<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/NCT04401709</url>
  </required_header>
  <id_info>
    <org_study_id>2020-01-101</org_study_id>
    <nct_id>NCT04401709</nct_id>
  </id_info>
  <brief_title>Gemcitabine+ Capecitabine Vs Capecitabine in Curatively Resected Biliary Tract Cancer</brief_title>
  <official_title>A Randomized, Multi-center Phase III Trial of Adjuvant Chemotherapy With Gemcitabine and Capecitabine Compared to Capecitabine Alone in Curatively Resected Biliary Tract Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Samsung Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Samsung Medical Center</source>
  <oversight_info>
    <has_dmc>No</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>
      This clinical trial is an open-label, multicenter, phase 3 clinical trial to study the&#xD;
      efficacy and safety of adjuvant gemcitabine + capecitabine combination treatment in patients&#xD;
      with resectable biliary tract cancer according to imaging studies after surgery. All the&#xD;
      patients must complete a consent forms before participating in the clinical trial, and the&#xD;
      estimated enrollment period is 36 months after IRB approval.&#xD;
&#xD;
      Drug Dose and Schedule:&#xD;
&#xD;
        -  Cohort 1: Gemcitabine/Capecitabine, every 4 weeks, total 6 cycles gemcitabine1,000 mg/m2&#xD;
           over 30 min D1, D8, D15 capecitabine 1660 mg/m2, D1-21&#xD;
&#xD;
        -  Cohort 2: Capecitabine, everu 3 weeks, total 8 cycles capecitabine 2,500 mg/m2 D1-14&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. Study Background &amp; Rationale:adjuvant capecitabine monotherapy following surgery is&#xD;
           regarded as standard treatment after phase 3 BILCAP trial, we need further phase 3&#xD;
           clinical trials to evaluate efficacy of doublet combination adjuvant chemotherapy for&#xD;
           Biliary Track Cancer after surgery. Since Korea has much higher incidence rate of&#xD;
           Biliary Track Cancer compared to western countries, Korea is considered to be a region&#xD;
           that can lead large-scale Biliary Track Cancer clinical trials. In this background, we&#xD;
           intend to conduct a randomized phase 3 study to compare adjuvant gemcitabine+cisplatin&#xD;
           combination therapy with camecitabine monotherapy following curative intent surgical&#xD;
           resection in patients with Biliary Track Cancer .&#xD;
&#xD;
        2. Primary Objective:&#xD;
&#xD;
             -  Disease-free survival at 24 months (2-year DFS)&#xD;
&#xD;
        3. Primary Hypothesis:&#xD;
&#xD;
           Adjuvant gemcitabine and capecitabine combination treatment confers diseae free survival&#xD;
           benefit over capecitabine monotherapy after curative intent surgical resection of&#xD;
           biliary tract cancer&#xD;
&#xD;
        4. Study Design:&#xD;
&#xD;
      This clinical trial is an open-label, multicenter, phase 3 clinical trial to study the&#xD;
      efficacy and safety of adjuvant gemcitabine + capecitabine combination treatment in patients&#xD;
      with resectable biliary tract cancer according to imaging studies after surgery. All the&#xD;
      patients must complete a consent forms before participating in the clinical trial, and the&#xD;
      estimated enrollment period is 36 months after IRB approval.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 1, 2021</start_date>
  <completion_date type="Anticipated">March 30, 2025</completion_date>
  <primary_completion_date type="Anticipated">March 30, 2025</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Two-year disease free survival (DFS)</measure>
    <time_frame>24 months later</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>24 months later</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">490</enrollment>
  <condition>Biliary Tract Cancer</condition>
  <arm_group>
    <arm_group_label>Gemcitabine/Capecitabine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>gemcitabine1,000 mg/m2 over 30 min D1, D8, D15 capecitabine 1660 mg/m2, D1-21</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Capecitabine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>capecitabine 2,500 mg/m2 D1-14</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine/Capecitabine</intervention_name>
    <description>gemcitabine 1,000 mg / m2 IV on day 1, 8, and 15 of each cycle Capecitabine 1,660mg / m2 PO twice daily 1 ~ 21 days for 4 weeks</description>
    <arm_group_label>Gemcitabine/Capecitabine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine</intervention_name>
    <description>total 8 cycles Capecitabine 1,250 mg / m2 PO twice daily 1 ~ 14 days for 3 weeks</description>
    <arm_group_label>Capecitabine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with histologically confirmed adenocarcinoma of biliary tract canacer&#xD;
             (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder&#xD;
             cancer) after curative intent R0 or R1 surgical resection&#xD;
&#xD;
          2. Pathologic disease stage of T2-4, N0-2, M0 after surgery, according to AJCC 8th TNM&#xD;
             staging&#xD;
&#xD;
          3. Patients who complete resection (R0 or R1 resection) for biliary tract cancer within&#xD;
             12 weeks of the adjuvant chemotherapy&#xD;
&#xD;
          4. No distant metastasis&#xD;
&#xD;
          5. ECOG performance sstatus score of 0 or 1&#xD;
&#xD;
          6. Age 19 years or older&#xD;
&#xD;
          7. Adequate bone marrow fuction (neutrophils ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L and&#xD;
             hemoglobin ≥9 g/dL)&#xD;
&#xD;
          8. Adequate liver function (total bilirubin &lt; 1.5 fold the upper limit of normal of the&#xD;
             study site (ULN), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) &lt;&#xD;
             5.0 x ULN)&#xD;
&#xD;
          9. Adequate kidney function (Creatinine &lt; 1.5 x ULN)&#xD;
&#xD;
         10. Unresolved systemic active infection (except for chronic viral hepatitis taking&#xD;
             antiviral drugs)&#xD;
&#xD;
         11. Not receiving other drugs for clinical trials or chemotherapy within 30 days prior to&#xD;
             randomization&#xD;
&#xD;
         12. A female participant who is not post-menopausal or amenorrhea less than 12 consecutive&#xD;
             months without specific reasons is eligible to participate if she is not pregnant,&#xD;
             confirmed by serum tests within 7 days before the initiation of chemotherapy&#xD;
&#xD;
         13. The participants provide written informed consent for the study.&#xD;
&#xD;
         14. No prior chemotherapy for biliary tract cancer&#xD;
&#xD;
         15. Participants of childbearing potential must agree to use an adequate method of&#xD;
             contraception for the course of the study throught 120 days after the last dose of&#xD;
             chemotherapy (oral contraceptives or mechanical contraception such as intrauterine&#xD;
             devices or contraceptive barriers and etc). Childbearing potential female is who is&#xD;
             not post-menopausal or amenorrhea less than 12 consecutive months without specific&#xD;
             reasons&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Other histology type than adenocarcinoma (such as HCC-CCC mixed type or neuroendocrine&#xD;
             tumor)&#xD;
&#xD;
          2. Ampula of vater cancer&#xD;
&#xD;
          3. Has known additional malignancy (participants with non-melanoma skin cancer, or&#xD;
             carcinoma in situ (e.g. breast carcinoma, prostate cancer) that have undergone&#xD;
             potentially curative therapy without recurrence for more than 3 years are not&#xD;
             excluded)&#xD;
&#xD;
          4. Has a history or current evidence of any condition, therapy, or laboratory abnormality&#xD;
             that might confound the results of the study, interfere with the subject's&#xD;
             participation for the full duration of the study, or is not in the best interest of&#xD;
             the subject to participate, in the opinion of the treating investigator.&#xD;
&#xD;
          5. Has an active infection requiring systemic therapy (bacteria, virus, fungal, etc)&#xD;
&#xD;
          6. Has a known history of Human Immunodeficiency Virus (HIV)&#xD;
&#xD;
          7. Has an active of hepatitis A or B (patients under anti-B-viral treatment with HBV DNA&#xD;
             1000≤copies/ml is allowed to particiapte).&#xD;
&#xD;
          8. Has a history of severe hemorrhage (gastrointestinal or neurologic) within 2 weeks&#xD;
             prior randomization&#xD;
&#xD;
          9. Is unable to take oral drug due to gastrointestinal obstruction or any other&#xD;
             conditions.&#xD;
&#xD;
         10. Any history of significant cardiac disease within 3 months prior to randomization&#xD;
             including unstable angina, NYHA (The New York Heart Association )III or IV congestive&#xD;
             heart failure, myocardiac infarction, or severe uncontrolled arrhythmias&#xD;
&#xD;
         11. Pregnant, breast-feeding or pregnancy test positive female patients&#xD;
&#xD;
         12. Has any contraindications for investigational drug&#xD;
&#xD;
               -  History of hypersensitivity to capecitabine or gemcitabine&#xD;
&#xD;
               -  Any hypersensitivity to fluorouracil drugs&#xD;
&#xD;
               -  Concurrent administration with sorivudine or brivudine&#xD;
&#xD;
               -  DPD(dihydro-pyridine dehydrogenase) deficiency&#xD;
&#xD;
               -  History of TS-1(tegafur / gimeracil / oteracil) administration&#xD;
&#xD;
               -  Galactose intolerance, Lapp lactase deficince, glucose-galactose malabsorption&#xD;
&#xD;
               -  Interstitial pneumonia or pulmonary fibrosis&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>JoonOh Park, doctor</last_name>
    <phone>82-2-3410-3459</phone>
    <email>joonoh.park@samsung.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>135-710</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joon Oh Park, M.D., Ph.D</last_name>
      <phone>82 2 3410 3459</phone>
      <email>oncopark@skku.edu</email>
    </contact>
    <contact_backup>
      <last_name>yoon Jeong Ahn</last_name>
      <phone>221487395</phone>
      <phone_ext>82</phone_ext>
    </contact_backup>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>May 19, 2020</study_first_submitted>
  <study_first_submitted_qc>May 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 26, 2020</study_first_posted>
  <last_update_submitted>June 13, 2022</last_update_submitted>
  <last_update_submitted_qc>June 13, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 15, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Samsung Medical Center</investigator_affiliation>
    <investigator_full_name>Joon Oh Park</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Biliary Tract 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>Capecitabine</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/NCT04401709
org study id: 2020-01-101
nct id: NCT04401709
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This clinical trial is an open-label, multicenter, phase 3 clinical trial to study the
      efficacy and safety of adjuvant gemcitabine + capecitabine combination treatment in patients
      with resectable biliary tract cancer according to imaging studies after surgery. All the
      patients must complete a consent forms before participating in the clinical trial, and the
      estimated enrollment period is 36 months after IRB approval.

      Drug Dose and Schedule:

        -  Cohort 1: Gemcitabine/Capecitabine, every 4 weeks, total 6 cycles gemcitabine1,000 mg/m2
           over 30 min D1, D8, D15 capecitabine 1660 mg/m2, D1-21

        -  Cohort 2: Capecitabine, everu 3 weeks, total 8 cycles capecitabine 2,500 mg/m2 D1-14
1. Study Background & Rationale:adjuvant capecitabine monotherapy following surgery is
           regarded as standard treatment after phase 3 BILCAP trial, we need further phase 3
           clinical trials to evaluate efficacy of doublet combination adjuvant chemotherapy for
           Biliary Track Cancer after surgery. Since Korea has much higher incidence rate of
           Biliary Track Cancer compared to western countries, Korea is considered to be a region
           that can lead large-scale Biliary Track Cancer clinical trials. In this background, we
           intend to conduct a randomized phase 3 study to compare adjuvant gemcitabine+cisplatin
           combination therapy with camecitabine monotherapy following curative intent surgical
           resection in patients with Biliary Track Cancer .

        2. Primary Objective:

             -  Disease-free survival at 24 months (2-year DFS)

        3. Primary Hypothesis:

           Adjuvant gemcitabine and capecitabine combination treatment confers diseae free survival
           benefit over capecitabine monotherapy after curative intent surgical resection of
           biliary tract cancer

        4. Study Design:

      This clinical trial is an open-label, multicenter, phase 3 clinical trial to study the
      efficacy and safety of adjuvant gemcitabine + capecitabine combination treatment in patients
      with resectable biliary tract cancer according to imaging studies after surgery. All the
      patients must complete a consent forms before participating in the clinical trial, and the
      estimated enrollment period is 36 months after IRB approval.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Two-year disease free survival (DFS)
time frame: 24 months later
measure: Overall Survival (OS)
time frame: 24 months later
arm group label: Gemcitabine/Capecitabine
arm group type: Experimental
description: gemcitabine1,000 mg/m2 over 30 min D1, D8, D15 capecitabine 1660 mg/m2, D1-21
arm group label: Capecitabine
arm group type: Active Comparator
description: capecitabine 2,500 mg/m2 D1-14
intervention type: Drug
intervention name: Gemcitabine/Capecitabine
description: gemcitabine 1,000 mg / m2 IV on day 1, 8, and 15 of each cycle Capecitabine 1,660mg / m2 PO twice daily 1 ~ 21 days for 4 weeks
arm group label: Gemcitabine/Capecitabine
intervention type: Drug
intervention name: Capecitabine
description: total 8 cycles Capecitabine 1,250 mg / m2 PO twice daily 1 ~ 14 days for 3 weeks
arm group label: Capecitabine
criteria: 
gender: All
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
last name: JoonOh Park, doctor
phone: 82-2-3410-3459
email: joonoh.park@samsung.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: Korea, Republic of
responsible party type: Principal Investigator
investigator affiliation: Samsung Medical Center
investigator full name: Joon Oh Park
investigator title: Principal Investigator
mesh term: Biliary Tract Neoplasms
mesh term: Gemcitabine
mesh term: Capecitabine