<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/NCT02258607</url>
  </required_header>
  <id_info>
    <org_study_id>GS-US-370-1297</org_study_id>
    <nct_id>NCT02258607</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Momelotinib Combined With Trametinib in Adults With Metastatic KRAS-mutated Non-Small Cell Lung Cancer (NSCLC) Who Have Failed Platinum-Based Chemotherapy Preceded by a Dose-finding Lead-in Phase</brief_title>
  <official_title>A Phase 1b With Expansion Study Evaluating the Efficacy and Safety of Momelotinib Combined With Trametinib in Subjects With Metastatic KRAS-mutated Non-Small Cell Lung Cancer (NSCLC) Who Have Failed Platinum-Based Chemotherapy Preceded by a Dose-finding Lead-in Phase</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 is conducted in two phases. The Dose-finding Lead-in Phase, Part A, will evaluate&#xD;
      the safety and determine the maximum tolerated dose (MTD) of momelotinib (MMB) when combined&#xD;
      with trametinib. Once the MTD of momelotinib (MMB) is determined, the study will proceed to&#xD;
      the Dose-finding Lead-in Phase, Part B, to determine the MTD of trametinib. After the MTD is&#xD;
      established, the study may proceed to an expansion phase to determine the efficacy, safety,&#xD;
      and tolerability of MMB combined with trametinib at the MTD in participants with kirsten rat&#xD;
      sarcoma viral oncogene homolog (KRAS) mutated metastatic non-small cell lung cancer (NSCLC).&#xD;
      Each treatment cycle will consist of 28 days and treatment will continue in the absence of&#xD;
      disease progression, unacceptable toxicity, consent withdrawal, or participant's refusal of&#xD;
      treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <start_date type="Actual">March 11, 2015</start_date>
  <completion_date type="Actual">February 27, 2017</completion_date>
  <primary_completion_date type="Actual">July 19, 2016</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>For the Dose-finding Lead-in Phase, incidence of dose limiting toxicities (DLTs)</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Dose limiting toxicities (DLTs) refer to toxicities experienced during the first 28 days of treatment that have been judged to be clinically significant and at least possibly related to study treatment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>For Expansion Phase, disease control rate (DCR) at Week 8</measure>
    <time_frame>Week 8</time_frame>
    <description>Disease control rate (DCR) is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) or stable disease (SD) as assessed by Response Evaluation Criteria In Solid Tumor (RECIST) v1.1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>For the Dose-finding Lead-in Phase, disease control rate (DCR) at Week 8</measure>
    <time_frame>Week 8</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>For the Dose-finding Lead-in Phase, overall survival</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Overall survival is defined as the interval from first dose of study drug to death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>For the Dose-finding Lead-in Phase, progression free survival (PFS)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Progression free survival (PFS) is defined as the interval from first dose date of study drug to the earlier of the first documentation of definitive disease progression or death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>For the Dose-finding Lead-in Phase, overall response rate (ORR)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Overall response rate (ORR) is defined as the proportion of participants who achieve a CR or PR as assessed by RECIST v1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>For the Dose-finding Lead-in Phase, plasma pharmacokinetics (PK) parameters of momelotinib (MMB) and major metabolite GS-644603 as measured by Cmax and AUCtau</measure>
    <time_frame>Days 1 and 15 (Cycle 1 only)</time_frame>
    <description>This composite endpoint will measure the plasma PK profile of momelotinib (MMB) and GS-644603. The following parameters will be measured:&#xD;
Cmax: maximum observed concentration of drug in plasma&#xD;
AUCtau: concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>For Expansion Phase, overall survival</measure>
    <time_frame>Up to 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>For Expansion Phase, progression free survival (PFS)</measure>
    <time_frame>Up to 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>For Expansion Phase, overall response rate (ORR)</measure>
    <time_frame>Up to 2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Relapsed Metastatic KRAS-Mutated Non-Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Momelotinib (MMB) dose escalation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive momelotinib (MMB) plus trametinib. Momelotinib (MMB) dose will increase to find the MTD.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Trametinib dose escalation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive momelotinib (MMB) plus trametinib. Trametinib dose will increase to find the MTD.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Momelotinib (MMB)+trametinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Expansion Phase: participants will receive momelotinib (MMB) plus trametinib for the duration of the study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Momelotinib (MMB)</intervention_name>
    <description>Momelotinib (MMB) tablet(s) administered orally once or twice daily</description>
    <arm_group_label>Momelotinib (MMB) dose escalation</arm_group_label>
    <arm_group_label>Momelotinib (MMB)+trametinib</arm_group_label>
    <arm_group_label>Trametinib dose escalation</arm_group_label>
    <other_name>GS-0387</other_name>
    <other_name>CYT387</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trametinib</intervention_name>
    <description>Trametinib tablet administered orally once daily</description>
    <arm_group_label>Momelotinib (MMB) dose escalation</arm_group_label>
    <arm_group_label>Momelotinib (MMB)+trametinib</arm_group_label>
    <arm_group_label>Trametinib dose escalation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Individuals with KRAS-mutated metastatic or recurrent non-small cell lung cancer&#xD;
&#xD;
          -  Radiologic documentation of disease progression&#xD;
&#xD;
          -  Measurable disease per RECIST v1.1&#xD;
&#xD;
          -  Adequate organ function defined as follows:&#xD;
&#xD;
               -  Hepatic: Total conjugated bilirubin ≤ 1.25 x upper limit of normal (ULN);&#xD;
                  aspartate transaminase (AST) and alanine transaminase (ALT) &lt; 3 x upper limit of&#xD;
                  normal (ULN) or &lt; 5 x ULN in the setting of liver metastases&#xD;
&#xD;
          -  Hematological: Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L, platelet ≥ 100 x&#xD;
             10^9/L, hemoglobin ≥ 9 g/dL&#xD;
&#xD;
               -  Renal: Serum creatinine &lt; 1.5 x ULN OR calculated creatinine clearance (CLcr) ≥&#xD;
                  60 ml/min&#xD;
&#xD;
          -  Adequate left ventricular ejection fraction (LVEF) ≥ 50%&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1&#xD;
&#xD;
          -  Negative serum pregnancy test for females&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Less than or equal to 3 weeks since receiving treatment with biologic, small molecule,&#xD;
             chemotherapy or other agent for non-small cell lung cancer and 28 days since any prior&#xD;
             immunotherapy (such as nivolumab)&#xD;
&#xD;
          -  History of a concurrent or second malignancy, except for specified exceptions in the&#xD;
             protocol or any other cancer that has been in complete remission for ≥ 5 years&#xD;
&#xD;
          -  Known positive status for human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Chronic active or acute viral hepatitis A, B, or C infection or hepatitis B or C&#xD;
             carrier&#xD;
&#xD;
          -  Presence of ≥ Grade 2 peripheral neuropathy&#xD;
&#xD;
          -  Brain metastases, or spinal cord compression. Individuals with brain metastases are&#xD;
             allowed if they have been treated with irradiation or surgery, are clinically stable&#xD;
             without steroid treatment. Individuals with documented leptomeningeal disease are not&#xD;
             eligible&#xD;
&#xD;
          -  A history of uveitis and/or scleritis&#xD;
&#xD;
          -  Retinal pathology beyond normal age-related processes&#xD;
&#xD;
          -  Evidence of a retinal vein occlusion on ophthalmological exam or a history of retinal&#xD;
             vein occlusion&#xD;
&#xD;
          -  History of newly diagnosed or uncontrolled glaucoma/intraocular pressure &gt; 21 mm Hg as&#xD;
             measured by tonography&#xD;
&#xD;
          -  Use of daily and/or chronic oral or ocular steroids. Individuals must be off daily&#xD;
             steroids for at least 3 weeks prior to enrolling into the trial&#xD;
&#xD;
          -  History of interstitial pneumonitis&#xD;
&#xD;
          -  History of long QT syndrome or whose corrected QT interval (QTc) measured (Fridericia&#xD;
             method) at screening is prolonged (&gt; 480 ms for males and females)&#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>Sacramento</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Fairfax</city>
        <state>Virginia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Spokane</city>
        <state>Washington</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>October 3, 2014</study_first_submitted>
  <study_first_submitted_qc>October 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 7, 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>Lung Neoplasms</mesh_term>
    <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>Trametinib</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/NCT02258607
org study id: GS-US-370-1297
nct id: NCT02258607
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study is conducted in two phases. The Dose-finding Lead-in Phase, Part A, will evaluate
      the safety and determine the maximum tolerated dose (MTD) of momelotinib (MMB) when combined
      with trametinib. Once the MTD of momelotinib (MMB) is determined, the study will proceed to
      the Dose-finding Lead-in Phase, Part B, to determine the MTD of trametinib. After the MTD is
      established, the study may proceed to an expansion phase to determine the efficacy, safety,
      and tolerability of MMB combined with trametinib at the MTD in participants with kirsten rat
      sarcoma viral oncogene homolog (KRAS) mutated metastatic non-small cell lung cancer (NSCLC).
      Each treatment cycle will consist of 28 days and treatment will continue in the absence of
      disease progression, unacceptable toxicity, consent withdrawal, or participant's refusal of
      treatment.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: For the Dose-finding Lead-in Phase, incidence of dose limiting toxicities (DLTs)
time frame: Up to 28 days
description: Dose limiting toxicities (DLTs) refer to toxicities experienced during the first 28 days of treatment that have been judged to be clinically significant and at least possibly related to study treatment.
measure: For Expansion Phase, disease control rate (DCR) at Week 8
time frame: Week 8
description: Disease control rate (DCR) is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) or stable disease (SD) as assessed by Response Evaluation Criteria In Solid Tumor (RECIST) v1.1.
measure: For the Dose-finding Lead-in Phase, disease control rate (DCR) at Week 8
time frame: Week 8
measure: For the Dose-finding Lead-in Phase, overall survival
time frame: Up to 2 years
description: Overall survival is defined as the interval from first dose of study drug to death from any cause.
measure: For the Dose-finding Lead-in Phase, progression free survival (PFS)
time frame: Up to 2 years
description: Progression free survival (PFS) is defined as the interval from first dose date of study drug to the earlier of the first documentation of definitive disease progression or death from any cause.
measure: For the Dose-finding Lead-in Phase, overall response rate (ORR)
time frame: Up to 2 years
description: Overall response rate (ORR) is defined as the proportion of participants who achieve a CR or PR as assessed by RECIST v1.1.
measure: For the Dose-finding Lead-in Phase, plasma pharmacokinetics (PK) parameters of momelotinib (MMB) and major metabolite GS-644603 as measured by Cmax and AUCtau
time frame: Days 1 and 15 (Cycle 1 only)
description: This composite endpoint will measure the plasma PK profile of momelotinib (MMB) and GS-644603. The following parameters will be measured:
Cmax: maximum observed concentration of drug in plasma
AUCtau: concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)
measure: For Expansion Phase, overall survival
time frame: Up to 2 years
measure: For Expansion Phase, progression free survival (PFS)
time frame: Up to 2 years
measure: For Expansion Phase, overall response rate (ORR)
time frame: Up to 2 years
arm group label: Momelotinib (MMB) dose escalation
arm group type: Experimental
description: Participants will receive momelotinib (MMB) plus trametinib. Momelotinib (MMB) dose will increase to find the MTD.
arm group label: Trametinib dose escalation
arm group type: Experimental
description: Participants will receive momelotinib (MMB) plus trametinib. Trametinib dose will increase to find the MTD.
arm group label: Momelotinib (MMB)+trametinib
arm group type: Experimental
description: Expansion Phase: participants will receive momelotinib (MMB) plus trametinib for the duration of the study.
intervention type: Drug
intervention name: Momelotinib (MMB)
description: Momelotinib (MMB) tablet(s) administered orally once or twice daily
arm group label: Momelotinib (MMB) dose escalation
arm group label: Momelotinib (MMB)+trametinib
arm group label: Trametinib dose escalation
other name: GS-0387
other name: CYT387
intervention type: Drug
intervention name: Trametinib
description: Trametinib tablet administered orally once daily
arm group label: Momelotinib (MMB) dose escalation
arm group label: Momelotinib (MMB)+trametinib
arm group label: Trametinib dose escalation
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: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Trametinib
mesh term: N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide