rate (DCR)</title>
          <description>DCR was calculated as the percentage of patients with best overall response of CR, PR, SD, or non-CR non-PD (NCRNPD), per RECIST 1.1 by investigator. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to &lt; 10 mm 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. Non-CR/Non-PD (NCRNPD): refers to best overall responses that are neither CR nor PD per RECIST 1.1 criteria for patients with non-measurable disease only at baseline.</description>
          <population>Full Analysis Set (FAS) consisted of all patients who received at least one dose of ceritinib.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="140"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>DCR per Investigator</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="76.4" lower_limit="68.5" upper_limit="83.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DCR per BIRC</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80.0" lower_limit="72.4" upper_limit="86.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Response (TTR) Per Investigator</title>
        <description>TTR is the time from date of start of treatment to the first CR or PR observed which were confirmed afterwards.</description>
        <time_frame>6 cycles of 28 days up to 24 weeks</time_frame>
        <population>The Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib. Only patients with confirmed complete response/partial response (CR/PR) were included in this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>LDK378 750mg</title>
            <description>Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Response (TTR) Per Investigator</title>
          <description>TTR is the time from date of start of treatment to the first CR or PR observed which were confirmed afterwards.</description>
          <population>The Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib. Only patients with confirmed complete response/partial response (CR/PR) were included in this analysis.</population>
          <units>Months</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.0" spread="3.54" lower_limit="1.6" upper_limit="18.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Response (TTR) Per BIRC</title>
        <description>TTR is the time from date of start of treatment to the first CR or PR observed which are confirmed afterwards.</description>
        <time_frame>6 cycles of 28 days up to 24 weeks</time_frame>
        <population>The Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib. Only patients with confirmed complete response/partial response (CR/PR) were included in this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>LDK378 750mg</title>
            <description>Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Response (TTR) Per BIRC</title>
          <description>TTR is the time from date of start of treatment to the first CR or PR observed which are confirmed afterwards.</description>
          <population>The Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib. Only patients with confirmed complete response/partial response (CR/PR) were included in this analysis.</population>
          <units>Months</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.2" spread="1.44" lower_limit="1.6" upper_limit="10.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival (PFS) Per Investigator</title>
        <description>PFS, defined as the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient had no event or when the patient received any further anticancer therapy in the absence of disease progression, progression-free survival was censored at the date of last adequate tumor assessment.</description>
        <time_frame>6 cycles of 28 days up to 24 weeks</time_frame>
        <population>The Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib.</population>
        <group_list>
          <group group_id="O1">
            <title>LDK378 750mg</title>
            <description>Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival (PFS) Per Investigator</title>
          <description>PFS, defined as the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient had no event or when the patient received any further anticancer therapy in the absence of disease progression, progression-free survival was censored at the date of last adequate tumor assessment.</description>
          <population>The Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="140"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.8" lower_limit="5.4" upper_limit="7.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival (PFS) Per BIRC</title>
        <description>PFS, defined as the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient had no event or when the patient received any further anticancer therapy in the absence of disease progression, progression-free survival was censored at the date of last adequate tumor assessment.</description>
        <time_frame>6 cycles of 28 days up to 24 weeks</time_frame>
        <population>The Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib.</population>
        <group_list>
          <group group_id="O1">
            <title>LDK378 750mg</title>
            <description>Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival (PFS) Per BIRC</title>
          <description>PFS, defined as the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient had no event or when the patient received any further anticancer therapy in the absence of disease progression, progression-free survival was censored at the date of last adequate tumor assessment.</description>
          <population>The Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="140"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.4" lower_limit="5.6" upper_limit="10.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Intracranial Response Rate (OIRR) Per Investigator</title>
        <description>OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who had measureable disease in the brain at baseline.</description>
        <time_frame>6 cycles of 28 days up to 24 weeks</time_frame>
        <population>The Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib. Only patients with measurable disease in brain at baseline selected by Investigator were included in this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>LDK378 750mg</title>
            <description>Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Intracranial Response Rate (OIRR) Per Investigator</title>
          <description>OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who had measureable disease in the brain at baseline.</description>
          <population>The Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib. Only patients with measurable disease in brain at baseline selected by Investigator were included in this analysis.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.0" lower_limit="23.1" upper_limit="68.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Intracranial Response Rate (OIRR) Per BIRC</title>
        <description>OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who had measureable disease in the brain at baseline.</description>
        <time_frame>6 cycles of 28 days up to 24 weeks</time_frame>
        <population>The Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib. Only patients with measurable disease in brain at baseline selected by BIRC were included in this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>LDK378 750mg</title>
            <description>Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Intracranial Response Rate (OIRR) Per BIRC</title>
          <description>OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who had measureable disease in the brain at baseline.</description>
          <population>The Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib. Only patients with measurable disease in brain at baseline selected by BIRC were included in this analysis.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.7" lower_limit="18.6" upper_limit="55.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>OS, defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient was not known to have died, survival was censored at the date of last known date patient alive.</description>
        <time_frame>6 cycles of 28 days up to 24 weeks</time_frame>
        <population>Full Analysis Set (FAS) consisted of all patients who received at least one dose of ceritinib.</population>
        <group_list>
          <group group_id="O1">
            <title>LDK378 750mg</title>
            <description>Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>OS, defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient was not known to have died, survival was censored at the date of last known date patient alive.</description>
          <population>Full Analysis Set (FAS) consisted of all patients who received at least one dose of ceritinib.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="140"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.6" lower_limit="13.6" upper_limit="24.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Timeframe for AE</time_frame>
      <desc>AE additional description</desc>
      <group_list>
        <group group_id="E1">
          <title>LDK378 750 mg</title>
          <description>Patients treated with ceritinib/LDK378 750 mg once-daily, fasted.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (18.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="67" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>ANAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>FEBRILE NEUTROPENIA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>THROMBOCYTOPENIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>CORONARY ARTERY DISEASE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>PERICARDIAL EFFUSION</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>PERICARDITIS</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>ABDOMINAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>ASCITES</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>CONSTIPATION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>DYSPHAGIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>FAECALOMA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>GASTROINTESTINAL DISORDER</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>GASTROINTESTINAL TOXICITY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>INTESTINAL PERFORATION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>NAUSEA</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>PANCREATITIS</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>RETROPERITONEAL FIBROSIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>VOMITING</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>ASTHENIA</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>DISEASE PROGRESSION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>GENERAL PHYSICAL HEALTH DETERIORATION</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>MALAISE</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>NON-CARDIAC CHEST PAIN</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>PAIN</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>PYREXIA</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>HEPATIC FUNCTION ABNORMAL</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>HEPATOCELLULAR INJURY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>EMPYEMA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>ENTERITIS INFECTIOUS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>LUNG INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>MENINGITIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>PLEURAL INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>PNEUMONIA</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>RESPIRATORY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>SEPTIC SHOCK</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>URINARY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>VIRAL PERICARDITIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>HUMERUS FRACTURE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>PUBIS FRACTURE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>SPINAL COMPRESSION FRACTURE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>ALANINE AMINOTRANSFERASE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>ASPARTATE AMINOTRANSFERASE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>BLOOD CALCIUM INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>BLOOD CREATINE PHOSPHOKINASE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>BLOOD CREATININE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>WEIGHT DECREASED</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>DECREASED APPETITE</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>DEHYDRATION</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>DIABETES MELLITUS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>HYPERGLYCAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>BACK PAIN</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>BONE PAIN</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>NECK PAIN</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>COLON CANCER</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>METASTASES TO LIVER</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>METASTASES TO LUNG</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>METASTASES TO MENINGES</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>ALTERED STATE OF CONSCIOUSNESS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>APHASIA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>BRAIN OEDEMA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>CEREBROVASCULAR ACCIDENT</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>DYSARTHRIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>ENCEPHALOPATHY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>HEADACHE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>HEPATIC ENCEPHALOPATHY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>HYPERAESTHESIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>LETHARGY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>MOTOR DYSFUNCTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>PARAESTHESIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>PARAPARESIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>SEIZURE</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>SENSORY LOSS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>CONFUSIONAL STATE</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>HYDRONEPHROSIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>POLLAKIURIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>RENAL FAILURE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>RENAL IMPAIRMENT</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>COUGH</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>DYSPNOEA</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>LUNG DISORDER</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>PLEURAL EFFUSION</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>PLEURISY</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>PNEUMONITIS</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>PULMONARY EMBOLISM</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>PULMONARY HYPERTENSION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>RESPIRATORY FAILURE</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (18.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="139" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>ANAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>ABDOMINAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="45" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>ABDOMINAL PAIN UPPER</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>CONSTIPATION</sub_title>
                <counts group_id="E1" subjects_affected="42" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>DIARRHOEA</sub_title>
                <counts group_id="E1" subjects_affected="115" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>NAUSEA</sub_title>
                <counts group_id="E1" subjects_affected="115" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>STOMATITIS</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>VOMITING</sub_title>
                <counts group_id="E1" subjects_affected="92" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>ASTHENIA</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>FATIGUE</sub_title>
                <counts group_id="E1" subjects_affected="54" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>NON-CARDIAC CHEST PAIN</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>OEDEMA PERIPHERAL</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>PYREXIA</sub_title>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>NASOPHARYNGITIS</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>PNEUMONIA</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>UPPER RESPIRATORY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>ALANINE AMINOTRANSFERASE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="65" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>ASPARTATE AMINOTRANSFERASE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="55" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>BLOOD ALKALINE PHOSPHATASE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>BLOOD CREATININE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="27" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>ELECTROCARDIOGRAM QT PROLONGED</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>GAMMA-GLUTAMYLTRANSFERASE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="26" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>WEIGHT DECREASED</sub_title>
                <counts group_id="E1" subjects_affected="48" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>DECREASED APPETITE</sub_title>
                <counts group_id="E1" subjects_affected="59" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>HYPOKALAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>HYPOPHOSPHATAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>ARTHRALGIA</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>BACK PAIN</sub_title>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>MUSCULOSKELETAL CHEST PAIN</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>MUSCULOSKELETAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>MYALGIA</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>NECK PAIN</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>PAIN IN EXTREMITY</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>DIZZINESS</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>DYSGEUSIA</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>HEADACHE</sub_title>
                <counts group_id="E1" subjects_affected="31" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>PARAESTHESIA</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>ANXIETY</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>INSOMNIA</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>COUGH</sub_title>
                <counts group_id="E1" subjects_affected="33" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>DYSPNOEA</sub_title>
                <counts group_id="E1" subjects_affected="29" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>HAEMOPTYSIS</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>ALOPECIA</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>DRY SKIN</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>PRURITUS</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="140"/>
              </event>
              <event>
                <sub_title>RASH</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="140"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Novartis Pharmaceuticals</organization>
      <phone>862-778-8300</phone>
      <email>trialandresults.registries@novartis.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01685060
org study id: CLDK378A2201
secondary id: 2012-003432-24
nct id: NCT01685060
lead sponsor: 
has dmc: Yes
A single-arm, open-label, multicenter, phase II study. Treatment with LDK378 750 mg qd
      continued until the patient experienced unacceptable toxicity that precluded further
      treatment, discontinued treatment at the discretion of the investigator or patient, started a
      new anti-cancer therapy and/or died. LDK378 could be continued beyond RECIST-defined
      progressive disease (PD) as assessed by the investigator if, in the judgment of the
      investigator, there was evidence of clinical benefit. In these patients tumor assessment
      would continue as per the schedule of assessments until treatment with LDK378 was permanently
      discontinued. Patients who discontinued the study medication in the absence of progression
      continued to be followed for tumor assessment until the time of PD as assessed by the
      investigator
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Response Rate (ORR) to LDK378 Per Investigator Assessment
time frame: 6 cycles of 28 days up to 24 weeks
description: ORR per RECIST 1.1 calculated as the percentage of patients with a best overall confirmed response defined as complete response or partial response (CR+PR) as assessed by investigator. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
measure: ORR Per Blinded Independent Review Committee (BIRC) Assessment
time frame: 6 cycles of 28 days up to 24 weeks
description: ORR (CR+PR) by BIRC is calculated as the percentage of patients with a best overall confirmed response defined as complete response or partial response (CR+PR) as assessed by BIRC. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
measure: Duration of Response (DOR) by Investigator
time frame: 6 cycles of 28 days up to 24 weeks
description: DOR, calculated as the time from the date of the first confirmed CR or PR to the first documented progression or death due to any cause, by investigator. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
measure: Duration of Response (DOR) by BIRC
time frame: 6 cycles of 28 days up to 24 weeks
description: DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or death due to underlying cancer, by BIRC (Blinded Imaging Review Committee). CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
measure: Disease Control Rate (DCR)
time frame: 6 cycles of 28 days up to 24 weeks
description: DCR was calculated as the percentage of patients with best overall response of CR, PR, SD, or non-CR non-PD (NCRNPD), per RECIST 1.1 by investigator. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm 1. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. Non-CR/Non-PD (NCRNPD): refers to best overall responses that are neither CR nor PD per RECIST 1.1 criteria for patients with non-measurable disease only at baseline.
measure: Time to Response (TTR) Per Investigator
time frame: 6 cycles of 28 days up to 24 weeks
description: TTR is the time from date of start of treatment to the first CR or PR observed which were confirmed afterwards.
measure: Time to Response (TTR) Per BIRC
time frame: 6 cycles of 28 days up to 24 weeks
description: TTR is the time from date of start of treatment to the first CR or PR observed which are confirmed afterwards.
measure: Progression-free Survival (PFS) Per Investigator
time frame: 6 cycles of 28 days up to 24 weeks
description: PFS, defined as the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient had no event or when the patient received any further anticancer therapy in the absence of disease progression, progression-free survival was censored at the date of last adequate tumor assessment.
measure: Progression-free Survival (PFS) Per BIRC
time frame: 6 cycles of 28 days up to 24 weeks
description: PFS, defined as the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient had no event or when the patient received any further anticancer therapy in the absence of disease progression, progression-free survival was censored at the date of last adequate tumor assessment.
measure: Overall Intracranial Response Rate (OIRR) Per Investigator
time frame: 6 cycles of 28 days up to 24 weeks
description: OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who had measureable disease in the brain at baseline.
measure: Overall Intracranial Response Rate (OIRR) Per BIRC
time frame: 6 cycles of 28 days up to 24 weeks
description: OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who had measureable disease in the brain at baseline.
measure: Overall Survival (OS)
time frame: 6 cycles of 28 days up to 24 weeks
description: OS, defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient was not known to have died, survival was censored at the date of last known date patient alive.
arm group label: LDK378
arm group type: Experimental
description: Patients treated with ceritinib/LDK378 750 mg once-daily, fasted
intervention type: Drug
intervention name: LDK378
description: Ceritinib/LDK378 was supplied as 150 mg hard gelatin capsules and were administered orally, once-daily at a dose of 750 mg on a continuous dosing schedule (5 x 150 mg capsules).
arm group label: LDK378
other name: Ceritinib
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
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country: Canada
country: France
country: Germany
country: Hong Kong
country: Italy
country: Japan
country: Korea, Republic of
country: Netherlands
country: Singapore
country: Spain
country: United Kingdom
country: United States
country: Australia
country: Belgium
country: Sweden
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Ceritinib
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 