<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/NCT02205398</url>
  </required_header>
  <id_info>
    <org_study_id>CINC280X2104</org_study_id>
    <secondary_id>2014-000579-20</secondary_id>
    <nct_id>NCT02205398</nct_id>
  </id_info>
  <brief_title>Study of Safety and Efficacy of INC280 and Cetuximab, in Adult c-MET Positive mCRC and HNSCC Patients After Progression on Cetuximab or Panitumumab Therapy</brief_title>
  <official_title>A Phase Ib, Open-label, Multicenter, Dose Escalation and Expansion Study, to Evaluate the Safety, Pharmacokinetics and Activity of INC280 in Combination With Cetuximab in c-MET Positive CRC and HNSCC Patients Who Have Progressed After Anti-EGFR Monoclonal Antibody Therapy.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This was an open-label, phase Ib, multicenter clinical trial to determine the MTD/RDE of the&#xD;
      orally administered c-MET inhibitor INC280 in combination with cetuximab. This combination&#xD;
      was to be explored in c-MET positive mCRC and HNSCC patients whose disease progressed on&#xD;
      cetuximab or panitumumab treatment. The dose escalation part was to be guided by a Bayesian&#xD;
      Logistic Regression Model with overdose control. At MTD/RDE, additional mCRC and HNSCC&#xD;
      patients who progressed on cetuximab or panitumumab treatment were to be enrolled in two&#xD;
      expansion groups to further assess the anti-tumor activity and the safety and tolerability of&#xD;
      the combination of INC280 and cetuximab. Patients were to receive INC280 on a continuous bid&#xD;
      dosing regimen and cetuximab every week. A treatment cycle was defined as 28 days with no&#xD;
      scheduled break between cycles.&#xD;
&#xD;
      The trial was terminated because of difficulties in identifying patients who met the&#xD;
      eligibility criteria.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <start_date type="Actual">July 28, 2014</start_date>
  <completion_date type="Actual">January 20, 2017</completion_date>
  <primary_completion_date type="Actual">January 20, 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Dose Limiting Toxicities (DLTs)</measure>
    <time_frame>during Cycle 1 and up to 4 weeks from the time of study treatment start</time_frame>
    <description>To estimate the MTD and/or RDE of INC280 in combination with cetuximab in c-MET positive mCRC and HNSCC patients as measured by the incidence of DLTs in Cycle 1. A treatment cycle was defined as 28 days with no scheduled break between cycles.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Frequency of Adverse Events (AEs)/Serious Adverse Events (SAEs)</measure>
    <time_frame>During Cycle 1 Day 1 (C1D1) until treatment discontinuation for up to 2 years</time_frame>
    <description>To characterize the safety and tolerability of the INC280 and cetuximab combination as measured by the frequency of AEs/SAEs in patients treated with the combination of INC280 and cetuximab</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate</measure>
    <time_frame>Every 8 weeks from cycle 1, day 1 until the end of study for up to 3 years</time_frame>
    <description>To assess preliminary anti-tumor activity of the INC280 and cetuximab combination as measured by Overall Response Rate in patients treated with the combination of INC280 and cetuximab. The end of study was upon completion of the survival follow-up period of the last patient treated with the combination of INC280 and cetuximab. A treatment cycle was defined as 28 days with no scheduled break between cycles.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Every 12 weeks until the end of study for up to 3 years</time_frame>
    <description>To assess additional clinical activity of the INC280 and cetuximab combination as measured by Overall Survival for patients in the expansion part of the study. The end of study was upon completion of the survival follow-up period of the last patient treated with the combination of INC280 and cetuximab.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time versus plasma concentration profiles and basic PK parameters of INC280</measure>
    <time_frame>during the first 4 Cycles of treatment or up to 16 weeks from the time of study treatment start</time_frame>
    <description>To characterize the PK profile of INC280 with cetuximab combination as measured by time versus plasma concentration profiles and basic PK parameters of INC280. A treatment cycle was defined as 28 days with no scheduled break between cycles.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of Adverse Events (AEs)/Serious Adverse Events (SAEs)</measure>
    <time_frame>From Cycle 1 Day 1 until treatment discontinuation for up to 2 years</time_frame>
    <description>To characterize the safety and tolerability of the INC280 and cetuximab combination as measured by severity of AEs/SAEs in patients treated with the combination of INC280 and cetuximab</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of dose treatment interruptions and reductions</measure>
    <time_frame>From Cycle 1 Day 1 until treatment discontinuation for up to 2 years</time_frame>
    <description>To characterize the safety and tolerability of the INC280 and cetuximab combination as measured by the frequency of dose interruptions and dose reductions in patients treated with the combination of INC280 and cetuximab</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>Every 8 weeks from C1D1 until the end of study for up to 3 years</time_frame>
    <description>To assess preliminary anti-tumor activity of the INC280 and cetuximab combination as measured by Progression Free Survival in patients treated with the combination of INC280 and cetuximab.The end of study was upon completion of the survival follow-up period of the last patient treated with the combination of INC280 and cetuximab.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Squamous Cell Carcinoma of Head and Neck (SCCHN)</condition>
  <condition>Metastatic Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>c-MET positive mCRC and HNSCC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>c-MET positive and K/NRAS WT mCRC and c-MET positive HNSCC patients</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>INC280</intervention_name>
    <arm_group_label>c-MET positive mCRC and HNSCC</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>cetuximab</intervention_name>
    <arm_group_label>c-MET positive mCRC and HNSCC</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female aged ≥ 18 years&#xD;
&#xD;
          -  Metastatic colorectal cancer or head and neck squamous cell carcinoma&#xD;
&#xD;
          -  c-MET positive (defined by c-MET IHC intensity score +2 in ≥ 50% of tumor cells and&#xD;
             MET gene copy number ≥ 5 by FISH or IHC intensity score +3 in ≥ 50% of tumor cells)&#xD;
             and K/NRAS WT status for mCRC patients only&#xD;
&#xD;
          -  At least one previous line of treatment for the metastatic disease and the last&#xD;
             treatment must have included cetuximab or panitumumab. Documentation of clinical&#xD;
             benefit and subsequent progression on cetuximab or panitumumab as the most recent line&#xD;
             of treatment is required for patients in the expansion part&#xD;
&#xD;
          -  Measurable disease as per RECIST v1.1&#xD;
&#xD;
          -  ECOG performance status ≤ 2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior treatment with c-MET/HGF inhibitors&#xD;
&#xD;
          -  History of severe reactions to cetuximab and/or panitumumab (except for G3 rash and G3&#xD;
             hypomagnesaemia)&#xD;
&#xD;
          -  History of acute or chronic pancreatitis&#xD;
&#xD;
          -  Active bleeding within 4 weeks prior to screening visit&#xD;
&#xD;
          -  Symptomatic brain metastases&#xD;
&#xD;
          -  Feeding tube dependence&#xD;
&#xD;
          -  Not adequate hematologic, renal and hepatic function&#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>Massachusetts General Hospital Head &amp; Neck</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering MSKCC NY</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10017</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah / Huntsman Cancer Institute Onc Dept</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <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>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1X6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lyon Cedex</city>
        <zip>69373</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Toulouse Cedex 9</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Essen</city>
        <zip>45147</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Wuerzburg</city>
        <zip>97080</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ancona</city>
        <state>AN</state>
        <zip>60126</zip>
        <country>Italy</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>Barcelona</city>
        <state>Catalunya</state>
        <zip>08003</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>Hospitalet de LLobregat</city>
        <state>Catalunya</state>
        <zip>08907</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Valencia</city>
        <state>Comunidad Valenciana</state>
        <zip>46010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Canada</country>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>July 25, 2014</study_first_submitted>
  <study_first_submitted_qc>July 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 31, 2014</study_first_posted>
  <last_update_submitted>January 17, 2019</last_update_submitted>
  <last_update_submitted_qc>January 17, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 22, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>INC280</keyword>
  <keyword>c-MET inhibitor</keyword>
  <keyword>cetuximab</keyword>
  <keyword>metastatic colorectal cancer</keyword>
  <keyword>head and neck</keyword>
  <keyword>squamous cell carcinoma</keyword>
  <keyword>resistance to cetuximab/panitumumab</keyword>
  <keyword>SCCHN,</keyword>
  <keyword>cancer</keyword>
  <keyword>oral and nasal cavity</keyword>
  <keyword>paranasal sinuses</keyword>
  <keyword>pharynx</keyword>
  <keyword>larynx</keyword>
  <keyword>parotid glands</keyword>
  <keyword>lympth nodes of neck</keyword>
  <keyword>mucosal lining</keyword>
  <keyword>epithelium</keyword>
  <keyword>colon</keyword>
  <keyword>large intestine</keyword>
  <keyword>rectal cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cetuximab</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02205398
org study id: CINC280X2104
secondary id: 2014-000579-20
nct id: NCT02205398
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This was an open-label, phase Ib, multicenter clinical trial to determine the MTD/RDE of the
      orally administered c-MET inhibitor INC280 in combination with cetuximab. This combination
      was to be explored in c-MET positive mCRC and HNSCC patients whose disease progressed on
      cetuximab or panitumumab treatment. The dose escalation part was to be guided by a Bayesian
      Logistic Regression Model with overdose control. At MTD/RDE, additional mCRC and HNSCC
      patients who progressed on cetuximab or panitumumab treatment were to be enrolled in two
      expansion groups to further assess the anti-tumor activity and the safety and tolerability of
      the combination of INC280 and cetuximab. Patients were to receive INC280 on a continuous bid
      dosing regimen and cetuximab every week. A treatment cycle was defined as 28 days with no
      scheduled break between cycles.

      The trial was terminated because of difficulties in identifying patients who met the
      eligibility criteria.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of Dose Limiting Toxicities (DLTs)
time frame: during Cycle 1 and up to 4 weeks from the time of study treatment start
description: To estimate the MTD and/or RDE of INC280 in combination with cetuximab in c-MET positive mCRC and HNSCC patients as measured by the incidence of DLTs in Cycle 1. A treatment cycle was defined as 28 days with no scheduled break between cycles.
measure: Frequency of Adverse Events (AEs)/Serious Adverse Events (SAEs)
time frame: During Cycle 1 Day 1 (C1D1) until treatment discontinuation for up to 2 years
description: To characterize the safety and tolerability of the INC280 and cetuximab combination as measured by the frequency of AEs/SAEs in patients treated with the combination of INC280 and cetuximab
measure: Overall Response Rate
time frame: Every 8 weeks from cycle 1, day 1 until the end of study for up to 3 years
description: To assess preliminary anti-tumor activity of the INC280 and cetuximab combination as measured by Overall Response Rate in patients treated with the combination of INC280 and cetuximab. The end of study was upon completion of the survival follow-up period of the last patient treated with the combination of INC280 and cetuximab. A treatment cycle was defined as 28 days with no scheduled break between cycles.
measure: Overall Survival
time frame: Every 12 weeks until the end of study for up to 3 years
description: To assess additional clinical activity of the INC280 and cetuximab combination as measured by Overall Survival for patients in the expansion part of the study. The end of study was upon completion of the survival follow-up period of the last patient treated with the combination of INC280 and cetuximab.
measure: Time versus plasma concentration profiles and basic PK parameters of INC280
time frame: during the first 4 Cycles of treatment or up to 16 weeks from the time of study treatment start
description: To characterize the PK profile of INC280 with cetuximab combination as measured by time versus plasma concentration profiles and basic PK parameters of INC280. A treatment cycle was defined as 28 days with no scheduled break between cycles.
measure: Severity of Adverse Events (AEs)/Serious Adverse Events (SAEs)
time frame: From Cycle 1 Day 1 until treatment discontinuation for up to 2 years
description: To characterize the safety and tolerability of the INC280 and cetuximab combination as measured by severity of AEs/SAEs in patients treated with the combination of INC280 and cetuximab
measure: Frequency of dose treatment interruptions and reductions
time frame: From Cycle 1 Day 1 until treatment discontinuation for up to 2 years
description: To characterize the safety and tolerability of the INC280 and cetuximab combination as measured by the frequency of dose interruptions and dose reductions in patients treated with the combination of INC280 and cetuximab
measure: Progression Free Survival
time frame: Every 8 weeks from C1D1 until the end of study for up to 3 years
description: To assess preliminary anti-tumor activity of the INC280 and cetuximab combination as measured by Progression Free Survival in patients treated with the combination of INC280 and cetuximab.The end of study was upon completion of the survival follow-up period of the last patient treated with the combination of INC280 and cetuximab.
arm group label: c-MET positive mCRC and HNSCC
arm group type: Experimental
description: c-MET positive and K/NRAS WT mCRC and c-MET positive HNSCC patients
intervention type: Drug
intervention name: INC280
arm group label: c-MET positive mCRC and HNSCC
intervention type: Drug
intervention name: cetuximab
arm group label: c-MET positive mCRC and HNSCC
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Belgium
country: Canada
country: France
country: Germany
country: Italy
country: Spain
country: United States
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Carcinoma, Squamous Cell
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Cetuximab