<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/NCT04411537</url>
  </required_header>
  <id_info>
    <org_study_id>FDRT-2019-97-1731</org_study_id>
    <nct_id>NCT04411537</nct_id>
  </id_info>
  <brief_title>The Combination of Immunotherapy and Neoadjuvant Chemoradiotherapy in MSS Locally Advanced Rectal Cancer</brief_title>
  <official_title>A Phase II Trial of Immunotherapy Combined With Neoadjuvant Chemoradiotherapy in Microsatellite Stable Locally Advanced Rectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fudan University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fudan University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study evaluates the addition of immunotherapy of PD-1 antibody in neoadjuvant&#xD;
      chemoradiotherapy in microsatellite stable (MSS) locally advanced rectal cancer (LARC). A&#xD;
      total of 50 MSS LARC patients will receive 2 cycles of PD-1 antibody, followed by&#xD;
      capecitabine plus irinotecan radiosensitized neoadjuvant chemoradiotherapy, and another 3&#xD;
      cycles of PD-1 antibody, finally received the total mesorectal excision (TME) and 6 cycles of&#xD;
      adjuvant chemotherapy of XELOX. The tumor response grade, adverse effects and long-term&#xD;
      prognosis will be analyzed.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">July 1, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">April 30, 2022</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>Pathologic Complete Response Rate</measure>
    <time_frame>The pathologic complete response rate was evaluated after surgery, which was scheduled 7-8 weeks after the end of chemoradiotherapy</time_frame>
    <description>Pathologic Complete Response Rate</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease free survival</measure>
    <time_frame>From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.</time_frame>
    <description>3 year disease free survival rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Local recurrence free survival</measure>
    <time_frame>From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.</time_frame>
    <description>3 year local recurrence free survival rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>From date of randomization until the date of death from any cause, assessed up to 36 months.</time_frame>
    <description>3 year overall survival rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse effects</measure>
    <time_frame>From date of randomization until the date of death from any cause, assessed up to 5 years</time_frame>
    <description>Chemoradiation-related or immunotherapy-related adverse events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Surgical complications</measure>
    <time_frame>The surgery was scheduled 7-8 weeks after the end of chemoradiotherapy. And the surgical complications were assessed up to 5 years from the surgery.</time_frame>
    <description>Surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Performance Status (Zubrod-ECOG-WHO method), range 0-5. The higher scores mean a worse quality of life.</measure>
    <time_frame>From date of randomization until the date of death from any cause, assessed up to 10 years</time_frame>
    <description>Quality of life will be evaluated</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Karnofsky Performance Status, range 0-100. The higher scores mean a better quality of life.</measure>
    <time_frame>From date of randomization until the date of death from any cause, assessed up to 10 years</time_frame>
    <description>Quality of life will be evaluated</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life Scale, range 0-60. It evaluates the quality of life from 12 aspects, including appetite, mental status, sleep quality, fatigue, etc. The higher scores mean a better quality of life.</measure>
    <time_frame>From date of randomization until the date of death from any cause, assessed up to 10 years</time_frame>
    <description>Quality of life will be evaluated</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Locally Advanced Rectal Cancer</condition>
  <arm_group>
    <arm_group_label>Treatment Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A total of 50 MSS LARC patients will receive 2 cycles of PD-1 antibody, followed by capecitabine plus irinotecan radiosensitized neoadjuvant chemoradiotherapy, and another 3 cycles of PD-1 antibody, finally received the total mesorectal excision (TME) and 6 cycles of adjuvant chemotherapy of XELOX.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PD-1 antibody</intervention_name>
    <description>Before neo-CRT: 2 cycles of PD-1 antibody, 240mg d1 q2w. After neo-CRT: 3 cycles of PD-1 antibody, 240mg d1 q2w.</description>
    <arm_group_label>Treatment Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine</intervention_name>
    <description>During neo-CRT: 625mg/m2 bid Monday-Friday per week</description>
    <arm_group_label>Treatment Arm</arm_group_label>
    <other_name>Xeloda</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Irinotecan</intervention_name>
    <description>During neo-CRT: 80mg/m2 qw (UGT1A1*28 6/6) or 65mg/m2 qw (UGT1A1*28 6/7)</description>
    <arm_group_label>Treatment Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Neoadjuvant Radiotherapy</intervention_name>
    <description>IMRT DT: 50Gy/25Fx</description>
    <arm_group_label>Treatment Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. pathological confirmed adenocarcinoma&#xD;
&#xD;
          2. clinical stage T3-4 and/or N+&#xD;
&#xD;
          3. the distance from anal verge less than 12 cm&#xD;
&#xD;
          4. without distance metastases&#xD;
&#xD;
          5. age 18-70 years old, female and male&#xD;
&#xD;
          6. KPS &gt;=70&#xD;
&#xD;
          7. UGT1A1*28 6/6 or 6/7&#xD;
&#xD;
          8. the MSI status is MSS or p-MMR&#xD;
&#xD;
          9. without previous anti-cancer therapy or immunotherapy&#xD;
&#xD;
         10. with good compliance&#xD;
&#xD;
         11. signed the inform consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. pregnancy or breast-feeding women&#xD;
&#xD;
          2. history of other malignancies within 5 years&#xD;
&#xD;
          3. serious medical illness, such as severe mental disorders, cardiac disease,&#xD;
             uncontrolled infection, etc.&#xD;
&#xD;
          4. immunodeficiency disease or long-term using of immunosuppressive agents&#xD;
&#xD;
          5. baseline blood and biochemical indicators do not meet the following criteria:&#xD;
             neutrophils≥1.5×10^9/L, Hb≥90g/L, PLT≥100×10^9/L, ALT/AST ≤2.5 ULN, Cr≤ 1 ULN&#xD;
&#xD;
          6. DPD deficiency&#xD;
&#xD;
          7. UGT1A1*28 7/7&#xD;
&#xD;
          8. the MSI status is MSI-H or d-MMR&#xD;
&#xD;
          9. allergic to any component of the therapy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>zhen zhang, M.D, PH.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fudan University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>zhen zhang, M.D, PH.D</last_name>
    <phone>18801735029</phone>
    <phone_ext>18801735029</phone_ext>
    <email>zhen_zhang@fudan.edu.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>Zhen Zhang</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
    <contact>
      <last_name>Zhen Zhang, M.D, PH.D</last_name>
      <phone>18801735029</phone>
      <phone_ext>18801735029</phone_ext>
      <email>zhen_zhang@fudan.edu.cn</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>May 10, 2020</study_first_submitted>
  <study_first_submitted_qc>June 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>June 1, 2020</last_update_submitted>
  <last_update_submitted_qc>June 1, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 2, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fudan University</investigator_affiliation>
    <investigator_full_name>Zhen Zhang</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>Rectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Capecitabine</mesh_term>
    <mesh_term>Irinotecan</mesh_term>
    <mesh_term>Antibodies</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/NCT04411537
org study id: FDRT-2019-97-1731
nct id: NCT04411537
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The study evaluates the addition of immunotherapy of PD-1 antibody in neoadjuvant
      chemoradiotherapy in microsatellite stable (MSS) locally advanced rectal cancer (LARC). A
      total of 50 MSS LARC patients will receive 2 cycles of PD-1 antibody, followed by
      capecitabine plus irinotecan radiosensitized neoadjuvant chemoradiotherapy, and another 3
      cycles of PD-1 antibody, finally received the total mesorectal excision (TME) and 6 cycles of
      adjuvant chemotherapy of XELOX. The tumor response grade, adverse effects and long-term
      prognosis will be analyzed.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pathologic Complete Response Rate
time frame: The pathologic complete response rate was evaluated after surgery, which was scheduled 7-8 weeks after the end of chemoradiotherapy
description: Pathologic Complete Response Rate
measure: Disease free survival
time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.
description: 3 year disease free survival rate
measure: Local recurrence free survival
time frame: From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.
description: 3 year local recurrence free survival rate
measure: Overall survival
time frame: From date of randomization until the date of death from any cause, assessed up to 36 months.
description: 3 year overall survival rate
measure: Adverse effects
time frame: From date of randomization until the date of death from any cause, assessed up to 5 years
description: Chemoradiation-related or immunotherapy-related adverse events
measure: Surgical complications
time frame: The surgery was scheduled 7-8 weeks after the end of chemoradiotherapy. And the surgical complications were assessed up to 5 years from the surgery.
description: Surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.
measure: Performance Status (Zubrod-ECOG-WHO method), range 0-5. The higher scores mean a worse quality of life.
time frame: From date of randomization until the date of death from any cause, assessed up to 10 years
description: Quality of life will be evaluated
measure: Karnofsky Performance Status, range 0-100. The higher scores mean a better quality of life.
time frame: From date of randomization until the date of death from any cause, assessed up to 10 years
description: Quality of life will be evaluated
measure: Quality of Life Scale, range 0-60. It evaluates the quality of life from 12 aspects, including appetite, mental status, sleep quality, fatigue, etc. The higher scores mean a better quality of life.
time frame: From date of randomization until the date of death from any cause, assessed up to 10 years
description: Quality of life will be evaluated
arm group label: Treatment Arm
arm group type: Experimental
description: A total of 50 MSS LARC patients will receive 2 cycles of PD-1 antibody, followed by capecitabine plus irinotecan radiosensitized neoadjuvant chemoradiotherapy, and another 3 cycles of PD-1 antibody, finally received the total mesorectal excision (TME) and 6 cycles of adjuvant chemotherapy of XELOX.
intervention type: Drug
intervention name: PD-1 antibody
description: Before neo-CRT: 2 cycles of PD-1 antibody, 240mg d1 q2w. After neo-CRT: 3 cycles of PD-1 antibody, 240mg d1 q2w.
arm group label: Treatment Arm
intervention type: Drug
intervention name: Capecitabine
description: During neo-CRT: 625mg/m2 bid Monday-Friday per week
arm group label: Treatment Arm
other name: Xeloda
intervention type: Drug
intervention name: Irinotecan
description: During neo-CRT: 80mg/m2 qw (UGT1A1*28 6/6) or 65mg/m2 qw (UGT1A1*28 6/7)
arm group label: Treatment Arm
intervention type: Radiation
intervention name: Neoadjuvant Radiotherapy
description: IMRT DT: 50Gy/25Fx
arm group label: Treatment Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: zhen zhang, M.D, PH.D
role: Principal Investigator
affiliation: Fudan University
last name: zhen zhang, M.D, PH.D
phone: 18801735029
phone ext: 18801735029
email: zhen_zhang@fudan.edu.cn
facility: 
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Fudan University
investigator full name: Zhen Zhang
investigator title: Professor
mesh term: Rectal Neoplasms
mesh term: Capecitabine
mesh term: Irinotecan
mesh term: Antibodies