<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/NCT03040973</url>
  </required_header>
  <id_info>
    <org_study_id>CINC280A2X02B</org_study_id>
    <secondary_id>2016-005144-42</secondary_id>
    <nct_id>NCT03040973</nct_id>
  </id_info>
  <brief_title>Study to Allow Patients Previously Participating in a Novartis Sponsored Trial to Continue Receiving Capmatinib Treatment as Single Agent or in Combination With Other Treatments or the Combination Treatment Alone</brief_title>
  <official_title>An Open-label, Multi-center, Global, Rollover Study for Patients Who Have Previously Been Treated With Capmatinib (INC280) as Monotherapy or in Combination in a Novartis Sponsored Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess long-term safety and provide continued study treatment&#xD;
      access to eligible participants who are judged by the Investigator to benefit from continued&#xD;
      treatment with capmatinib monotherapy or in combination with other treatments or with the&#xD;
      combination treatment alone in a Novartis sponsored study&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, multi-center, rollover study to assess long-term safety in&#xD;
      participants who have completed a prior Novartis-sponsored study, that have fulfilled the&#xD;
      eligibility requirements and are judged by the Investigator to benefit from continued&#xD;
      treatment with capmatinib given as monotherapy or in combination with other treatments or&#xD;
      with the combination treatment alone.&#xD;
&#xD;
      There will be no screening period for this study. After providing informed consent, all&#xD;
      eligible participants will begin their treatment within the rollover study. Participants&#xD;
      should return to the study center for resupply of the study medication/s and for safety&#xD;
      assessment following the usual local practice. During a public health emergency as declared&#xD;
      by local or regional authorities (i.e. pandemic, epidemic or natural disaster) that limits or&#xD;
      prevents on-site study visits, alternative methods of providing continuing care may be&#xD;
      implemented by the Investigator as the situation dictates.&#xD;
&#xD;
      Participants will continue to be treated until they are no longer benefitting from the study&#xD;
      treatment in the opinion of the treating physician, develop unacceptable toxicities that&#xD;
      preclude further treatment with the study treatment, disease progression, withdrawal of&#xD;
      consent, discontinuation at the discretion of the Investigator, initiation of new anticancer&#xD;
      therapy, until the study treatment is commercially available and reimbursed or/and available&#xD;
      under any other local mechanism (such as compassionate use, named patient program) for the&#xD;
      appropriate indication and/or discontinuation for any other reason. Participants receiving&#xD;
      capmatinib as part of a combination therapy could continue treatment only with capmatinib or&#xD;
      with the combination treatment as single agent in case one of the two compounds is&#xD;
      permanently discontinued, if in the opinion of the treating physician they are still&#xD;
      benefitting from the treatment.&#xD;
&#xD;
      A patient will reach the end of rollover study when study treatment is permanently&#xD;
      discontinued and the end of treatment visit has been performed. All participants will be&#xD;
      followed up for safety for 30 days after the last dose of study treatment or until SAE is&#xD;
      resolved as required, whichever is later.&#xD;
&#xD;
      The study is expected to remain open for up to 10 years or until such time that all enrolled&#xD;
      participants no longer need treatment with study treatment(s) or Novartis decides to stop the&#xD;
      development program, whichever comes first.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 4, 2017</start_date>
  <completion_date type="Anticipated">July 30, 2027</completion_date>
  <primary_completion_date type="Anticipated">July 30, 2027</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants with Adverse Events as a Measure of Safety and Tolerability</measure>
    <time_frame>Day 1 up to 10 years, assessed every 12 weeks</time_frame>
    <description>Collection of adverse events and serious adverse events at every visit. Safety assessment will be performed and include local laboratory test monitoring in addition to local standard of care assessments.</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Advanced Solid Tumors Which Are cMET-dependent</condition>
  <arm_group>
    <arm_group_label>Capmatinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Starting dose of study treatment for patients in this protocol should be the same as the dose provided in the parent protocol at the time when the rollover protocol is initiated. Dose modifications are permitted.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Capmatinib + Nazartinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Starting dose of the study treatment for patients should be the same as the dose provided in the parent protocol at the time when the rollover protocol is initiated. Dose modifications are permitted.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Capmatinib + Gefitinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Starting dose of the study treatment for patients in this protocol should be the same as the dose provided in the parent protocol at the time when the rollover protocol is initiated. Dose modifications are permitted.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Capmatinib + Osimertinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Starting dose of the study treatment for patients in this protocol should be the same as the dose provided in the parent protocol at the time when the rollover protocol is initiated. Dose modifications are permitted.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capmatinib</intervention_name>
    <description>Tablet for oral use; 150 mg, 200 mg; twice a day</description>
    <arm_group_label>Capmatinib</arm_group_label>
    <arm_group_label>Capmatinib + Gefitinib</arm_group_label>
    <arm_group_label>Capmatinib + Nazartinib</arm_group_label>
    <arm_group_label>Capmatinib + Osimertinib</arm_group_label>
    <other_name>INC280</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nazartinib</intervention_name>
    <description>Capsule for oral use; 25 mg, 50 mg; once a day</description>
    <arm_group_label>Capmatinib + Nazartinib</arm_group_label>
    <other_name>EGF816</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gefitinib</intervention_name>
    <description>tablets for oral use; 250mg; once a day</description>
    <arm_group_label>Capmatinib + Gefitinib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Osimertinib</intervention_name>
    <description>Tablets for oral use; 40 mg, 80 mg; once a day.</description>
    <arm_group_label>Capmatinib + Osimertinib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. Participant is currently receiving capmatinib treatment (within Novartis-sponsored&#xD;
             study which is eligible and approved to transition participants to rollover study) as&#xD;
             single agent or in combination or is receiving a combination treatment alone. This&#xD;
             includes all participants treated with capmatinib in combination with other treatment&#xD;
             that permanently discontinued capmatinib for any reason but are still receiving the&#xD;
             combination treatment as single agent. In order to receive the combination treatment&#xD;
             as single agent in the rollover study, the treatment needs to be not accessible to the&#xD;
             participant outside a clinical trial (e.g. commercially not available or reimbursed).&#xD;
&#xD;
          2. Participant is currently deriving clinical benefit from study treatment as determined&#xD;
             by the Investigator&#xD;
&#xD;
          3. Willingness and ability to comply with scheduled visits, treatment plans and any other&#xD;
             study procedures&#xD;
&#xD;
          4. Written informed consent obtained prior to enrolling in the rollover study and&#xD;
             receiving study medication. If consent cannot be expressed in writing, it must be&#xD;
             formally documented and witnessed, ideally via an independent trusted witness.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Participant is currently not receiving any study treatment due to unresolved&#xD;
             toxicities for which study treatment dosing has been interrupted or permanently&#xD;
             discontinued in the parent protocol (participants meeting all other eligibility&#xD;
             criteria may be enrolled once toxicities have resolved to allow study treatment dosing&#xD;
             to resume)&#xD;
&#xD;
          2. Pregnant or nursing (lactating) women&#xD;
&#xD;
          3. Women of child-bearing potential, defined as all women physiologically capable of&#xD;
             becoming pregnant, unless they are using highly effective methods of contraception&#xD;
             while taking study treatment and for at least 7 days or following combination&#xD;
             treatment parent trial recommendation (whichever is longer) of study treatment after&#xD;
             stopping medication. Highly effective contraception methods include:&#xD;
&#xD;
          4. Concurrent participation in another clinical study other than a parent clinical study&#xD;
&#xD;
          5. Participants who received live vaccines (e.g., intranasal influenza, measles, mumps,&#xD;
             rubella, oral polio, BCG, yellow fever, varicella, TY21a typhoid vaccines and COVID-19&#xD;
             vaccines) within 30 days prior to the first dose of study treatment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Toni Wozniak, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Barbara Ann Karmanos Cancer Institute</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Novartis Pharmaceuticals</last_name>
    <phone>1-888-669-6682</phone>
    <email>Novartis.email@novartis.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Novartis Pharmaceuticals</last_name>
    <phone>+41613241111</phone>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Massachusetts General Hospital MGH Cancer Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Aminta Kendall Scott</last_name>
      <email>AZSCOTT@mgh.harvard.edu</email>
    </contact>
    <investigator>
      <last_name>Rebecca Heist</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 1Z2</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Copenhagen</city>
        <zip>DK-2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Dijon</city>
        <state>Cote D Or</state>
        <zip>21034</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Dresden</city>
        <zip>01307</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hannover</city>
        <zip>30625</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Koeln</city>
        <zip>50937</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Milano</city>
        <state>MI</state>
        <zip>20141</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Perugia</city>
        <state>PG</state>
        <zip>06129</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Seoul</city>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Seoul</city>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Seoul</city>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Singapore</city>
        <zip>119074</zip>
        <country>Singapore</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Canada</country>
    <country>Denmark</country>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Korea, Republic of</country>
    <country>Singapore</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>January 31, 2017</study_first_submitted>
  <study_first_submitted_qc>January 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 2, 2017</study_first_posted>
  <last_update_submitted>May 4, 2023</last_update_submitted>
  <last_update_submitted_qc>May 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>capmatinib</keyword>
  <keyword>INC280</keyword>
  <keyword>Nazartinib</keyword>
  <keyword>Gefitinib</keyword>
  <keyword>Osimertinib</keyword>
  <keyword>EGF816</keyword>
  <keyword>NSCLC</keyword>
  <keyword>EGFR inhibitor</keyword>
  <keyword>METex14</keyword>
  <keyword>Non Small Cell Lung Cancer</keyword>
  <keyword>MET inhibitors</keyword>
  <keyword>rollover protocol</keyword>
  <keyword>parent protocol</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gefitinib</mesh_term>
    <mesh_term>Osimertinib</mesh_term>
    <mesh_term>Nazartinib</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/NCT03040973
org study id: CINC280A2X02B
secondary id: 2016-005144-42
nct id: NCT03040973
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to assess long-term safety and provide continued study treatment
      access to eligible participants who are judged by the Investigator to benefit from continued
      treatment with capmatinib monotherapy or in combination with other treatments or with the
      combination treatment alone in a Novartis sponsored study
This is an open-label, multi-center, rollover study to assess long-term safety in
      participants who have completed a prior Novartis-sponsored study, that have fulfilled the
      eligibility requirements and are judged by the Investigator to benefit from continued
      treatment with capmatinib given as monotherapy or in combination with other treatments or
      with the combination treatment alone.

      There will be no screening period for this study. After providing informed consent, all
      eligible participants will begin their treatment within the rollover study. Participants
      should return to the study center for resupply of the study medication/s and for safety
      assessment following the usual local practice. During a public health emergency as declared
      by local or regional authorities (i.e. pandemic, epidemic or natural disaster) that limits or
      prevents on-site study visits, alternative methods of providing continuing care may be
      implemented by the Investigator as the situation dictates.

      Participants will continue to be treated until they are no longer benefitting from the study
      treatment in the opinion of the treating physician, develop unacceptable toxicities that
      preclude further treatment with the study treatment, disease progression, withdrawal of
      consent, discontinuation at the discretion of the Investigator, initiation of new anticancer
      therapy, until the study treatment is commercially available and reimbursed or/and available
      under any other local mechanism (such as compassionate use, named patient program) for the
      appropriate indication and/or discontinuation for any other reason. Participants receiving
      capmatinib as part of a combination therapy could continue treatment only with capmatinib or
      with the combination treatment as single agent in case one of the two compounds is
      permanently discontinued, if in the opinion of the treating physician they are still
      benefitting from the treatment.

      A patient will reach the end of rollover study when study treatment is permanently
      discontinued and the end of treatment visit has been performed. All participants will be
      followed up for safety for 30 days after the last dose of study treatment or until SAE is
      resolved as required, whichever is later.

      The study is expected to remain open for up to 10 years or until such time that all enrolled
      participants no longer need treatment with study treatment(s) or Novartis decides to stop the
      development program, whichever comes first.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
time frame: Day 1 up to 10 years, assessed every 12 weeks
description: Collection of adverse events and serious adverse events at every visit. Safety assessment will be performed and include local laboratory test monitoring in addition to local standard of care assessments.
arm group label: Capmatinib
arm group type: Experimental
description: Starting dose of study treatment for patients in this protocol should be the same as the dose provided in the parent protocol at the time when the rollover protocol is initiated. Dose modifications are permitted.
arm group label: Capmatinib + Nazartinib
arm group type: Experimental
description: Starting dose of the study treatment for patients should be the same as the dose provided in the parent protocol at the time when the rollover protocol is initiated. Dose modifications are permitted.
arm group label: Capmatinib + Gefitinib
arm group type: Experimental
description: Starting dose of the study treatment for patients in this protocol should be the same as the dose provided in the parent protocol at the time when the rollover protocol is initiated. Dose modifications are permitted.
arm group label: Capmatinib + Osimertinib
arm group type: Experimental
description: Starting dose of the study treatment for patients in this protocol should be the same as the dose provided in the parent protocol at the time when the rollover protocol is initiated. Dose modifications are permitted.
intervention type: Drug
intervention name: Capmatinib
description: Tablet for oral use; 150 mg, 200 mg; twice a day
arm group label: Capmatinib
arm group label: Capmatinib + Gefitinib
arm group label: Capmatinib + Nazartinib
arm group label: Capmatinib + Osimertinib
other name: INC280
intervention type: Drug
intervention name: Nazartinib
description: Capsule for oral use; 25 mg, 50 mg; once a day
arm group label: Capmatinib + Nazartinib
other name: EGF816
intervention type: Drug
intervention name: Gefitinib
description: tablets for oral use; 250mg; once a day
arm group label: Capmatinib + Gefitinib
intervention type: Drug
intervention name: Osimertinib
description: Tablets for oral use; 40 mg, 80 mg; once a day.
arm group label: Capmatinib + Osimertinib
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Toni Wozniak, MD
role: Principal Investigator
affiliation: Barbara Ann Karmanos Cancer Institute
last name: Novartis Pharmaceuticals
phone: 1-888-669-6682
email: Novartis.email@novartis.com
last name: Novartis Pharmaceuticals
phone: +41613241111
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Completed
facility: 
status: Completed
facility: 
status: Withdrawn
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Withdrawn
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Completed
country: Belgium
country: Canada
country: Denmark
country: France
country: Germany
country: Italy
country: Korea, Republic of
country: Singapore
country: Spain
country: United States
responsible party type: Sponsor
mesh term: Gefitinib
mesh term: Osimertinib
mesh term: Nazartinib
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