<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/NCT03823079</url>
  </required_header>
  <id_info>
    <org_study_id>FDRT-009</org_study_id>
    <nct_id>NCT03823079</nct_id>
  </id_info>
  <brief_title>Comparison of Interleukin-11 and rhTPO for Recurrent Colorectal Cancer Patients With Thrombocytopenia</brief_title>
  <official_title>A Randomized Phase II Study of Recombinant Human Thrombopoietin (Rh-TPO) and Recombinant Human Interleukin-11 (rhIL-11) for Recurrent Colorectal Cancer (CRC) Patients With Thrombocytopenia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fudan University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fudan University</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 randomized controlled clinical phase II study was designed to compare the effect of&#xD;
      rhTPO with rhIL-11 in improving thrombocytopenia in patients with recurrent colorectal cancer&#xD;
      who underwent radiotherapy and with thrombocytopenia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Most patients with recurrent CRC have undergone a six-month postoperative adjuvant&#xD;
      chemotherapy with oxaliplatin plus fluorouracil. Although the main dose-limiting side effect&#xD;
      of oxaliplatin is neurotoxicity, with the widespread use of this drug, there are more and&#xD;
      more reports that oxaliplatin is discontinued because of thrombocytopenia, which increases&#xD;
      the risk of bleeding, rate of blood transfusion needs and length of stay. On the other hand,&#xD;
      patients undergoing pelvic radiotherapy may also experience significant bone marrow&#xD;
      suppression because flat bones such as the tibia may be exposed to high doses radiation. Low&#xD;
      platelet counts is an urgent problem to be solved in order to give adequate quantitative&#xD;
      radiotherapy. This randomized controlled clinical phase II study was designed to compare the&#xD;
      effect of rhTPO with rhIL-11 in improving thrombocytopenia in patients with recurrent&#xD;
      colorectal cancer who underwent radiotherapy and with thrombocytopenia, thus providing more&#xD;
      evidence in clinical practice.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">February 1, 2019</start_date>
  <completion_date type="Anticipated">February 1, 2020</completion_date>
  <primary_completion_date type="Anticipated">September 1, 2019</primary_completion_date>
  <phase>Phase 2</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>the rate of recovery of platelet accounts</measure>
    <time_frame>From date of chemoradiation until the date of first documented recovery, assessed up to 6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>the duration after returning to normal</measure>
    <time_frame>From date of first documented recovery until the date of first documented decrease of platelet accounts, assessed up to 6 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>cycles of concurrent chemotherapy patients received during radiotherapy</measure>
    <time_frame>through chemoradiation, an average of 5 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change of participant quality of life during treatment as assessed by EORTC-quality of life questionnaire-C30</measure>
    <time_frame>at the beginning and the end of chemoradiation.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change of participant quality of life during treatment as assessed by EuroQol-5 dimensional (EQ-5D) questionnaire</measure>
    <time_frame>at the beginning and the end of chemoradiation.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the rate of pathological complete response.</measure>
    <time_frame>Surgery scheduled 6-8 weeks after the end of chemoradiation</time_frame>
    <description>pathological complete response (pCR) was defined no viable cancer cell under the examination of surgical resection specimen.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Recurrent Colorectal Carcinoma</condition>
  <condition>Thrombopenia</condition>
  <arm_group>
    <arm_group_label>rhTPO arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>rhTPO: 300 u/kg, subcutaneous injection, per day. (stopped as soon as the platelet count rises to normal)&#xD;
Concurrent Chemoradiotherapy:&#xD;
Radiation: judged according to the tumor site and radiotherapy purpose.&#xD;
Irinotecan: 80 mg/m2 (UGT1A1*28 6/6) or 65 mg/m2 (UGT1A1*28 6/7)&#xD;
Raltitrexed: 3 mg/m2 q3w</description>
  </arm_group>
  <arm_group>
    <arm_group_label>rhIL-11 arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>rhIL-11: 50 ug/kg, subcutaneous injection, per day. (stopped as soon as the platelet count rises to normal)&#xD;
Concurrent Chemoradiotherapy:&#xD;
Radiation: judged according to the tumor site and radiotherapy purpose.&#xD;
Irinotecan: 80 mg/m2 (UGT1A1*28 6/6) or 65 mg/m2 (UGT1A1*28 6/7)&#xD;
Raltitrexed: 3 mg/m2 q3w</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>rhTPO</intervention_name>
    <description>rhTPO 300u/kg, subcutaneous injection, qd</description>
    <arm_group_label>rhTPO arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>irinotecan</intervention_name>
    <description>80mg/m2 (UGT1A1*28 6/6) or 65mg/m2 (UGT1A1*28 6/7)</description>
    <arm_group_label>rhIL-11 arm</arm_group_label>
    <arm_group_label>rhTPO arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Raltitrexed</intervention_name>
    <description>3mg/m2 q3w</description>
    <arm_group_label>rhIL-11 arm</arm_group_label>
    <arm_group_label>rhTPO arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>radiotherapy</intervention_name>
    <description>in the use of intensity-modulated radiotherapy (IMRT) technology, the dose is judged according to the tumor site and radiotherapy purpose.</description>
    <arm_group_label>rhIL-11 arm</arm_group_label>
    <arm_group_label>rhTPO arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>rhIL-11</intervention_name>
    <description>rhIL-11 50ug/kg, subcutaneous injection, qd</description>
    <arm_group_label>rhIL-11 arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The primary tumor is colorectal cancer, histologically proved recurrence or metastasis&#xD;
             disease, or pelvic relapse within 6 months after oxaliplatin-based adjuvant&#xD;
             chemotherapy.&#xD;
&#xD;
          -  Not suitable for re-use of oxaliplatin and fluorouracil.&#xD;
&#xD;
          -  No medication history of irinotecan.&#xD;
&#xD;
          -  Lesions evaluable, and has indications for radiotherapy.&#xD;
&#xD;
          -  UGT1A1*28 gene phenotype is 6/6 or 6/7&#xD;
&#xD;
          -  Karnofsky physical condition score ≥ 70&#xD;
&#xD;
          -  Baseline platelet counts are 25-75×10^9/L, other bone marrow reserve and liver and&#xD;
             kidney function meet the requirements of radiotherapy&#xD;
&#xD;
          -  Able to follow the program during the study period&#xD;
&#xD;
          -  Sign the informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or breastfeeding women&#xD;
&#xD;
          -  Those with other history of malignant disease in the past 5 years, except for cured&#xD;
             skin cancer and cervical carcinoma in situ&#xD;
&#xD;
          -  If there is an uncontrolled history of epilepsy, central nervous system disease or&#xD;
             mental disorder, the investigator may determine that the clinical severity may hinder&#xD;
             the signing of informed consent or affect the patient's oral medication compliance.&#xD;
&#xD;
          -  Clinically severe (ie, active) heart disease, such as symptomatic coronary heart&#xD;
             disease, New York Heart Association (NYHA) class II or more severe congestive heart&#xD;
             failure or severe arrhythmia requiring medication intervention (see appendix 12), or a&#xD;
             history of myocardial infarction in the last 12 months&#xD;
&#xD;
          -  Organ transplantation requires immunosuppressive therapy&#xD;
&#xD;
          -  Severe uncontrolled recurrent infections, or other serious uncontrolled concomitant&#xD;
             diseases&#xD;
&#xD;
          -  Subject blood routine and biochemical indicators do not meet the following criteria:&#xD;
             hemoglobin ≥ 90g / L; absolute neutrophil count (ANC) ≥ 1.5 × 109 / L; Alanine&#xD;
             transaminase (ALT), aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of&#xD;
             normal; alkaline phosphatase (ALP) ≤2.5 times the normal upper limit; serum total&#xD;
             bilirubin &lt;1.5 times the normal upper limit; serum creatinine &lt;1 times the normal&#xD;
             upper limit; serum albumin ≥ 30g / L&#xD;
&#xD;
          -  Anyone who is allergic to any research medication&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zhen Zhang, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Fudan University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ji Zhu, MD</last_name>
    <phone>+86-2164175590</phone>
    <phone_ext>81607</phone_ext>
    <email>leo.zhu@126.com</email>
  </overall_contact>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 19, 2019</study_first_submitted>
  <study_first_submitted_qc>January 28, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <last_update_submitted>January 28, 2019</last_update_submitted>
  <last_update_submitted_qc>January 28, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 30, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fudan University</investigator_affiliation>
    <investigator_full_name>Zhu Ji</investigator_full_name>
    <investigator_title>professor</investigator_title>
  </responsible_party>
  <keyword>Recombinant human interleukin-11</keyword>
  <keyword>Recombinant human thrombopoietin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
    <mesh_term>Thrombocytopenia</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Irinotecan</mesh_term>
    <mesh_term>Raltitrexed</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03823079
org study id: FDRT-009
nct id: NCT03823079
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This randomized controlled clinical phase II study was designed to compare the effect of
      rhTPO with rhIL-11 in improving thrombocytopenia in patients with recurrent colorectal cancer
      who underwent radiotherapy and with thrombocytopenia.
Most patients with recurrent CRC have undergone a six-month postoperative adjuvant
      chemotherapy with oxaliplatin plus fluorouracil. Although the main dose-limiting side effect
      of oxaliplatin is neurotoxicity, with the widespread use of this drug, there are more and
      more reports that oxaliplatin is discontinued because of thrombocytopenia, which increases
      the risk of bleeding, rate of blood transfusion needs and length of stay. On the other hand,
      patients undergoing pelvic radiotherapy may also experience significant bone marrow
      suppression because flat bones such as the tibia may be exposed to high doses radiation. Low
      platelet counts is an urgent problem to be solved in order to give adequate quantitative
      radiotherapy. This randomized controlled clinical phase II study was designed to compare the
      effect of rhTPO with rhIL-11 in improving thrombocytopenia in patients with recurrent
      colorectal cancer who underwent radiotherapy and with thrombocytopenia, thus providing more
      evidence in clinical practice.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: the rate of recovery of platelet accounts
time frame: From date of chemoradiation until the date of first documented recovery, assessed up to 6 months
measure: the duration after returning to normal
time frame: From date of first documented recovery until the date of first documented decrease of platelet accounts, assessed up to 6 months
measure: cycles of concurrent chemotherapy patients received during radiotherapy
time frame: through chemoradiation, an average of 5 weeks
measure: change of participant quality of life during treatment as assessed by EORTC-quality of life questionnaire-C30
time frame: at the beginning and the end of chemoradiation.
measure: change of participant quality of life during treatment as assessed by EuroQol-5 dimensional (EQ-5D) questionnaire
time frame: at the beginning and the end of chemoradiation.
measure: the rate of pathological complete response.
time frame: Surgery scheduled 6-8 weeks after the end of chemoradiation
description: pathological complete response (pCR) was defined no viable cancer cell under the examination of surgical resection specimen.
arm group label: rhTPO arm
arm group type: Experimental
description: rhTPO: 300 u/kg, subcutaneous injection, per day. (stopped as soon as the platelet count rises to normal)
Concurrent Chemoradiotherapy:
Radiation: judged according to the tumor site and radiotherapy purpose.
Irinotecan: 80 mg/m2 (UGT1A1*28 6/6) or 65 mg/m2 (UGT1A1*28 6/7)
Raltitrexed: 3 mg/m2 q3w
arm group label: rhIL-11 arm
arm group type: Active Comparator
description: rhIL-11: 50 ug/kg, subcutaneous injection, per day. (stopped as soon as the platelet count rises to normal)
Concurrent Chemoradiotherapy:
Radiation: judged according to the tumor site and radiotherapy purpose.
Irinotecan: 80 mg/m2 (UGT1A1*28 6/6) or 65 mg/m2 (UGT1A1*28 6/7)
Raltitrexed: 3 mg/m2 q3w
intervention type: Drug
intervention name: rhTPO
description: rhTPO 300u/kg, subcutaneous injection, qd
arm group label: rhTPO arm
intervention type: Drug
intervention name: irinotecan
description: 80mg/m2 (UGT1A1*28 6/6) or 65mg/m2 (UGT1A1*28 6/7)
arm group label: rhIL-11 arm
arm group label: rhTPO arm
intervention type: Drug
intervention name: Raltitrexed
description: 3mg/m2 q3w
arm group label: rhIL-11 arm
arm group label: rhTPO arm
intervention type: Radiation
intervention name: radiotherapy
description: in the use of intensity-modulated radiotherapy (IMRT) technology, the dose is judged according to the tumor site and radiotherapy purpose.
arm group label: rhIL-11 arm
arm group label: rhTPO arm
intervention type: Drug
intervention name: rhIL-11
description: rhIL-11 50ug/kg, subcutaneous injection, qd
arm group label: rhIL-11 arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Zhen Zhang, MD
role: Study Chair
affiliation: Fudan University
last name: Ji Zhu, MD
phone: +86-2164175590
phone ext: 81607
email: leo.zhu@126.com
responsible party type: Principal Investigator
investigator affiliation: Fudan University
investigator full name: Zhu Ji
investigator title: professor
mesh term: Colorectal Neoplasms
mesh term: Thrombocytopenia
mesh term: Recurrence
mesh term: Irinotecan
mesh term: Raltitrexed
sharing ipd: No