<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/NCT04427072</url>
  </required_header>
  <id_info>
    <org_study_id>CINC280A2301</org_study_id>
    <secondary_id>2020-001578-31</secondary_id>
    <nct_id>NCT04427072</nct_id>
  </id_info>
  <brief_title>Study of Capmatinib Efficacy in Comparison With Docetaxel in Previously Treated Participants With Non-small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutation</brief_title>
  <acronym>GeoMETry-III</acronym>
  <official_title>A Phase III, Randomized, Controlled, Open-label, Multicenter, Global Study of Capmatinib Versus SoC Docetaxel Chemotherapy in Previously Treated Patients With EGFR wt, ALK Negative, Locally Advanced or Metastatic (Stage IIIB/IIIC or IV) NSCLC Harboring MET Exon 14 Skipping Mutation (METΔex14).</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to learn whether the study drug (capmatinib) helps to control&#xD;
      lung cancer better compared to a single agent chemotherapy (docetaxel) and whether it is safe&#xD;
      when given to patients suffering from a particular type of lung cancer. This type of cancer&#xD;
      is called non-small cell lung cancer (NSCLC) with certain specific genetic alterations&#xD;
      (called mutations) of a gene called MET, within a specific part of the gene called exon 14.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Approximately 90 patients with advanced or metastatic lung cancer, with these specific&#xD;
      mutations in the MET gene but without changes in their epidermal growth factor receptor&#xD;
      (EGFR) or anaplastic lymphoma kinase (ALK) genes, will be enrolled in this study.&#xD;
      Participants will be randomly assigned to get either capmatinib or docetaxel in a 2 to 1&#xD;
      ratio. The randomization will be stratified by prior lines of systemic therapy received for&#xD;
      advanced/metastatic disease (one line vs. two lines).&#xD;
&#xD;
      During treatment, visits will be scheduled every 21 days.&#xD;
&#xD;
      For all participants, the respective treatment (either with capmatinib or docetaxel) may be&#xD;
      continued beyond initial disease progression as per RECIST 1.1 (as assessed by the&#xD;
      investigator and confirmed by BIRC) if, in the judgment of the investigator, there is&#xD;
      evidence of clinical benefit, and the participant wishes to continue on the study treatment.&#xD;
      After treatment discontinuation, all participants will be followed for safety evaluations&#xD;
      during the safety follow-up period, and the participant's status will be collected every 12&#xD;
      weeks as part of the survival follow-up.&#xD;
&#xD;
      Participants randomized to docetaxel treatment will be eligible to crossover to receive&#xD;
      capmatinib treatment after BIRC-confirmed, RECIST 1.1-defined progressive disease and after&#xD;
      meeting the eligibility criteria prior to crossover.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 25, 2020</start_date>
  <completion_date type="Anticipated">October 31, 2023</completion_date>
  <primary_completion_date type="Actual">February 15, 2023</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Participants randomized to docetaxel treatment will be eligible to crossover to receive capmatinib treatment after blinded independent review committee (BIRC)-confirmed, RECIST 1.1- defined disease progression.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression free survival (PFS) per blinded independent review committee (BIRC) using RECIST v1.1</measure>
    <time_frame>From randomization to the date of first documented progression or death from any cause, whichever comes first, assessed up to approximately 21 months</time_frame>
    <description>Progression free survival is defined as the time from the date of randomization to the date of the first documented progression assessed by BIRC according to RECIST 1.1, or death due to any cause</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response (ORR) per RECIST 1.1 by BIRC</measure>
    <time_frame>Up to approximately 21 months</time_frame>
    <description>Percentage of participants with confirmed best overall response (BOR) of complete response (CR) or partial response (PR), assessed by BIRC according to RECIST 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response (ORR) per RECIST 1.1 by investigator</measure>
    <time_frame>Up to approximately 21 months</time_frame>
    <description>Percentage of participants with confirmed BOR of CR or PR, assessed by local review according to RECIST 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to response (TTR) per RECIST 1.1 by BIRC</measure>
    <time_frame>From date of randomization to first documented response of either CR or PR, assessed up to approximately 21 months</time_frame>
    <description>Time from date of randomization to first documented response of either CR or PR, which must be subsequently confirmed, assessed by BIRC according to RECIST 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to response (TTR) per RECIST 1.1 by investigator</measure>
    <time_frame>From date of randomization to first documented response of either CR or PR, assessed up to approximately 21 months</time_frame>
    <description>Time from date of randomization to first documented response of either CR or PR, which must be subsequently confirmed, assessed by local review according to RECIST 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR) per RECIST 1.1 by BIRC</measure>
    <time_frame>From first documented response to first documented progression or death due to any cause, whichever comes first, assessed up to approximately 21 months</time_frame>
    <description>Time from the date of first documented response (CR or PR) to the first documented progression by BIRC per RECIST 1.1 or death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR) per RECIST 1.1 by investigator</measure>
    <time_frame>From first documented response to first documented progression or death due to any cause, whichever comes first, assessed up to approximately 21 months</time_frame>
    <description>Time from the date of first documented response (CR or PR) to the first documented progression by local review per RECIST 1.1 or death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR) per RECIST 1.1 by BIRC</measure>
    <time_frame>Up to approximately 21 months</time_frame>
    <description>Percentage of participants with a BOR of confirmed CR, PR and stable disease (SD) assessed by BIRC according to RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR) per RECIST 1.1 by investigator</measure>
    <time_frame>Up to approximately 21 months</time_frame>
    <description>Percentage of participants with a BOR of confirmed CR, PR and SD assessed by local review according to RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS) per investigator using RECIST v1.1</measure>
    <time_frame>From randomization to the date of first documented progression or death from any cause, whichever comes first, assessed up to approximately 21 months</time_frame>
    <description>Time from the date of randomization to the date of the first documented progression assessed by local review according to RECIST 1.1, or death due to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>From randomization to death due to any cause, assessed up to approximately 42 months</time_frame>
    <description>OS is defined as the time from the date of randomization to the date of death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall intracranial response rate (OIRR)</measure>
    <time_frame>Up to approximately 21 months</time_frame>
    <description>Percentage of participants with confirmed best overall intracranial response (BOIR) of CR or partial response (PR), as assessed by BIRC review per RANO-BM criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of intracranial response (DOIR)</measure>
    <time_frame>From date of first documented intracranial response (CR or PR) to first documented intracranial progression, assessed up to approximately 21 months</time_frame>
    <description>Time from date of first documented intracranial response (CR or PR) to first documented intracranial progression per RANO-BM assessed by BIRC or date of death due to underlying cause of cancer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to intracranial response (TTIR)</measure>
    <time_frame>From date of randomization to first documented intracranial response of either CR or PR, assessed up to approximately 21 months</time_frame>
    <description>Time from date of randomization to first documented intracranial response of either CR or PR, per RANO-BM criteria and assessed by BIRC, which must be subsequently confirmed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intracranial disease control rate (IDCR)</measure>
    <time_frame>Up to approximately 21 months</time_frame>
    <description>Percentage of participants with a BOR of confirmed CR, PR and stable disease (SD) (or non-CR/non-PD) per RANO-BM, assessed by BIRC.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma capmatinib concentration</measure>
    <time_frame>Cycle (C) 1 Day (D) 15 pre-dose, 1 and 4 hours post-dose, C3 D1 pre-dose. Each cycle duration is 21 days.</time_frame>
    <description>Plasma concentrations of capmatinib. Blood samples will be collected at indicated time points for pharmacokinetic analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in score as per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30</measure>
    <time_frame>Cycle (C) 1 Day (D) 1, C3 D1 and then every 6 weeks up to approximately 21 months, end of treatment and 6, 12 , 18 weeks post treatment . Each cycle duration is 21 days.</time_frame>
    <description>EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. The questionnaire is composed of both multi-item scales and single-item measures based on the participants experience over the past week. These include five domains (physical, role, emotional, cognitive and social functioning), three symptom scales (fatigue, nausea/vomiting, and pain), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/HRQoL scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.&#xD;
Change from baseline in EORTC QLQ-C30 scores will be assessed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in score as per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Lung Cancer Module (QLQ-LC13)</measure>
    <time_frame>Cycle (C) 1 Day (D) 1, C3 D1 and then every 6 weeks up to approximately 21 months, end of treatment and 6, 12 , 18 weeks post treatment . Each cycle duration is 21 days.</time_frame>
    <description>EORTC QLQ-LC13 is a 13-item lung cancer specific questionnaire. The five domains of the questionnaire include pain, dyspnea, coughing and hemoptysis, and are based on their presence over the past week. All but the pain domain are scored on a 4 point Likert scale ranging from &quot;not at all&quot; to &quot;very much&quot;. Pain is score based on its presence, hence yes or no. A higher score indicates a higher presence of symptoms.&#xD;
Change from baseline in EORTC QLQ-LC13 scores will be assessed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in score as per European Quality of Life 5-Dimension 5-Level (EQ-5D-5L) questionnaire</measure>
    <time_frame>Cycle (C) 1 Day (D) 1, C3 D1 and then every 6 weeks up to approximately 21 months, end of treatment and 6, 12 , 18 weeks post treatment . Each cycle duration is 21 days.</time_frame>
    <description>EQ-5D-5L is a standardized measure to assess the overall health-related quality of life in patients. The EQ-5D-5L consists of 2 parts- the descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with 5 levels: from 1 (no problems) to 5 (extreme problems). The EQ VAS is a self-perceived health score assessed using a visual analogue scale that ranges from 0 (the worst imaginable health) to 100 (the best imaginable health), with higher scores indicating higher health utility.&#xD;
Change from baseline in EQ-5D-5L scores will be assessed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to symptom deterioration for chest pain, cough and dyspnea assessed using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Lung Cancer Module (QLQ-LC13)</measure>
    <time_frame>Cycle (C) 1 Day (D) 1, C3 D1 and then every 6 weeks up to approximately 21 months, end of treatment and 6, 12 , 18 weeks post treatment. Each cycle duration is 21 days.</time_frame>
    <description>EORTC QLQ-LC13 is a 13-item lung cancer specific questionnaire. The five domains of the questionnaire include pain, dyspnea, coughing and hemoptysis, and are based on their presence over the past week. All but the pain domain are scored on a 4 point Likert scale ranging from &quot;not at all&quot; to &quot;very much&quot;. Pain is score based on its presence, hence yes or no. A higher score indicates a higher presence of symptoms.&#xD;
Time to symptom deterioration for chest pain, cough and dyspnea will be assessed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to deterioration for global health status /QoL assessed using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30</measure>
    <time_frame>Cycle (C) 1 Day (D) 1, C3 D1 and then every 6 weeks up to approximately 21 months, end of treatment and 6, 12 , 18 weeks post treatment. Each cycle duration is 21 days.</time_frame>
    <description>EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. The questionnaire is composed of both multi-item scales and single-item measures based on the participants experience over the past week. These include five domains (physical, role, emotional, cognitive and social functioning), three symptom scales (fatigue, nausea/vomiting, and pain), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/HRQoL scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.&#xD;
Time to deterioration in QoL from EORTC-QLQ-C30 will be assessed.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">22</enrollment>
  <condition>Carcinoma, Non-Small-Cell Lung</condition>
  <arm_group>
    <arm_group_label>Capmatinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>400mg of capmatinib tablets, administered orally twice daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Docetaxel</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Docetaxel 75 mg/m2 solution administered by intravenous infusion on Day 1 of every 21-day cycle</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capmatinib</intervention_name>
    <description>400mg of capmatinib tablets administered orally twice daily</description>
    <arm_group_label>Capmatinib</arm_group_label>
    <other_name>INC280</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Docetaxel</intervention_name>
    <description>Docetaxel 75 mg/m2 by intravenous infusion every 21 days</description>
    <arm_group_label>Docetaxel</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Stage IIIB/IIIC (not amenable to surgery, radiation or multi modality therapy) or IV&#xD;
             NSCLC (according to Version 8 of the American Joint Committee on Cancer (AJCC) Staging&#xD;
             Manual) at the time of study entry.&#xD;
&#xD;
          -  Histologically or cytologically confirmed diagnosis of NSCLC that is:&#xD;
&#xD;
               1. EGFR wt. Assessed as part of participant's standard of care by a validated test&#xD;
                  for EGFR mutations as per local guidelines. The EGFR wt status (for EGFR&#xD;
                  mutations that predict sensitivity to EGFR therapy, including, but not limited to&#xD;
                  exon 19 deletions and exon 21 L858R substitution mutations.&#xD;
&#xD;
               2. AND ALK rearrangement negative. Assessed as part of participant's standard of&#xD;
                  care by a validated test.&#xD;
&#xD;
               3. AND has METΔex14 mutation as determined by Novartis-designated central laboratory&#xD;
                  or by locally performed, tissue-based test, validated according to local&#xD;
                  regulation, from a Clinical Laboratory Improvement Amendments (CLIA)-certified US&#xD;
                  laboratory or an accredited local laboratory outside of the US. The positive&#xD;
                  METΔex14 mutation result as determined per local test must be documented in the&#xD;
                  participant's source documents and in the CRF prior to entering main screening.&#xD;
&#xD;
          -  Mandatory provision of a formalin-fixed, paraffin embedded tumor tissue sample&#xD;
             (archival tumor block or slides, or a newly obtained tumor sample) with quality and&#xD;
             quantity sufficient to allow assessment of METΔex14 mutation status (as defined in the&#xD;
             study [laboratory manual]). This pertains to all participants, including those who&#xD;
             have a METΔex14 mutation result from a local test. Tumor samples must contain at least&#xD;
             10% tumor content.&#xD;
&#xD;
             6. Participants must have progressed on one or two prior lines of&#xD;
&#xD;
          -  Progressed on one or two prior lines of systemic therapy for advanced/metastatic&#xD;
             disease (stage IIIB/IIIC [not candidates for surgery, radiation or multi modality&#xD;
             therapy] or IV NSCLC) and must be docetaxel naïve and candidates for single agent&#xD;
             chemotherapy (docetaxel). Treatment failure is defined as documented disease&#xD;
             progression or intolerance to treatment., however participants must have progressed on&#xD;
             or after the last therapy before study entry.&#xD;
&#xD;
          -  At least one measurable lesion as defined by RECIST 1.1&#xD;
&#xD;
          -  Adequate organ function&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.&#xD;
&#xD;
          -  Participants must have a life expectancy of at least 3 months.&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Prior treatment with any MET inhibitor or HGF-targeting therapy.&#xD;
&#xD;
          -  Participants 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;
          -  Participants with known druggable molecular alterations (such as ROS1and RET&#xD;
             rearrangement, BRAF mutation, KRAS mutation, NTRK fusion, etc.) which might be a&#xD;
             candidate for alternative targeted therapies.&#xD;
&#xD;
          -  Presence or history of interstitial lung disease or interstitial pneumonitis,&#xD;
             including clinically significant radiation pneumonitis (i.e., affecting activities of&#xD;
             daily living or requiring therapeutic intervention).&#xD;
&#xD;
          -  Substance abuse, active infection or other severe, acute, or chronic medical or&#xD;
             psychotic conditions or laboratory abnormalities that in the opinion of the&#xD;
             investigator may increase the risk associated with study participation&#xD;
&#xD;
        Other protocol-defined inclusion/exclusion criteria may apply.&#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>Novartis Investigative Site</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sao Paulo</city>
        <state>SP</state>
        <zip>04014-002</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Paris</city>
        <zip>75231</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Pierre Benite</city>
        <zip>69495</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Gauting</city>
        <state>Bayern</state>
        <zip>82131</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Koeln</city>
        <zip>50937</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>New Delhi</city>
        <state>Delhi</state>
        <zip>110076</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Milano</city>
        <state>MI</state>
        <zip>20162</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Roma</city>
        <state>RM</state>
        <zip>00128</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Seoul</city>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Nijmegen</city>
        <zip>6500 HB</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Matosinhos</city>
        <zip>4454 513</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Valencia</city>
        <state>Comunidad Valenciana</state>
        <zip>46026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Madrid</city>
        <zip>28009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Brazil</country>
    <country>France</country>
    <country>Germany</country>
    <country>India</country>
    <country>Italy</country>
    <country>Korea, Republic of</country>
    <country>Netherlands</country>
    <country>Portugal</country>
    <country>Spain</country>
  </location_countries>
  <removed_countries>
    <country>Australia</country>
    <country>Bulgaria</country>
    <country>Hungary</country>
    <country>Lithuania</country>
    <country>Malaysia</country>
    <country>Russian Federation</country>
    <country>South Africa</country>
    <country>Thailand</country>
    <country>Vietnam</country>
  </removed_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>June 9, 2020</study_first_submitted>
  <study_first_submitted_qc>June 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>July 24, 2023</last_update_submitted>
  <last_update_submitted_qc>July 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Non small cell lung cancer</keyword>
  <keyword>Non small cell lung carcinoma</keyword>
  <keyword>NSCLC</keyword>
  <keyword>INC280</keyword>
  <keyword>capmatinib</keyword>
  <keyword>MET mutation</keyword>
  <keyword>MET exon14</keyword>
  <keyword>MET exon14 skipping</keyword>
  <keyword>MET exon14 deletion</keyword>
  <keyword>METex14</keyword>
  <keyword>METex14del</keyword>
  <keyword>MET∆ex14</keyword>
  <keyword>EGFRwt</keyword>
  <keyword>Epidermal growth factor receptor wild type</keyword>
  <keyword>ALK negative</keyword>
  <keyword>docetaxel</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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>Docetaxel</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.&#xD;
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04427072
org study id: CINC280A2301
secondary id: 2020-001578-31
nct id: NCT04427072
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of the study is to learn whether the study drug (capmatinib) helps to control
      lung cancer better compared to a single agent chemotherapy (docetaxel) and whether it is safe
      when given to patients suffering from a particular type of lung cancer. This type of cancer
      is called non-small cell lung cancer (NSCLC) with certain specific genetic alterations
      (called mutations) of a gene called MET, within a specific part of the gene called exon 14.
Approximately 90 patients with advanced or metastatic lung cancer, with these specific
      mutations in the MET gene but without changes in their epidermal growth factor receptor
      (EGFR) or anaplastic lymphoma kinase (ALK) genes, will be enrolled in this study.
      Participants will be randomly assigned to get either capmatinib or docetaxel in a 2 to 1
      ratio. The randomization will be stratified by prior lines of systemic therapy received for
      advanced/metastatic disease (one line vs. two lines).

      During treatment, visits will be scheduled every 21 days.

      For all participants, the respective treatment (either with capmatinib or docetaxel) may be
      continued beyond initial disease progression as per RECIST 1.1 (as assessed by the
      investigator and confirmed by BIRC) if, in the judgment of the investigator, there is
      evidence of clinical benefit, and the participant wishes to continue on the study treatment.
      After treatment discontinuation, all participants will be followed for safety evaluations
      during the safety follow-up period, and the participant's status will be collected every 12
      weeks as part of the survival follow-up.

      Participants randomized to docetaxel treatment will be eligible to crossover to receive
      capmatinib treatment after BIRC-confirmed, RECIST 1.1-defined progressive disease and after
      meeting the eligibility criteria prior to crossover.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participants randomized to docetaxel treatment will be eligible to crossover to receive capmatinib treatment after blinded independent review committee (BIRC)-confirmed, RECIST 1.1- defined disease progression.
primary purpose: Treatment
masking: None (Open Label)
measure: Progression free survival (PFS) per blinded independent review committee (BIRC) using RECIST v1.1
time frame: From randomization to the date of first documented progression or death from any cause, whichever comes first, assessed up to approximately 21 months
description: Progression free survival is defined as the time from the date of randomization to the date of the first documented progression assessed by BIRC according to RECIST 1.1, or death due to any cause
measure: Overall response (ORR) per RECIST 1.1 by BIRC
time frame: Up to approximately 21 months
description: Percentage of participants with confirmed best overall response (BOR) of complete response (CR) or partial response (PR), assessed by BIRC according to RECIST 1.1.
measure: Overall response (ORR) per RECIST 1.1 by investigator
time frame: Up to approximately 21 months
description: Percentage of participants with confirmed BOR of CR or PR, assessed by local review according to RECIST 1.1.
measure: Time to response (TTR) per RECIST 1.1 by BIRC
time frame: From date of randomization to first documented response of either CR or PR, assessed up to approximately 21 months
description: Time from date of randomization to first documented response of either CR or PR, which must be subsequently confirmed, assessed by BIRC according to RECIST 1.1.
measure: Time to response (TTR) per RECIST 1.1 by investigator
time frame: From date of randomization to first documented response of either CR or PR, assessed up to approximately 21 months
description: Time from date of randomization to first documented response of either CR or PR, which must be subsequently confirmed, assessed by local review according to RECIST 1.1.
measure: Duration of response (DOR) per RECIST 1.1 by BIRC
time frame: From first documented response to first documented progression or death due to any cause, whichever comes first, assessed up to approximately 21 months
description: Time from the date of first documented response (CR or PR) to the first documented progression by BIRC per RECIST 1.1 or death due to any cause.
measure: Duration of response (DOR) per RECIST 1.1 by investigator
time frame: From first documented response to first documented progression or death due to any cause, whichever comes first, assessed up to approximately 21 months
description: Time from the date of first documented response (CR or PR) to the first documented progression by local review per RECIST 1.1 or death due to any cause.
measure: Disease Control Rate (DCR) per RECIST 1.1 by BIRC
time frame: Up to approximately 21 months
description: Percentage of participants with a BOR of confirmed CR, PR and stable disease (SD) assessed by BIRC according to RECIST 1.1
measure: Disease Control Rate (DCR) per RECIST 1.1 by investigator
time frame: Up to approximately 21 months
description: Percentage of participants with a BOR of confirmed CR, PR and SD assessed by local review according to RECIST 1.1
measure: Progression free survival (PFS) per investigator using RECIST v1.1
time frame: From randomization to the date of first documented progression or death from any cause, whichever comes first, assessed up to approximately 21 months
description: Time from the date of randomization to the date of the first documented progression assessed by local review according to RECIST 1.1, or death due to any cause
measure: Overall survival (OS)
time frame: From randomization to death due to any cause, assessed up to approximately 42 months
description: OS is defined as the time from the date of randomization to the date of death due to any cause.
measure: Overall intracranial response rate (OIRR)
time frame: Up to approximately 21 months
description: Percentage of participants with confirmed best overall intracranial response (BOIR) of CR or partial response (PR), as assessed by BIRC review per RANO-BM criteria.
measure: Duration of intracranial response (DOIR)
time frame: From date of first documented intracranial response (CR or PR) to first documented intracranial progression, assessed up to approximately 21 months
description: Time from date of first documented intracranial response (CR or PR) to first documented intracranial progression per RANO-BM assessed by BIRC or date of death due to underlying cause of cancer.
measure: Time to intracranial response (TTIR)
time frame: From date of randomization to first documented intracranial response of either CR or PR, assessed up to approximately 21 months
description: Time from date of randomization to first documented intracranial response of either CR or PR, per RANO-BM criteria and assessed by BIRC, which must be subsequently confirmed.
measure: Intracranial disease control rate (IDCR)
time frame: Up to approximately 21 months
description: Percentage of participants with a BOR of confirmed CR, PR and stable disease (SD) (or non-CR/non-PD) per RANO-BM, assessed by BIRC.
measure: Plasma capmatinib concentration
time frame: Cycle (C) 1 Day (D) 15 pre-dose, 1 and 4 hours post-dose, C3 D1 pre-dose. Each cycle duration is 21 days.
description: Plasma concentrations of capmatinib. Blood samples will be collected at indicated time points for pharmacokinetic analysis.
measure: Change from baseline in score as per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30
time frame: Cycle (C) 1 Day (D) 1, C3 D1 and then every 6 weeks up to approximately 21 months, end of treatment and 6, 12 , 18 weeks post treatment . Each cycle duration is 21 days.
description: EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. The questionnaire is composed of both multi-item scales and single-item measures based on the participants experience over the past week. These include five domains (physical, role, emotional, cognitive and social functioning), three symptom scales (fatigue, nausea/vomiting, and pain), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/HRQoL scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
Change from baseline in EORTC QLQ-C30 scores will be assessed
measure: Change from baseline in score as per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Lung Cancer Module (QLQ-LC13)
time frame: Cycle (C) 1 Day (D) 1, C3 D1 and then every 6 weeks up to approximately 21 months, end of treatment and 6, 12 , 18 weeks post treatment . Each cycle duration is 21 days.
description: EORTC QLQ-LC13 is a 13-item lung cancer specific questionnaire. The five domains of the questionnaire include pain, dyspnea, coughing and hemoptysis, and are based on their presence over the past week. All but the pain domain are scored on a 4 point Likert scale ranging from "not at all" to "very much". Pain is score based on its presence, hence yes or no. A higher score indicates a higher presence of symptoms.
Change from baseline in EORTC QLQ-LC13 scores will be assessed
measure: Change from baseline in score as per European Quality of Life 5-Dimension 5-Level (EQ-5D-5L) questionnaire
time frame: Cycle (C) 1 Day (D) 1, C3 D1 and then every 6 weeks up to approximately 21 months, end of treatment and 6, 12 , 18 weeks post treatment . Each cycle duration is 21 days.
description: EQ-5D-5L is a standardized measure to assess the overall health-related quality of life in patients. The EQ-5D-5L consists of 2 parts- the descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with 5 levels: from 1 (no problems) to 5 (extreme problems). The EQ VAS is a self-perceived health score assessed using a visual analogue scale that ranges from 0 (the worst imaginable health) to 100 (the best imaginable health), with higher scores indicating higher health utility.
Change from baseline in EQ-5D-5L scores will be assessed
measure: Time to symptom deterioration for chest pain, cough and dyspnea assessed using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Lung Cancer Module (QLQ-LC13)
time frame: Cycle (C) 1 Day (D) 1, C3 D1 and then every 6 weeks up to approximately 21 months, end of treatment and 6, 12 , 18 weeks post treatment. Each cycle duration is 21 days.
description: EORTC QLQ-LC13 is a 13-item lung cancer specific questionnaire. The five domains of the questionnaire include pain, dyspnea, coughing and hemoptysis, and are based on their presence over the past week. All but the pain domain are scored on a 4 point Likert scale ranging from "not at all" to "very much". Pain is score based on its presence, hence yes or no. A higher score indicates a higher presence of symptoms.
Time to symptom deterioration for chest pain, cough and dyspnea will be assessed
measure: Time to deterioration for global health status /QoL assessed using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30
time frame: Cycle (C) 1 Day (D) 1, C3 D1 and then every 6 weeks up to approximately 21 months, end of treatment and 6, 12 , 18 weeks post treatment. Each cycle duration is 21 days.
description: EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. The questionnaire is composed of both multi-item scales and single-item measures based on the participants experience over the past week. These include five domains (physical, role, emotional, cognitive and social functioning), three symptom scales (fatigue, nausea/vomiting, and pain), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/HRQoL scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
Time to deterioration in QoL from EORTC-QLQ-C30 will be assessed.
arm group label: Capmatinib
arm group type: Experimental
description: 400mg of capmatinib tablets, administered orally twice daily
arm group label: Docetaxel
arm group type: Active Comparator
description: Docetaxel 75 mg/m2 solution administered by intravenous infusion on Day 1 of every 21-day cycle
intervention type: Drug
intervention name: Capmatinib
description: 400mg of capmatinib tablets administered orally twice daily
arm group label: Capmatinib
other name: INC280
intervention type: Drug
intervention name: Docetaxel
description: Docetaxel 75 mg/m2 by intravenous infusion every 21 days
arm group label: Docetaxel
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: Belgium
country: Brazil
country: France
country: Germany
country: India
country: Italy
country: Korea, Republic of
country: Netherlands
country: Portugal
country: Spain
country: Australia
country: Bulgaria
country: Hungary
country: Lithuania
country: Malaysia
country: Russian Federation
country: South Africa
country: Thailand
country: Vietnam
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Docetaxel
sharing ipd: Yes
ipd description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com