<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/NCT02206763</url>
  </required_header>
  <id_info>
    <org_study_id>GS-US-370-1298</org_study_id>
    <nct_id>NCT02206763</nct_id>
  </id_info>
  <brief_title>Erlotinib and Momelotinib for the Treatment of Epidermal Growth Factor Receptor (EGFR) Mutated EGFR Tyrosine Kinase Inhibitor (TKI) Naive Metastatic Non-Small Cell Lung Cancer (NSCLC)</brief_title>
  <official_title>A Phase 1b Study of Erlotinib and Momelotinib for the Treatment of Epidermal Growth Factor Receptor (EGFR) Mutated EGFR Tyrosine Kinase Inhibitor (TKI) Naïve Metastatic Non-Small Cell Lung Cancer (NSCLC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sierra Oncology LLC - a GSK company</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sierra Oncology LLC - a GSK company</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>
      This study will evaluate the safety, preliminary efficacy, and pharmacokinetics (PK) of&#xD;
      momelotinib (MMB) and erlotinib, as well as define the maximum tolerated dose (MTD) of&#xD;
      momelotinib (MMB) combined with erlotinib in adults with epidermal growth factor receptor&#xD;
      (EGFR)-mutated, EGFR tyrosine kinase inhibitor (TKI) naive metastatic non-small cell lung&#xD;
      cancer (NSCLC). Participants will be sequentially enrolled to receive progressively&#xD;
      increasing doses of momelotinib (MMB) in combination with erlotinib. Escalation of&#xD;
      momelotinib (MMB) doses will proceed to the MTD, defined as the highest tested dose&#xD;
      associated with dose-limiting toxicities (DLT) during the first 28 days of combined erlotinib&#xD;
      and momelotinib (MMB) treatment. There will be four dose levels and each treatment cycle will&#xD;
      consist of 28 days.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <start_date type="Actual">October 16, 2014</start_date>
  <completion_date type="Actual">February 16, 2017</completion_date>
  <primary_completion_date type="Actual">January 12, 2017</primary_completion_date>
  <phase>Phase 1</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>Incidence of Dose Limiting Toxicities (DLTs)</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Dose limiting toxicities refer to toxicities experienced during the first 28 days of combined erlotinib and momelotinib (MMB) treatment that have been judged to be clinically significant and related to study treatment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety as Assessed by the Incidence of Adverse Events (AEs)</measure>
    <time_frame>Up to 2 years plus 30 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety as Assessed by the Percentage of Participants Experiencing Treatment-Emergent Graded Lab Abnormalities (including Chemistry, Coagulation, Hematology, and Urinalysis)</measure>
    <time_frame>Up to 2 years plus 30 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from Baseline in Vital Signs</measure>
    <time_frame>Up to 2 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival</measure>
    <time_frame>Until disease progression (up to 2 years)</time_frame>
    <description>Progression-free survival is defined as the interval from first dose date of study drug (MMB/erlotinib) to the earlier of the first documentation of definitive disease progression or death from any cause; definitive disease progression is progression based on RECIST criteria v1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Until disease progression (up to 2 years)</time_frame>
    <description>Overall survival is defined as the interval from first dose date of study drug (MMB/erlotinib) to death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate</measure>
    <time_frame>Until disease progression (up to 2 years)</time_frame>
    <description>Overall response rate is defined as the proportion of participants who achieve a complete response or partial response.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic (PK) Parameter: Cmax of momelotinib (MMB)</measure>
    <time_frame>Predose and up to 24 hours postdose</time_frame>
    <description>Cmax is defined as the maximum observed concentration of drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK Parameter: AUCtau of momelotinib (MMB)</measure>
    <time_frame>Predose and up to 24 hours postdose</time_frame>
    <description>AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK Parameter: Cmax of Erlotinib</measure>
    <time_frame>Predose and up to 24 hours postdose</time_frame>
    <description>Cmax is defined as the maximum observed concentration of drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK Parameter: AUCtau of Erlotinib</measure>
    <time_frame>Predose and up to 24 hours postdose</time_frame>
    <description>AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>EGFR Mutated EGFR TKI Naive Metastatic NSCLC</condition>
  <arm_group>
    <arm_group_label>Momelotinib (MMB)+erlotinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive momelotinib (MMB) plus erlotinib.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Momelotinib (MMB)</intervention_name>
    <description>Tablet(s) administered orally once or twice daily</description>
    <arm_group_label>Momelotinib (MMB)+erlotinib</arm_group_label>
    <other_name>GS-0387</other_name>
    <other_name>CYT387</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Erlotinib</intervention_name>
    <description>Tablet(s) administered orally once daily.</description>
    <arm_group_label>Momelotinib (MMB)+erlotinib</arm_group_label>
    <other_name>Tarceva®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Metastatic NSCLC with documented EGFR exon 19 deletion or exon 21 (L858R) substitution&#xD;
             mutation&#xD;
&#xD;
          -  Treatment naive OR one prior standard chemotherapy that is platinum-based&#xD;
&#xD;
          -  Adequate organ function defined as follows:&#xD;
&#xD;
               -  Hepatic: Total bilirubin &lt; upper limit of the normal range (ULN); aspartate&#xD;
                  transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN&#xD;
&#xD;
               -  Hematological: absolute neutrophil count (ANC) ≥1500 cells/mm^3, platelet ≥&#xD;
                  100,000 cells/mm^3, hemoglobin ≥ 9.0 g/dL&#xD;
&#xD;
               -  Renal: Serum creatinine &lt; ULN OR calculated creatinine clearance (CLcr) of ≥ 60&#xD;
                  ml/min&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Known positive status for human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Chronic active or acute viral hepatitis A, B, or C infection (testing required for&#xD;
             hepatitis B and C)&#xD;
&#xD;
          -  Presence of &gt; Grade 1 peripheral neuropathy&#xD;
&#xD;
          -  Symptomatic leptomeningeal, brain metastases, or spinal cord compression.&#xD;
&#xD;
          -  History of interstitial pneumonitis&#xD;
&#xD;
        Note: 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>Gilead Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Gilead Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Whittier</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>July 30, 2014</study_first_submitted>
  <study_first_submitted_qc>July 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 1, 2014</study_first_posted>
  <last_update_submitted>January 30, 2019</last_update_submitted>
  <last_update_submitted_qc>January 30, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 1, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>Erlotinib Hydrochloride</mesh_term>
    <mesh_term>N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide</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/NCT02206763
org study id: GS-US-370-1298
nct id: NCT02206763
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study will evaluate the safety, preliminary efficacy, and pharmacokinetics (PK) of
      momelotinib (MMB) and erlotinib, as well as define the maximum tolerated dose (MTD) of
      momelotinib (MMB) combined with erlotinib in adults with epidermal growth factor receptor
      (EGFR)-mutated, EGFR tyrosine kinase inhibitor (TKI) naive metastatic non-small cell lung
      cancer (NSCLC). Participants will be sequentially enrolled to receive progressively
      increasing doses of momelotinib (MMB) in combination with erlotinib. Escalation of
      momelotinib (MMB) doses will proceed to the MTD, defined as the highest tested dose
      associated with dose-limiting toxicities (DLT) during the first 28 days of combined erlotinib
      and momelotinib (MMB) treatment. There will be four dose levels and each treatment cycle will
      consist of 28 days.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of Dose Limiting Toxicities (DLTs)
time frame: Up to 28 days
description: Dose limiting toxicities refer to toxicities experienced during the first 28 days of combined erlotinib and momelotinib (MMB) treatment that have been judged to be clinically significant and related to study treatment.
measure: Safety as Assessed by the Incidence of Adverse Events (AEs)
time frame: Up to 2 years plus 30 days
measure: Safety as Assessed by the Percentage of Participants Experiencing Treatment-Emergent Graded Lab Abnormalities (including Chemistry, Coagulation, Hematology, and Urinalysis)
time frame: Up to 2 years plus 30 days
measure: Change from Baseline in Vital Signs
time frame: Up to 2 years
measure: Progression-Free Survival
time frame: Until disease progression (up to 2 years)
description: Progression-free survival is defined as the interval from first dose date of study drug (MMB/erlotinib) to the earlier of the first documentation of definitive disease progression or death from any cause; definitive disease progression is progression based on RECIST criteria v1.1.
measure: Overall Survival
time frame: Until disease progression (up to 2 years)
description: Overall survival is defined as the interval from first dose date of study drug (MMB/erlotinib) to death from any cause.
measure: Overall Response Rate
time frame: Until disease progression (up to 2 years)
description: Overall response rate is defined as the proportion of participants who achieve a complete response or partial response.
measure: Pharmacokinetic (PK) Parameter: Cmax of momelotinib (MMB)
time frame: Predose and up to 24 hours postdose
description: Cmax is defined as the maximum observed concentration of drug.
measure: PK Parameter: AUCtau of momelotinib (MMB)
time frame: Predose and up to 24 hours postdose
description: AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
measure: PK Parameter: Cmax of Erlotinib
time frame: Predose and up to 24 hours postdose
description: Cmax is defined as the maximum observed concentration of drug.
measure: PK Parameter: AUCtau of Erlotinib
time frame: Predose and up to 24 hours postdose
description: AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
arm group label: Momelotinib (MMB)+erlotinib
arm group type: Experimental
description: Participants will receive momelotinib (MMB) plus erlotinib.
intervention type: Drug
intervention name: Momelotinib (MMB)
description: Tablet(s) administered orally once or twice daily
arm group label: Momelotinib (MMB)+erlotinib
other name: GS-0387
other name: CYT387
intervention type: Drug
intervention name: Erlotinib
description: Tablet(s) administered orally once daily.
arm group label: Momelotinib (MMB)+erlotinib
other name: Tarceva®
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gilead Study Director
role: Study Director
affiliation: Gilead Sciences
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Erlotinib Hydrochloride
mesh term: N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide