<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/NCT02256800</url>
  </required_header>
  <id_info>
    <org_study_id>KMUHIRB-20130020</org_study_id>
    <nct_id>NCT02256800</nct_id>
  </id_info>
  <brief_title>Escalated Dose of Irinotecan in mCRC</brief_title>
  <official_title>Determination of the UGT1A1 Polymorphism as Guidance for Irinotecan Dose Escalation in Metastatic Colorectal Cancer Treated With First-Line Bevacizumab and FOLFIRI (PURE FIST)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jaw-Yuan Wang, MD, PhD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kaohsiung Medical University Chung-Ho Memorial Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Metastatic diseases were found in 20-25% of patients with initial diagnosis of colorectal&#xD;
      cancer and developed in up to 50% of patients. Owing to limited post-treatment response of&#xD;
      5-fluorouracil (5-FU) combined with leucovorin (LV) obtained in mCRC (metastatic colorectal&#xD;
      cancer) patients, other therapeutic agents with different mechanisms were considered, such as&#xD;
      irinotecan, a potent inhibitor of topoisomerase I, which is involved in the unwinding of DNA&#xD;
      during replication. Bevacizumab is a humanized monoclonal antibody that inhibits tumor&#xD;
      angiogenesis by blocking vascular endothelial growth factor (VEGF) and was the first&#xD;
      antiangiogenic agent approved for the treatment of cancer.&#xD;
&#xD;
      Infusional fluorouracil/leucovorin plus irinotecan-based regimen (FOLFIRI) with bevacizumab&#xD;
      has been widely used as first-line treatment for patients with metastatic colorectal cancer&#xD;
      (mCRC). Recently, the investigators have shown that prospective analysis of uridine&#xD;
      diphosphate glucuronosyl transferase 1A1 (UGT1A1) genotyping for irinotecan dose escalation&#xD;
      (FOLFIRI regimen) with combination of bevacizumab biweekly as the first-line setting in mCRC&#xD;
      patients (ASCO Abstract #491 - 2013 Gastrointestinal Cancers Symposium).&#xD;
&#xD;
      In this study, the investigators will enroll approximately 320 mCRC patients (It was&#xD;
      considered that an increase of response rate of 15% compared to conventional irinotecan dose&#xD;
      of 180 mg/m2, and these were chosen as parameters with which to calculate the study power.&#xD;
      Initial power calculation was suggested that a minimum of 140 patients in each group would be&#xD;
      required to achieve statistical significance with a power of 80% at the 5% significance&#xD;
      level. It is estimated that about 10% of 320 mCRC patients fail to complete the study). For&#xD;
      these enrolled patients, the investigators will randomize and divide these patients into two&#xD;
      groups: control group and study group. Control group includes mCRC patients who will receive&#xD;
      the conventional regimen of FOLFIRI plus bevacizumab. Otherwise, patients in the study group&#xD;
      will have genotyping of UGT1A1 before therapy, and dose escalating of irinotecan will depend&#xD;
      on results of genotyping.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Control group:&#xD;
&#xD;
      Regimen for treatment consisted of bevacizumab (Avastin) 5mg/Kg (IV infusion) on day 1,&#xD;
      follow by irinotecan (180 mg/m2 as a 120-min IV infusion), LV (400 mg/m2 IV infusion over 2&#xD;
      hours), and 5-FU (2800 mg/m2 IV infusion over a 46-hour period), repeated every 2 weeks.&#xD;
&#xD;
      Study group: FOLFIRI (infusional fluorouracil/leucovorin plus irinotecan) + Bevacizumab. The&#xD;
      dosage of irinotecan is adjusted to the UGT1A1 genotyping&#xD;
&#xD;
      The wild-type (6/6) of UGT1A1:&#xD;
&#xD;
      Regimen for treatment consisted of bevacizumab (Avastin) 5mg/Kg (IV infusion) on day 1,&#xD;
      follow by irinotecan (180 mg/m2 as a 120-min IV infusion), LV (400 mg/m2 IV infusion over 2&#xD;
      hours), and 5-FU (2800 mg/m2 IV infusion over a 46-hour period), repeated every 2 weeks.&#xD;
&#xD;
      After 2 cycles of each different dose of irinotecan, we will observe the adverse effects&#xD;
      (AEs) of hematological / non-hematological. If the grade is under the grade 2, we will&#xD;
      escalate the dose of 30 mg/m2 gradually. The estimated maximal dose of irinotecan is 260&#xD;
      mg/m2.&#xD;
&#xD;
      The (6,7) type of UGT1A1:&#xD;
&#xD;
      Regimen for treatment consisted of bevacizumab (Avastin) 5mg/Kg (IV infusion) on day 1,&#xD;
      follow by irinotecan (180 mg/m2 as a 120-min IV infusion), LV (400 mg/m2 IV infusion over 2&#xD;
      hours), and 5-FU (2800 mg/m2 IV infusion over a 46-hour period), repeated every 2 weeks.&#xD;
&#xD;
      After 2 cycles of each different dose of irinotecan, we will observe the adverse effects&#xD;
      (AEs) of hematological / non-hematological. If the grade is under the grade 2, we will&#xD;
      escalate the dose of 30 mg/m2 gradually. The estimated maximal dose of irinotecan is 240&#xD;
      mg/m2.&#xD;
&#xD;
      The (7,7) type of UGT1A1:&#xD;
&#xD;
      Regimen for treatment consisted of bevacizumab (Avastin) 5mg/Kg (IV infusion) on day 1,&#xD;
      follow by irinotecan (120 mg/m2 as a 120-min IV infusion), LV (400 mg/m2 IV infusion over 2&#xD;
      hours), and 5-FU (2800 mg/m2 IV infusion over a 46-hour period), repeated every 2 weeks.&#xD;
&#xD;
      After 2 cycles of each different dose of irinotecan, we will observe the adverse effects&#xD;
      (AEs) of hematological / non-hematological. If the grade is under the grade 2, we will&#xD;
      escalate the dose of 30 mg/m2 gradually. The estimated maximal dose of irinotecan is 180&#xD;
      mg/m2.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 13, 2014</start_date>
  <completion_date type="Actual">November 30, 2017</completion_date>
  <primary_completion_date type="Actual">November 30, 2017</primary_completion_date>
  <phase>N/A</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>three to six months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective response rates</measure>
    <time_frame>three to six months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>overall survival</measure>
    <time_frame>three to six months</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">213</enrollment>
  <condition>Metastatic Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>UGT1A1 genotyping (6,6)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The investigators will escalate the dosage of irinotecan from 180mg/m2 to 260 mg/m2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>UGTA1T1 genotyping (6,7)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The investigators will escalate the dosage of irinotecan from 180mg/m2 to 240 mg/m2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>UGTA1T1 genotyping (7,7)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The investigators will escalate the dosage of irinotecan from 120mg/m2 to 180 mg/m2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>UGT1A1 non-genotyping</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The investigators will maintain the dosage of irinotecan by 180mg/m2</description>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>UGT1A1 genotyping (6,6)</intervention_name>
    <description>The investigators will use the regimen as following:&#xD;
Regimen for treatment consisted of bevacizumab (Avastin) 5mg/Kg (IV infusion) on day 1, follow by irinotecan (180 mg/m2 as a 120-min IV infusion), Leucovorin (400 mg/m2 IV infusion over 2 hours), and 5-FU (2800 mg/m2 IV infusion over a 46-hour period), repeated every 2 weeks.&#xD;
After 2 cycles of each different dose of irinotecan, we will observe the adverse effects (AEs) of hematological / non-hematological. If the grade is under the grade 2, we will escalate the dose of 30 mg/m2 gradually. The estimated maximal dose of irinotecan is 260 mg/m2.</description>
    <arm_group_label>UGT1A1 genotyping (6,6)</arm_group_label>
    <other_name>UGT1A1*1*1</other_name>
  </intervention>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>UGTIA1 genotyping (6,7)</intervention_name>
    <description>The investigators will use the regimen as following:&#xD;
Regimen for treatment consisted of bevacizumab (Avastin) 5mg/Kg (IV infusion) on day 1, follow by irinotecan (180 mg/m2 as a 120-min IV infusion), Leucovorin (400 mg/m2 IV infusion over 2 hours), and 5-FU (2800 mg/m2 IV infusion over a 46-hour period), repeated every 2 weeks.&#xD;
After 2 cycles of each different dose of irinotecan, we will observe the adverse effects (AEs) of hematological / non-hematological. If the grade is under the grade 2, we will escalate the dose of 30 mg/m2 gradually. The estimated maximal dose of irinotecan is 240 mg/m2.</description>
    <arm_group_label>UGTA1T1 genotyping (6,7)</arm_group_label>
    <other_name>UGT1A1*1*28</other_name>
  </intervention>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>UGTIA1 genotyping (7,7)</intervention_name>
    <description>The investigators will use the regimen as following:&#xD;
Regimen for treatment consisted of bevacizumab (Avastin) 5mg/Kg (IV infusion) on day 1, follow by irinotecan (120 mg/m2 as a 120-min IV infusion), Leucovorin (400 mg/m2 IV infusion over 2 hours), and 5-FU (2800 mg/m2 IV infusion over a 46-hour period), repeated every 2 weeks.&#xD;
After 2 cycles of each different dose of irinotecan, we will observe the adverse effects (AEs) of hematological / non-hematological. If the grade is under the grade 2, we will escalate the dose of 30 mg/m2 gradually. The estimated maximal dose of irinotecan is 180 mg/m2.</description>
    <arm_group_label>UGTA1T1 genotyping (7,7)</arm_group_label>
    <other_name>UGT1A1*28*28</other_name>
  </intervention>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>UGT1A1 non-genotyping</intervention_name>
    <description>The investigators will use the regimen as following:&#xD;
Regimen for treatment consisted of bevacizumab (Avastin) 5mg/Kg (IV infusion) on day 1, follow by irinotecan (180 mg/m2 as a 120-min IV infusion), Leucovorin (400 mg/m2 IV infusion over 2 hours), and 5-FU (2800 mg/m2 IV infusion over a 46-hour period), repeated every 2 weeks.</description>
    <arm_group_label>UGT1A1 non-genotyping</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>bevacizumab (Avastin)</intervention_name>
    <description>bevacizumab as target therapy</description>
    <arm_group_label>UGT1A1 genotyping (6,6)</arm_group_label>
    <arm_group_label>UGT1A1 non-genotyping</arm_group_label>
    <arm_group_label>UGTA1T1 genotyping (6,7)</arm_group_label>
    <arm_group_label>UGTA1T1 genotyping (7,7)</arm_group_label>
    <other_name>Avastin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>irinotecan</intervention_name>
    <description>irinotecan as escalating dose according to UGT1A1 genotyping</description>
    <arm_group_label>UGT1A1 genotyping (6,6)</arm_group_label>
    <arm_group_label>UGT1A1 non-genotyping</arm_group_label>
    <arm_group_label>UGTA1T1 genotyping (6,7)</arm_group_label>
    <arm_group_label>UGTA1T1 genotyping (7,7)</arm_group_label>
    <other_name>Campto</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Leucovorin</intervention_name>
    <description>combined with 5-FU</description>
    <arm_group_label>UGT1A1 genotyping (6,6)</arm_group_label>
    <arm_group_label>UGT1A1 non-genotyping</arm_group_label>
    <arm_group_label>UGTA1T1 genotyping (6,7)</arm_group_label>
    <arm_group_label>UGTA1T1 genotyping (7,7)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5-FU</intervention_name>
    <description>combined with irinotecan</description>
    <arm_group_label>UGT1A1 genotyping (6,6)</arm_group_label>
    <arm_group_label>UGT1A1 non-genotyping</arm_group_label>
    <arm_group_label>UGTA1T1 genotyping (6,7)</arm_group_label>
    <arm_group_label>UGTA1T1 genotyping (7,7)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. 20 y/o ≦ Age ≦ 80y/o&#xD;
&#xD;
          2. Either metachronous or synchronous mCRC can be enrolled&#xD;
&#xD;
          3. Female patients need not ready to be pregnant or breastfeeding&#xD;
&#xD;
          4. No major underlying diseases (such as cardiovascular, cerebrovascular, malignant&#xD;
             hypertension, kidney, liver and other major diseases)&#xD;
&#xD;
          5. mCRC be proven by pathologists or radiologists&#xD;
&#xD;
          6. Subjects are willing to sign an inform consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who do not meet the including criteria or unwilling to participate&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Chung-Ho Memorial Hospital, Kaohsiung Medical University:</name>
      <address>
        <city>Kaohsiung</city>
        <zip>807</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>September 18, 2014</study_first_submitted>
  <study_first_submitted_qc>October 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 6, 2014</study_first_posted>
  <last_update_submitted>November 9, 2021</last_update_submitted>
  <last_update_submitted_qc>November 9, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 17, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Kaohsiung Medical University Chung-Ho Memorial Hospital</investigator_affiliation>
    <investigator_full_name>Jaw-Yuan Wang, MD, PhD</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leucovorin</mesh_term>
    <mesh_term>Bevacizumab</mesh_term>
    <mesh_term>Irinotecan</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/NCT02256800
org study id: KMUHIRB-20130020
nct id: NCT02256800
lead sponsor: 
has dmc: No
Metastatic diseases were found in 20-25% of patients with initial diagnosis of colorectal
      cancer and developed in up to 50% of patients. Owing to limited post-treatment response of
      5-fluorouracil (5-FU) combined with leucovorin (LV) obtained in mCRC (metastatic colorectal
      cancer) patients, other therapeutic agents with different mechanisms were considered, such as
      irinotecan, a potent inhibitor of topoisomerase I, which is involved in the unwinding of DNA
      during replication. Bevacizumab is a humanized monoclonal antibody that inhibits tumor
      angiogenesis by blocking vascular endothelial growth factor (VEGF) and was the first
      antiangiogenic agent approved for the treatment of cancer.

      Infusional fluorouracil/leucovorin plus irinotecan-based regimen (FOLFIRI) with bevacizumab
      has been widely used as first-line treatment for patients with metastatic colorectal cancer
      (mCRC). Recently, the investigators have shown that prospective analysis of uridine
      diphosphate glucuronosyl transferase 1A1 (UGT1A1) genotyping for irinotecan dose escalation
      (FOLFIRI regimen) with combination of bevacizumab biweekly as the first-line setting in mCRC
      patients (ASCO Abstract #491 - 2013 Gastrointestinal Cancers Symposium).

      In this study, the investigators will enroll approximately 320 mCRC patients (It was
      considered that an increase of response rate of 15% compared to conventional irinotecan dose
      of 180 mg/m2, and these were chosen as parameters with which to calculate the study power.
      Initial power calculation was suggested that a minimum of 140 patients in each group would be
      required to achieve statistical significance with a power of 80% at the 5% significance
      level. It is estimated that about 10% of 320 mCRC patients fail to complete the study). For
      these enrolled patients, the investigators will randomize and divide these patients into two
      groups: control group and study group. Control group includes mCRC patients who will receive
      the conventional regimen of FOLFIRI plus bevacizumab. Otherwise, patients in the study group
      will have genotyping of UGT1A1 before therapy, and dose escalating of irinotecan will depend
      on results of genotyping.
Control group:

      Regimen for treatment consisted of bevacizumab (Avastin) 5mg/Kg (IV infusion) on day 1,
      follow by irinotecan (180 mg/m2 as a 120-min IV infusion), LV (400 mg/m2 IV infusion over 2
      hours), and 5-FU (2800 mg/m2 IV infusion over a 46-hour period), repeated every 2 weeks.

      Study group: FOLFIRI (infusional fluorouracil/leucovorin plus irinotecan) + Bevacizumab. The
      dosage of irinotecan is adjusted to the UGT1A1 genotyping

      The wild-type (6/6) of UGT1A1:

      Regimen for treatment consisted of bevacizumab (Avastin) 5mg/Kg (IV infusion) on day 1,
      follow by irinotecan (180 mg/m2 as a 120-min IV infusion), LV (400 mg/m2 IV infusion over 2
      hours), and 5-FU (2800 mg/m2 IV infusion over a 46-hour period), repeated every 2 weeks.

      After 2 cycles of each different dose of irinotecan, we will observe the adverse effects
      (AEs) of hematological / non-hematological. If the grade is under the grade 2, we will
      escalate the dose of 30 mg/m2 gradually. The estimated maximal dose of irinotecan is 260
      mg/m2.

      The (6,7) type of UGT1A1:

      Regimen for treatment consisted of bevacizumab (Avastin) 5mg/Kg (IV infusion) on day 1,
      follow by irinotecan (180 mg/m2 as a 120-min IV infusion), LV (400 mg/m2 IV infusion over 2
      hours), and 5-FU (2800 mg/m2 IV infusion over a 46-hour period), repeated every 2 weeks.

      After 2 cycles of each different dose of irinotecan, we will observe the adverse effects
      (AEs) of hematological / non-hematological. If the grade is under the grade 2, we will
      escalate the dose of 30 mg/m2 gradually. The estimated maximal dose of irinotecan is 240
      mg/m2.

      The (7,7) type of UGT1A1:

      Regimen for treatment consisted of bevacizumab (Avastin) 5mg/Kg (IV infusion) on day 1,
      follow by irinotecan (120 mg/m2 as a 120-min IV infusion), LV (400 mg/m2 IV infusion over 2
      hours), and 5-FU (2800 mg/m2 IV infusion over a 46-hour period), repeated every 2 weeks.

      After 2 cycles of each different dose of irinotecan, we will observe the adverse effects
      (AEs) of hematological / non-hematological. If the grade is under the grade 2, we will
      escalate the dose of 30 mg/m2 gradually. The estimated maximal dose of irinotecan is 180
      mg/m2.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free survival
time frame: three to six months
measure: Objective response rates
time frame: three to six months
measure: overall survival
time frame: three to six months
arm group label: UGT1A1 genotyping (6,6)
arm group type: Experimental
description: The investigators will escalate the dosage of irinotecan from 180mg/m2 to 260 mg/m2
arm group label: UGTA1T1 genotyping (6,7)
arm group type: Experimental
description: The investigators will escalate the dosage of irinotecan from 180mg/m2 to 240 mg/m2
arm group label: UGTA1T1 genotyping (7,7)
arm group type: Experimental
description: The investigators will escalate the dosage of irinotecan from 120mg/m2 to 180 mg/m2
arm group label: UGT1A1 non-genotyping
arm group type: Experimental
description: The investigators will maintain the dosage of irinotecan by 180mg/m2
intervention type: Genetic
intervention name: UGT1A1 genotyping (6,6)
description: The investigators will use the regimen as following:
Regimen for treatment consisted of bevacizumab (Avastin) 5mg/Kg (IV infusion) on day 1, follow by irinotecan (180 mg/m2 as a 120-min IV infusion), Leucovorin (400 mg/m2 IV infusion over 2 hours), and 5-FU (2800 mg/m2 IV infusion over a 46-hour period), repeated every 2 weeks.
After 2 cycles of each different dose of irinotecan, we will observe the adverse effects (AEs) of hematological / non-hematological. If the grade is under the grade 2, we will escalate the dose of 30 mg/m2 gradually. The estimated maximal dose of irinotecan is 260 mg/m2.
arm group label: UGT1A1 genotyping (6,6)
other name: UGT1A1*1*1
intervention type: Genetic
intervention name: UGTIA1 genotyping (6,7)
description: The investigators will use the regimen as following:
Regimen for treatment consisted of bevacizumab (Avastin) 5mg/Kg (IV infusion) on day 1, follow by irinotecan (180 mg/m2 as a 120-min IV infusion), Leucovorin (400 mg/m2 IV infusion over 2 hours), and 5-FU (2800 mg/m2 IV infusion over a 46-hour period), repeated every 2 weeks.
After 2 cycles of each different dose of irinotecan, we will observe the adverse effects (AEs) of hematological / non-hematological. If the grade is under the grade 2, we will escalate the dose of 30 mg/m2 gradually. The estimated maximal dose of irinotecan is 240 mg/m2.
arm group label: UGTA1T1 genotyping (6,7)
other name: UGT1A1*1*28
intervention type: Genetic
intervention name: UGTIA1 genotyping (7,7)
description: The investigators will use the regimen as following:
Regimen for treatment consisted of bevacizumab (Avastin) 5mg/Kg (IV infusion) on day 1, follow by irinotecan (120 mg/m2 as a 120-min IV infusion), Leucovorin (400 mg/m2 IV infusion over 2 hours), and 5-FU (2800 mg/m2 IV infusion over a 46-hour period), repeated every 2 weeks.
After 2 cycles of each different dose of irinotecan, we will observe the adverse effects (AEs) of hematological / non-hematological. If the grade is under the grade 2, we will escalate the dose of 30 mg/m2 gradually. The estimated maximal dose of irinotecan is 180 mg/m2.
arm group label: UGTA1T1 genotyping (7,7)
other name: UGT1A1*28*28
intervention type: Genetic
intervention name: UGT1A1 non-genotyping
description: The investigators will use the regimen as following:
Regimen for treatment consisted of bevacizumab (Avastin) 5mg/Kg (IV infusion) on day 1, follow by irinotecan (180 mg/m2 as a 120-min IV infusion), Leucovorin (400 mg/m2 IV infusion over 2 hours), and 5-FU (2800 mg/m2 IV infusion over a 46-hour period), repeated every 2 weeks.
arm group label: UGT1A1 non-genotyping
intervention type: Drug
intervention name: bevacizumab (Avastin)
description: bevacizumab as target therapy
arm group label: UGT1A1 genotyping (6,6)
arm group label: UGT1A1 non-genotyping
arm group label: UGTA1T1 genotyping (6,7)
arm group label: UGTA1T1 genotyping (7,7)
other name: Avastin
intervention type: Drug
intervention name: irinotecan
description: irinotecan as escalating dose according to UGT1A1 genotyping
arm group label: UGT1A1 genotyping (6,6)
arm group label: UGT1A1 non-genotyping
arm group label: UGTA1T1 genotyping (6,7)
arm group label: UGTA1T1 genotyping (7,7)
other name: Campto
intervention type: Drug
intervention name: Leucovorin
description: combined with 5-FU
arm group label: UGT1A1 genotyping (6,6)
arm group label: UGT1A1 non-genotyping
arm group label: UGTA1T1 genotyping (6,7)
arm group label: UGTA1T1 genotyping (7,7)
intervention type: Drug
intervention name: 5-FU
description: combined with irinotecan
arm group label: UGT1A1 genotyping (6,6)
arm group label: UGT1A1 non-genotyping
arm group label: UGTA1T1 genotyping (6,7)
arm group label: UGTA1T1 genotyping (7,7)
criteria: 
gender: All
minimum age: 20 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
country: Taiwan
responsible party type: Sponsor-Investigator
investigator affiliation: Kaohsiung Medical University Chung-Ho Memorial Hospital
investigator full name: Jaw-Yuan Wang, MD, PhD
investigator title: Professor
mesh term: Colorectal Neoplasms
mesh term: Leucovorin
mesh term: Bevacizumab
mesh term: Irinotecan