<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/NCT03810872</url>
  </required_header>
  <id_info>
    <org_study_id>Precision 2 - 1200.264</org_study_id>
    <nct_id>NCT03810872</nct_id>
  </id_info>
  <brief_title>An Explorative Study of Afatinib in the Treatment of Advanced Cancer Carrying an EGFR, a HER2 or a HER3 Mutation</brief_title>
  <official_title>An Open Explorative Phase II, Open Label Study of Afatinib in the Treatment of Advanced Cancer Carrying an EGFR, a HER2 or a HER3 Mutation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AZ-VUB</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AZ-VUB</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Objective(s):To investigate the efficacy and safety of afatinib in EGFR, HER 2 and HER3&#xD;
      mutated cancers, regardless of cancer type, excluding EGFR mutated non-small cell lung&#xD;
      cancer.&#xD;
&#xD;
      Methodology:Open label, genomic driven trial (basket trial)&#xD;
&#xD;
      No. of patients total entered:Optimal Simon two stage design for the three genetic driven&#xD;
      cohorts: 10 patients will be enrolled per cancer type in the first stage and an additional 19&#xD;
      in the second stage (maximum total 87 patients)&#xD;
&#xD;
      Indication : cancers harbouring an EGFR mutation(excluding non-squamous non- small cell lung&#xD;
      cancer, a registered indication), a HER2 mutation or a HER3 mutation&#xD;
&#xD;
      Test product(s) : Afatinib At progression paclitaxel will be added for those patients that&#xD;
      have no contra-indications&#xD;
&#xD;
      dose: Starting dose of afatinib at 40 mg/day. Dose increase to 50 mg in the absence of&#xD;
      adverse events. Stepwise dose reduction to 30,20, 10 mg/day according to drug-related adverse&#xD;
      events.&#xD;
&#xD;
      At progression, addition of paclitaxel 80 mg/m2 weekly 3w/4 to afatinib 40 mg/day .&#xD;
&#xD;
      mode of admin. : Oral for afatinib Intravenous for paclitaxel&#xD;
&#xD;
      Duration of treatment: Continuous treatment until progression or unacceptable adverse events&#xD;
      or withdrawal of consent.&#xD;
&#xD;
      At disease progression, add paclitaxel until progression or unacceptable adverse event or&#xD;
      withdrawal of consent if no contra-indications.&#xD;
&#xD;
      Criteria for efficacy: Primary Endpoint:&#xD;
&#xD;
      • Response rate (CR+ PR) via RECIST v1.1&#xD;
&#xD;
      Secondary Endpoints:&#xD;
&#xD;
        -  Disease control rate (CR+PR+SD)&#xD;
&#xD;
        -  Progression free survival&#xD;
&#xD;
        -  Overall survival&#xD;
&#xD;
        -  To correlate tumor response with findings on tumor biopsies&#xD;
&#xD;
        -  To investigate resistance mechanisms&#xD;
&#xD;
        -  response rate (CR+ PR) determined by RECIST and progression free survival on the&#xD;
           combination therapy of afatinib and paclitaxel&#xD;
&#xD;
      Criteria for safety: Incidence and intensity of adverse events according CTCAE v4.0&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 21, 2017</start_date>
  <completion_date type="Anticipated">December 2022</completion_date>
  <primary_completion_date type="Anticipated">December 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Response rate</measure>
    <time_frame>6 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence and intensity of adverse events</measure>
    <time_frame>4 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease control rate</measure>
    <time_frame>6 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>6 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>6 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">87</enrollment>
  <condition>Cancers Harbouring an EGFR Mutation, (Excluding Non-squamous Non- Small Cell Lung Cancer, a Registered Indication), a HER2 Mutation or a HER3 Mutation</condition>
  <arm_group>
    <arm_group_label>Open label</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Afatinib 40 mg/day during Period 1 Afatinib 40 mg/day + Paclitaxel 80mg/kg/3w during Period 2</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Afatinib</intervention_name>
    <description>Open label</description>
    <arm_group_label>Open label</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>Paclitaxel</description>
    <arm_group_label>Open label</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women and men with locally advanced or metastatic cancers harboring either an&#xD;
             activating EGFR mutation or a HER2 mutation or a HER3 mutation&#xD;
&#xD;
          -  Failure of at least one line of standard systemic therapy&#xD;
&#xD;
          -  No eligibility for other open genomic driven phase I, II or III trial available for&#xD;
             these tumor genotypes&#xD;
&#xD;
          -  ECOG performance status ≤2&#xD;
&#xD;
          -  Patient with a life expectancy &gt;3 months&#xD;
&#xD;
          -  Patients able to provide written informed consent prior to enrollment into the&#xD;
             clinical trial.&#xD;
&#xD;
          -  Adequate organ function&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Non squamous non-small cell lung cancer harbouring an EGFR mutation (registered&#xD;
             indication)&#xD;
&#xD;
          -  Chemotherapy, biological therapy or investigational agents within four weeks prior to&#xD;
             the start of study treatment&#xD;
&#xD;
          -  Known hypersensitivity to afatinib or the excipients of any of the trial drugs&#xD;
&#xD;
          -  Prior treatment with afatinib&#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_contact>
    <last_name>Lore Decoster, Dr</last_name>
    <phone>+32 2 477 64 15</phone>
    <email>lore.decoster@uzbrussel.be</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Nadia Cappoen</last_name>
    <phone>+32 2 477 54 81</phone>
    <email>nadia.cappoen@uzbrussel.be</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Institut Jules Bordet</name>
      <address>
        <city>Brussels</city>
        <zip>1000</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michel Dubuisson</last_name>
    </contact>
    <investigator>
      <last_name>Philippe Aftimos, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Les Cliniques Universitaires St Luc</name>
      <address>
        <city>Brussels</city>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>jean-Pascal Machiels, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Universitaire Ziekenhuis Antwerpen</name>
      <address>
        <city>Edegem</city>
        <zip>2650</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Robrecht Lembrechts</last_name>
      <phone>+32 3 821 55 80</phone>
      <email>robrecht.lembrechts@uza.be</email>
    </contact>
    <investigator>
      <last_name>Christian Rolfo, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UZ Gent</name>
      <address>
        <city>Gent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ann Clue</last_name>
      <email>ann.clue@uzgent.be</email>
    </contact>
    <investigator>
      <last_name>Sylvie Rottey, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Sart-Tilman</name>
      <address>
        <city>Liège</city>
        <zip>4000</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Maude Piron</last_name>
      <phone>+32 4 366 82 50</phone>
      <email>mpiron@chu.ulg.ac.be</email>
    </contact>
    <investigator>
      <last_name>Joelle Collignon, Dr</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 12, 2019</study_first_submitted>
  <study_first_submitted_qc>January 18, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 22, 2019</study_first_posted>
  <last_update_submitted>January 18, 2019</last_update_submitted>
  <last_update_submitted_qc>January 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 22, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>AZ-VUB</investigator_affiliation>
    <investigator_full_name>Dr. Lore Decoster</investigator_full_name>
    <investigator_title>Coordinator Investigator</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Afatinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03810872
org study id: Precision 2 - 1200.264
nct id: NCT03810872
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Objective(s):To investigate the efficacy and safety of afatinib in EGFR, HER 2 and HER3
      mutated cancers, regardless of cancer type, excluding EGFR mutated non-small cell lung
      cancer.

      Methodology:Open label, genomic driven trial (basket trial)

      No. of patients total entered:Optimal Simon two stage design for the three genetic driven
      cohorts: 10 patients will be enrolled per cancer type in the first stage and an additional 19
      in the second stage (maximum total 87 patients)

      Indication : cancers harbouring an EGFR mutation(excluding non-squamous non- small cell lung
      cancer, a registered indication), a HER2 mutation or a HER3 mutation

      Test product(s) : Afatinib At progression paclitaxel will be added for those patients that
      have no contra-indications

      dose: Starting dose of afatinib at 40 mg/day. Dose increase to 50 mg in the absence of
      adverse events. Stepwise dose reduction to 30,20, 10 mg/day according to drug-related adverse
      events.

      At progression, addition of paclitaxel 80 mg/m2 weekly 3w/4 to afatinib 40 mg/day .

      mode of admin. : Oral for afatinib Intravenous for paclitaxel

      Duration of treatment: Continuous treatment until progression or unacceptable adverse events
      or withdrawal of consent.

      At disease progression, add paclitaxel until progression or unacceptable adverse event or
      withdrawal of consent if no contra-indications.

      Criteria for efficacy: Primary Endpoint:

      • Response rate (CR+ PR) via RECIST v1.1

      Secondary Endpoints:

        -  Disease control rate (CR+PR+SD)

        -  Progression free survival

        -  Overall survival

        -  To correlate tumor response with findings on tumor biopsies

        -  To investigate resistance mechanisms

        -  response rate (CR+ PR) determined by RECIST and progression free survival on the
           combination therapy of afatinib and paclitaxel

      Criteria for safety: Incidence and intensity of adverse events according CTCAE v4.0
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Response rate
time frame: 6 weeks
measure: Incidence and intensity of adverse events
time frame: 4 weeks
measure: Disease control rate
time frame: 6 weeks
measure: Progression free survival
time frame: 6 weeks
measure: Overall survival
time frame: 6 weeks
arm group label: Open label
arm group type: Other
description: Afatinib 40 mg/day during Period 1 Afatinib 40 mg/day + Paclitaxel 80mg/kg/3w during Period 2
intervention type: Drug
intervention name: Afatinib
description: Open label
arm group label: Open label
intervention type: Drug
intervention name: Paclitaxel
description: Paclitaxel
arm group label: Open label
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Lore Decoster, Dr
phone: +32 2 477 64 15
email: lore.decoster@uzbrussel.be
last name: Nadia Cappoen
phone: +32 2 477 54 81
email: nadia.cappoen@uzbrussel.be
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
investigator: 
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: Belgium
responsible party type: Principal Investigator
investigator affiliation: AZ-VUB
investigator full name: Dr. Lore Decoster
investigator title: Coordinator Investigator
mesh term: Paclitaxel
mesh term: Afatinib
sharing ipd: No