<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/NCT01693419</url>
  </required_header>
  <id_info>
    <org_study_id>HMC-HO-GI-1201</org_study_id>
    <nct_id>NCT01693419</nct_id>
  </id_info>
  <brief_title>S-1, Gemcitabine and Erlotinib for Advanced Pancreatic Cancer</brief_title>
  <official_title>A Phase II Study of S-1 in Combination With Gemcitabine and Erlotinib in Patients With Advanced or Metastatic Pancreatic Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hallym University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Jeil Pharmaceutical Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Hallym University Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will conduct a phase II study of gemcitabine, erlotinib, and S-1 as first-line&#xD;
      chemotherapy in patients with advanced pancreatic cancer and evaluate the EGFR expression,&#xD;
      KRAS mutation, and BRAF mutation as predictive or prognostic markers&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Pancreatic ductal adenocarcinoma, also known as pancreatic cancer, is an eighth cause of&#xD;
      cancer-related deaths in the world. The estimated worldwide incidence of pancreatic cancer&#xD;
      was 277,000 cases and an estimated 266,000 patients died from the disease in 20081.&#xD;
&#xD;
      Pancreatic cancer is more common in elderly persons than in younger persons, and&#xD;
      characterised by early locoregional spread and distant metastasis. As a result, less than 20%&#xD;
      of patients are diagnosed with localized, potentially curable disease, and the median&#xD;
      survival is no longer than 3-4 months without effective treatment2.&#xD;
&#xD;
      Single-agent chemotherapy with gemcitabine was considered as standard of care for patients&#xD;
      with advanced pancreatic cancer, since Burris et al. demonstrated superiority of gemcitabine&#xD;
      over 5-fluorouracil (5-FU) in respect of a survival benefit as well as an improvement in&#xD;
      disease related symptoms in a randomized study3.&#xD;
&#xD;
      Nevertheless, the activity of gemcitabine monotherapy in pancreatic cancer was modest, and&#xD;
      there was a clear need to improve its efficacy by combining it with other anticancer drugs.&#xD;
&#xD;
      Multiple agents such as 5-FU4, capecitabine5,6, cisplatin7,8, oxaliplatin9, pemetrexed10,&#xD;
      irinotecan11, cetuximab12, and bevacizumab13, in combination with gemcitabine have been&#xD;
      tested in clinical trials, however, they have failed to improve the outcome.&#xD;
&#xD;
      The only agent that, in combination with gemcitabine, has shown a small, but statistically&#xD;
      significant improvement, with a hazard ratio (HR) of 0.82, the absolute improvement in median&#xD;
      overall survival (OS) of 5.9 months with gemcitabine versus 6.2 months with the combination,&#xD;
      is erlotinib, a small-molecule inhibitor of the epidermal growth factor receptor (EGFR)14.&#xD;
      Considering the modest improvement in survival by adding erlotinib to gemcitabine, new&#xD;
      combination therapy that have a great impact is urgently needed.&#xD;
&#xD;
      S-1 is an oral fluoropyrimidine derivative that combines tegafur (FT) with two modulators;&#xD;
      5-chloro-2, 4-dihydroxypyridine (CDHP) and oteracil potassium (Oxo) in a 1:0.4:1 molar&#xD;
      concentration ratio. The phase II trials of a combination of gemcitabine and S-1 have&#xD;
      demonstrated objective response rates of 32-48% and median survival of 8-12 months 15-17.&#xD;
&#xD;
      Therefore, we will conduct a phase II study of gemcitabine, erlotinib, and S-1 as first-line&#xD;
      chemotherapy in patients with advanced pancreatic cancer and evaluate the EGFR expression,&#xD;
      KRAS mutation, and BRAF mutation as predictive or prognostic markers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2011</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">December 2016</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>Objective response rate</measure>
    <time_frame>1.5 years</time_frame>
    <description>Objective response rate will be measured from the rate of complete response (disappearance of disease) and partial response (decrease at least 30% in the sum of the longest diameters of target lesions) by RECIST (response evaluation criteria in solid tumors) guidelines.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>1.5 years</time_frame>
    <description>Progression free survival time will be measured from the start of study treatment until documented tumor progression, or death due to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>1.5 years</time_frame>
    <description>Overall survival time will be measured from the start of study treatment until death due to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate</measure>
    <time_frame>1.5 years</time_frame>
    <description>Disease control rate will be measured from the rate of complete response (disappearance of disease), partial response (decrease at least 30% in the sum of the longest diameters of target lesions), and stable disease (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD) by RECIST (response evaluation criteria in solid tumors) guidelines.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicity profiles</measure>
    <time_frame>1.5 years</time_frame>
    <description>Adverse events will be descripted and graded using NCI-CTCAE version 4.0</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">37</enrollment>
  <condition>Pancreas Neoplasms</condition>
  <arm_group>
    <arm_group_label>GES (Gemcitabine, Erlotinib, S-1)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment will be delivered as a 3-week cycle.&#xD;
Gemcitabine 1000 mg/m² IV on day 1, 8&#xD;
Erlotinib 100 mg/day PO on day 1&#xD;
S-1 60 mg/m²/day PO on day 1-14</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GES (Gemcitabine, Erlotinib, S-1)</intervention_name>
    <description>Treatment will be delivered as a 3-week cycle.&#xD;
Gemcitabine 1000 mg/m² IV on day 1, 8&#xD;
Erlotinib 100 mg/day PO on day 1&#xD;
S-1 60 mg/m²/day PO on day 1-14</description>
    <arm_group_label>GES (Gemcitabine, Erlotinib, S-1)</arm_group_label>
    <other_name>Gemzar</other_name>
    <other_name>Tarceva</other_name>
    <other_name>TS-1</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pathologically confirmed locally advanced unresectable, recurrent or metastatic&#xD;
             adenocarcinoma of pancreas (Stage III-IV ; TNM staging system)&#xD;
&#xD;
          -  Measurable or evaluable disease by RECIST criteria 1.1&#xD;
&#xD;
          -  Minimum age of 18 years&#xD;
&#xD;
          -  ECOG Performance status 0-1&#xD;
&#xD;
          -  Prior adjuvant chemotherapy without gemcitabine, erlotinib or S-1 is allowed if more&#xD;
             than 4 weeks elapsed since completion of chemotherapy.&#xD;
&#xD;
          -  More than 4 weeks since completion of prior radiotherapy (measurable or evaluable&#xD;
             lesions should be outside the radiation field)&#xD;
&#xD;
          -  Adequate organ functions&#xD;
&#xD;
          -  Patients must sign an informed consent indicating that they are aware of the&#xD;
             investigational nature of the study in keeping with the policy of the hospital.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients treated previously with gemcitabine, erlotinib, or S-1 as adjuvant&#xD;
             chemotherapy.&#xD;
&#xD;
          -  Patients with CNS metastases&#xD;
&#xD;
          -  Patients with active infection, severe heart disease, uncontrollable hypertension or&#xD;
             diabetes mellitus, myocardial infarction during the preceding 6 months, pregnancy, or&#xD;
             breast feeding&#xD;
&#xD;
          -  Any previous or concurrent malignancy other than non-melanoma skin cancer or in situ&#xD;
             cancer of uterine cervix&#xD;
&#xD;
          -  Known history of cerebral or leptomeningeal metastases or neurologic disease&#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>Dae Young Zang, DM, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hallym University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hallym University Medical Center</name>
      <address>
        <city>Anyang</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>September 20, 2012</study_first_submitted>
  <study_first_submitted_qc>September 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 26, 2012</study_first_posted>
  <last_update_submitted>August 22, 2017</last_update_submitted>
  <last_update_submitted_qc>August 22, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 23, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>pancreas neoplasm</keyword>
  <keyword>gemcitabine</keyword>
  <keyword>erlotinib</keyword>
  <keyword>S-1</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pancreatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gemcitabine</mesh_term>
    <mesh_term>Erlotinib Hydrochloride</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT01693419
org study id: HMC-HO-GI-1201
nct id: NCT01693419
lead sponsor: 
collaborator: 
has dmc: No
This study will conduct a phase II study of gemcitabine, erlotinib, and S-1 as first-line
      chemotherapy in patients with advanced pancreatic cancer and evaluate the EGFR expression,
      KRAS mutation, and BRAF mutation as predictive or prognostic markers
Pancreatic ductal adenocarcinoma, also known as pancreatic cancer, is an eighth cause of
      cancer-related deaths in the world. The estimated worldwide incidence of pancreatic cancer
      was 277,000 cases and an estimated 266,000 patients died from the disease in 20081.

      Pancreatic cancer is more common in elderly persons than in younger persons, and
      characterised by early locoregional spread and distant metastasis. As a result, less than 20%
      of patients are diagnosed with localized, potentially curable disease, and the median
      survival is no longer than 3-4 months without effective treatment2.

      Single-agent chemotherapy with gemcitabine was considered as standard of care for patients
      with advanced pancreatic cancer, since Burris et al. demonstrated superiority of gemcitabine
      over 5-fluorouracil (5-FU) in respect of a survival benefit as well as an improvement in
      disease related symptoms in a randomized study3.

      Nevertheless, the activity of gemcitabine monotherapy in pancreatic cancer was modest, and
      there was a clear need to improve its efficacy by combining it with other anticancer drugs.

      Multiple agents such as 5-FU4, capecitabine5,6, cisplatin7,8, oxaliplatin9, pemetrexed10,
      irinotecan11, cetuximab12, and bevacizumab13, in combination with gemcitabine have been
      tested in clinical trials, however, they have failed to improve the outcome.

      The only agent that, in combination with gemcitabine, has shown a small, but statistically
      significant improvement, with a hazard ratio (HR) of 0.82, the absolute improvement in median
      overall survival (OS) of 5.9 months with gemcitabine versus 6.2 months with the combination,
      is erlotinib, a small-molecule inhibitor of the epidermal growth factor receptor (EGFR)14.
      Considering the modest improvement in survival by adding erlotinib to gemcitabine, new
      combination therapy that have a great impact is urgently needed.

      S-1 is an oral fluoropyrimidine derivative that combines tegafur (FT) with two modulators;
      5-chloro-2, 4-dihydroxypyridine (CDHP) and oteracil potassium (Oxo) in a 1:0.4:1 molar
      concentration ratio. The phase II trials of a combination of gemcitabine and S-1 have
      demonstrated objective response rates of 32-48% and median survival of 8-12 months 15-17.

      Therefore, we will conduct a phase II study of gemcitabine, erlotinib, and S-1 as first-line
      chemotherapy in patients with advanced pancreatic cancer and evaluate the EGFR expression,
      KRAS mutation, and BRAF mutation as predictive or prognostic markers.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective response rate
time frame: 1.5 years
description: Objective response rate will be measured from the rate of complete response (disappearance of disease) and partial response (decrease at least 30% in the sum of the longest diameters of target lesions) by RECIST (response evaluation criteria in solid tumors) guidelines.
measure: Progression free survival
time frame: 1.5 years
description: Progression free survival time will be measured from the start of study treatment until documented tumor progression, or death due to any cause
measure: Overall survival
time frame: 1.5 years
description: Overall survival time will be measured from the start of study treatment until death due to any cause
measure: Disease control rate
time frame: 1.5 years
description: Disease control rate will be measured from the rate of complete response (disappearance of disease), partial response (decrease at least 30% in the sum of the longest diameters of target lesions), and stable disease (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD) by RECIST (response evaluation criteria in solid tumors) guidelines.
measure: Toxicity profiles
time frame: 1.5 years
description: Adverse events will be descripted and graded using NCI-CTCAE version 4.0
arm group label: GES (Gemcitabine, Erlotinib, S-1)
arm group type: Experimental
description: Treatment will be delivered as a 3-week cycle.
Gemcitabine 1000 mg/m² IV on day 1, 8
Erlotinib 100 mg/day PO on day 1
S-1 60 mg/m²/day PO on day 1-14
intervention type: Drug
intervention name: GES (Gemcitabine, Erlotinib, S-1)
description: Treatment will be delivered as a 3-week cycle.
Gemcitabine 1000 mg/m² IV on day 1, 8
Erlotinib 100 mg/day PO on day 1
S-1 60 mg/m²/day PO on day 1-14
arm group label: GES (Gemcitabine, Erlotinib, S-1)
other name: Gemzar
other name: Tarceva
other name: TS-1
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dae Young Zang, DM, PhD
role: Principal Investigator
affiliation: Hallym University Medical Center
facility: 
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Pancreatic Neoplasms
mesh term: Gemcitabine
mesh term: Erlotinib Hydrochloride
sharing ipd: Undecided