<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/NCT02244489</url>
  </required_header>
  <id_info>
    <org_study_id>GS-US-370-1369</org_study_id>
    <nct_id>NCT02244489</nct_id>
  </id_info>
  <brief_title>Momelotinib Combined With Capecitabine and Oxaliplatin in Adults With Relapsed/Refractory Metastatic Pancreatic Ductal Adenocarcinoma</brief_title>
  <official_title>A Phase 1b Study Evaluating Momelotinib Combined With Capecitabine and Oxaliplatin in Subjects With Relapsed/Refractory Metastatic Pancreatic Ductal Adenocarcinoma</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, tolerability, and define the maximum tolerated dose&#xD;
      (MTD) of momelotinib (MMB) combined with capecitabine and oxaliplatin in adults with&#xD;
      relapsed/refractory metastatic pancreatic ductal adenocarcinoma.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <start_date type="Actual">November 5, 2014</start_date>
  <completion_date type="Actual">April 5, 2017</completion_date>
  <primary_completion_date type="Actual">March 8, 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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of dose limiting toxicities</measure>
    <time_frame>Up to 21 days</time_frame>
    <description>Dose limiting toxicities refer to toxicities experienced during the first 21 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>Incidence of adverse events, assessment of clinical laboratory test findings, physical examination, 12-lead electrocardiogram (ECG), and vital signs measurements</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>This composite endpoint will measure the safety profile of momelotinib.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response rate</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Overall response rate (ORR) is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) as assessed by the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Overall survival (OS) is defined as the interval from first dose date of study drug to death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</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; definitive disease progression is progression based on RECIST criteria v1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic (PK) profile of momelotinib (MMB)</measure>
    <time_frame>Predose and postdose on Day 15</time_frame>
    <description>This composite endpoint will measure the plasma PK profile of momelotinib (MMB). The following parameters will be measured, where applicable:&#xD;
Cmax: maximum observed concentration of drug in plasma&#xD;
Ctau: observed drug concentration at the end of the dosing interval&#xD;
AUCtau: concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Relapsed/Refractory Metastatic Pancreatic Ductal Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>Momelotinib (MMB)+capecitabine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive momelotinib (MMB)+capecitabine at varying dose levels to determine the MTD for momelotinib (MMB) and capecitabine.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Momelotinib (MMB)+capecitabine+oxaliplatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Upon reaching the MTD for momelotinib (MMB) and capecitabine or if no MTD is reached, participants will receive momelotinib (MMB)+capecitabine at the MTD plus oxaliplatin at varying dose levels to determine the MTD of combination capecitabine, momelotinib (MMB), and oxaliplatin.</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)+capecitabine</arm_group_label>
    <arm_group_label>Momelotinib (MMB)+capecitabine+oxaliplatin</arm_group_label>
    <other_name>GS-0387</other_name>
    <other_name>CYT387</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine</intervention_name>
    <description>Capecitabine tablet(s) administered orally twice daily for 14 days, followed by 7 days off, until the end of treatment</description>
    <arm_group_label>Momelotinib (MMB)+capecitabine</arm_group_label>
    <arm_group_label>Momelotinib (MMB)+capecitabine+oxaliplatin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxaliplatin</intervention_name>
    <description>Oxaliplatin administered intravenously over 120 minutes or as per institutional standard of care on Day 1 of each 21-day cycle.</description>
    <arm_group_label>Momelotinib (MMB)+capecitabine+oxaliplatin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Relapsed or refractory metastatic pancreatic adenocarcinoma&#xD;
&#xD;
          -  Received 1 prior chemotherapy regimen for metastatic pancreatic ductal adenocarcinoma&#xD;
             (not including neoadjuvant and/or adjuvant therapy)&#xD;
&#xD;
          -  Measurable disease per RECIST v1.1&#xD;
&#xD;
          -  Adequate organ function defined as&#xD;
&#xD;
               -  Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x upper limit of&#xD;
                  normal (ULN) OR ≤ 5 x ULN if liver metastases are present; total conjugated&#xD;
                  bilirubin ≤ 2 x ULN&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥1500 cells/mm^3, platelet ≥100,000 cells/mm^3,&#xD;
                  hemoglobin ≥ 9.0 g/dL&#xD;
&#xD;
               -  Creatinine clearance (CrCl) &gt; 50 ml/min as calculated by the Cockroft-Gault&#xD;
                  method&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Received more than 1 prior line of chemotherapy for metastatic pancreatic ductal&#xD;
             adenocarcinoma&#xD;
&#xD;
          -  Major surgery within 21 days of first dose of study drug&#xD;
&#xD;
          -  Minor surgical procedure(s) within 7 days of enrollment or not yet recovered from&#xD;
             prior minor surgery (placement of central venous access device, fine needle&#xD;
             aspiration, or endoscopic biliary stent ≥ 1 day before enrollment is acceptable)&#xD;
&#xD;
          -  Chemotherapy, immunotherapy, biologics, and/or investigational therapy within 21 days&#xD;
             prior to first dose of study drug&#xD;
&#xD;
          -  Known positive status for HIV, chronic active or acute viral hepatitis A, B, or C&#xD;
             infection, or hepatitis B or C carrier&#xD;
&#xD;
          -  Known dihydropyrimidine dehydrogenase deficiency&#xD;
&#xD;
          -  Peripheral neuropathy ≥ Grade 2&#xD;
&#xD;
          -  Any condition that impairs gastrointestinal absorption of drug&#xD;
&#xD;
          -  Known or suspected brain or central nervous system metastases&#xD;
&#xD;
          -  Diagnosis of pancreatic islet neoplasm, acinar cell carcinoma, non-adenocarcinoma,&#xD;
             adenocarcinoma originating from the biliary tree or cystadenocarcinoma&#xD;
&#xD;
          -  External biliary drain&#xD;
&#xD;
          -  Documented myocardial infarction or unstable/uncontrolled cardiac disease within 6&#xD;
             months of enrollment&#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>
      <name>Scottsdale Healthcare Research Institute</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85258</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cedars-Sinai Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Cancer Specialists, PC</name>
      <address>
        <city>Fairfax</city>
        <state>Virginia</state>
        <zip>22031</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>September 17, 2014</study_first_submitted>
  <study_first_submitted_qc>September 17, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 19, 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>Adenocarcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Capecitabine</mesh_term>
    <mesh_term>Oxaliplatin</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/NCT02244489
org study id: GS-US-370-1369
nct id: NCT02244489
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study will evaluate the safety, tolerability, and define the maximum tolerated dose
      (MTD) of momelotinib (MMB) combined with capecitabine and oxaliplatin in adults with
      relapsed/refractory metastatic pancreatic ductal adenocarcinoma.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of dose limiting toxicities
time frame: Up to 21 days
description: Dose limiting toxicities refer to toxicities experienced during the first 21 days of treatment that have been judged to be clinically significant and at least possibly related to study treatment.
measure: Incidence of adverse events, assessment of clinical laboratory test findings, physical examination, 12-lead electrocardiogram (ECG), and vital signs measurements
time frame: Up to 2 years
description: This composite endpoint will measure the safety profile of momelotinib.
measure: Overall response rate
time frame: Up to 2 years
description: Overall response rate (ORR) is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) as assessed by the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
measure: Overall survival
time frame: Up to 2 years
description: Overall survival (OS) is defined as the interval from first dose date of study drug to death from any cause.
measure: Progression-free survival
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; definitive disease progression is progression based on RECIST criteria v1.1.
measure: Pharmacokinetic (PK) profile of momelotinib (MMB)
time frame: Predose and postdose on Day 15
description: This composite endpoint will measure the plasma PK profile of momelotinib (MMB). The following parameters will be measured, where applicable:
Cmax: maximum observed concentration of drug in plasma
Ctau: observed drug concentration at the end of the dosing interval
AUCtau: concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)
arm group label: Momelotinib (MMB)+capecitabine
arm group type: Experimental
description: Participants will receive momelotinib (MMB)+capecitabine at varying dose levels to determine the MTD for momelotinib (MMB) and capecitabine.
arm group label: Momelotinib (MMB)+capecitabine+oxaliplatin
arm group type: Experimental
description: Upon reaching the MTD for momelotinib (MMB) and capecitabine or if no MTD is reached, participants will receive momelotinib (MMB)+capecitabine at the MTD plus oxaliplatin at varying dose levels to determine the MTD of combination capecitabine, momelotinib (MMB), and oxaliplatin.
intervention type: Drug
intervention name: Momelotinib (MMB)
description: Momelotinib (MMB) tablet(s) administered orally once or twice daily
arm group label: Momelotinib (MMB)+capecitabine
arm group label: Momelotinib (MMB)+capecitabine+oxaliplatin
other name: GS-0387
other name: CYT387
intervention type: Drug
intervention name: Capecitabine
description: Capecitabine tablet(s) administered orally twice daily for 14 days, followed by 7 days off, until the end of treatment
arm group label: Momelotinib (MMB)+capecitabine
arm group label: Momelotinib (MMB)+capecitabine+oxaliplatin
intervention type: Drug
intervention name: Oxaliplatin
description: Oxaliplatin administered intravenously over 120 minutes or as per institutional standard of care on Day 1 of each 21-day cycle.
arm group label: Momelotinib (MMB)+capecitabine+oxaliplatin
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: 
country: United States
responsible party type: Sponsor
mesh term: Adenocarcinoma
mesh term: Capecitabine
mesh term: Oxaliplatin
mesh term: N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide