xml: <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/NCT05980689</url>
    </required_header>
    <id_info>
      <org_study_id>B2022-766-01</org_study_id>
      <nct_id>NCT05980689</nct_id>
    </id_info>
    <brief_title>Combination of AK104 and Neoadjuvant Chemoradiotherapy in pMMR/MSS Locally Advanced Rectal Cancer</brief_title>
    <official_title>A Phase II Trial of AK104 Combined With Neoadjuvant Chemoradiotherapy in Proficient Mismatch Repair/Microsatellite Stable Locally Advanced Rectal Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Sun Yat-sen University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Akeso</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
      <collaborator>
        <agency>Haplox Biotechnology Co., Ltd.</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Sun Yat-sen 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>
        This is an open-label, single-arm study to investigate the efficacy and safety of AK104 (an&#xD;
        Anti-PD1 and Anti-CTLA4 Bispecific Antibody) and neoadjuvant chemoradiotherapy in patients&#xD;
        with pMMR/MSS locally advanced rectal cancer.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The study evaluates the addition of AK104(an Anti-PD1 and Anti-CTLA4 Bispecific Antibody) in&#xD;
        neoadjuvant chemoradiotherapy in proficient Mismatch Repair (pMMR) /Microsatellite Stable&#xD;
        (MSS) locally advanced rectal cancer (LARC). A total of 33 pMMR/MSS LARC patients will&#xD;
        receive long-course chemoradiotherapy plus 2 cycles of AK104, followed by another 3 cycles of&#xD;
        AK104, finally received clinical routine manage. The tumor response to treatment, adverse&#xD;
        effects and long-term prognosis will be analyzed.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">January 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">June 30, 2024</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>Complete response (CR) rate</measure>
      <time_frame>an average of 6 months.</time_frame>
      <description>Rate of complete response (CR), including pathologic complete response (pCR) and clinical complete response (cCR).</description>
    </primary_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>Adverse effects according to CTCAE 5.0</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rate of Major pathologic response and tumor regression grade distribution</measure>
      <time_frame>an average of 1 year.</time_frame>
      <description>Rate of Major pathologic response and tumor regression grade distribution</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rate of surgical complications</measure>
      <time_frame>The surgery was scheduled 2-4 weeks after the end of neoadjuvant therapy. And the surgical complications were assessed up to 1 year from the surgery.</time_frame>
      <description>Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.</description>
    </secondary_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 60 months.</time_frame>
      <description>5 year overall survival rate</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Long-term anal function</measure>
      <time_frame>1.5 year after diagnosis</time_frame>
      <description>Long-term anal function was evaluated using the Wexner Continence Grading Scale ,the score being calculated after the patients' completion of a daily defecatory questionnaire. Range is from 0 (normal continence) to 20 (maximum incontinence with maximum disturbance of lifestyle)</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">33</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 33 pMMR/MSS LARC patients will receive long-course chemoradiotherapy plus 2 cycles of AK104, followed by another 3 cycles of AK104, finally received clinical routine manage.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>AK104</intervention_name>
      <description>During neo-CRT: 2 cycles of AK104, 10mg/kg d1 q3w. After neo-CRT: 3 cycles of AK104, 10mg/kg d1 q3w.</description>
      <arm_group_label>Treatment Arm</arm_group_label>
      <other_name>Cadonilimab</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Capecitabine</intervention_name>
      <description>During neo-CRT: 825mg/m2 bid Monday-Friday per week</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. Age 18-75&#xD;
  &#xD;
            2. ECOG 0-1&#xD;
  &#xD;
            3. Rectal adenocarcinoma&#xD;
  &#xD;
            4. cT3-4aNany or cT1-4aN+&#xD;
  &#xD;
            5. No distant metastasis&#xD;
  &#xD;
            6. Location ≤15 cm from the anal verge&#xD;
  &#xD;
            7. the MSI status is MSS and pMMR&#xD;
  &#xD;
            8. Sufficient bone marrow, kidney and liver function&#xD;
  &#xD;
            9. No previous surgery of the rectum, no previous chemotherapy, no previous pelvic&#xD;
               radiation, no previous biotherapy, no immunotherapy&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. bowel obstruction&#xD;
  &#xD;
            2. Distant metastasis&#xD;
  &#xD;
            3. Severe arrhythmia, cardiac dysfunction (NYHA grade III or IV )&#xD;
  &#xD;
            4. Uncontrollable severe hypertesion&#xD;
  &#xD;
            5. Active severe infection&#xD;
  &#xD;
            6. Cachexia, organ dysfunction&#xD;
  &#xD;
            7. Previous pelvic radiotherapy or chemotherapy&#xD;
  &#xD;
            8. Multiple primary cancers&#xD;
  &#xD;
            9. Epileptic seizures&#xD;
  &#xD;
           10. Malignant history within 5 years, except cervical carcinoma in situ or cutaneous basal&#xD;
               cell carcinoma&#xD;
  &#xD;
           11. Persons deprived of liberty or under guardianship&#xD;
  &#xD;
           12. Impossibility for compliance to follow-up&#xD;
  &#xD;
           13. Certain or suspicious allergy to research drug&#xD;
  &#xD;
           14. Pregnant or breast-feeding woman&#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_contact>
      <last_name>WeiWei Xiao</last_name>
      <phone>8613710390520</phone>
      <phone_ext>8613710390520</phone_ext>
      <email>xiaoww@sysucc.org.cn</email>
    </overall_contact>
    <location>
      <facility>
        <name>Sun Yat-sen University Cancer Center</name>
        <address>
          <city>Guangzhou</city>
          <state>Guangdong</state>
          <zip>510060</zip>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 26, 2023</study_first_submitted>
    <study_first_submitted_qc>August 5, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 8, 2023</study_first_posted>
    <last_update_submitted>August 5, 2023</last_update_submitted>
    <last_update_submitted_qc>August 5, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
      <investigator_full_name>WeiWei Xiao</investigator_full_name>
      <investigator_title>Chief physician</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>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05980689
  org study id: B2022-766-01
  nct id: NCT05980689
  lead sponsor: 
  collaborator: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: No
  This is an open-label, single-arm study to investigate the efficacy and safety of AK104 (an
        Anti-PD1 and Anti-CTLA4 Bispecific Antibody) and neoadjuvant chemoradiotherapy in patients
        with pMMR/MSS locally advanced rectal cancer.
  The study evaluates the addition of AK104(an Anti-PD1 and Anti-CTLA4 Bispecific Antibody) in
        neoadjuvant chemoradiotherapy in proficient Mismatch Repair (pMMR) /Microsatellite Stable
        (MSS) locally advanced rectal cancer (LARC). A total of 33 pMMR/MSS LARC patients will
        receive long-course chemoradiotherapy plus 2 cycles of AK104, followed by another 3 cycles of
        AK104, finally received clinical routine manage. The tumor response to treatment, 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: Complete response (CR) rate
  time frame: an average of 6 months.
  description: Rate of complete response (CR), including pathologic complete response (pCR) and clinical complete response (cCR).
  measure: Adverse effects
  time frame: From date of randomization until the date of death from any cause, assessed up to 5 years
  description: Adverse effects according to CTCAE 5.0
  measure: Rate of Major pathologic response and tumor regression grade distribution
  time frame: an average of 1 year.
  description: Rate of Major pathologic response and tumor regression grade distribution
  measure: Rate of surgical complications
  time frame: The surgery was scheduled 2-4 weeks after the end of neoadjuvant therapy. And the surgical complications were assessed up to 1 year from the surgery.
  description: Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.
  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 60 months.
  description: 5 year overall survival rate
  measure: Long-term anal function
  time frame: 1.5 year after diagnosis
  description: Long-term anal function was evaluated using the Wexner Continence Grading Scale ,the score being calculated after the patients' completion of a daily defecatory questionnaire. Range is from 0 (normal continence) to 20 (maximum incontinence with maximum disturbance of lifestyle)
  arm group label: Treatment Arm
  arm group type: Experimental
  description: A total of 33 pMMR/MSS LARC patients will receive long-course chemoradiotherapy plus 2 cycles of AK104, followed by another 3 cycles of AK104, finally received clinical routine manage.
  intervention type: Drug
  intervention name: AK104
  description: During neo-CRT: 2 cycles of AK104, 10mg/kg d1 q3w. After neo-CRT: 3 cycles of AK104, 10mg/kg d1 q3w.
  arm group label: Treatment Arm
  other name: Cadonilimab
  intervention type: Drug
  intervention name: Capecitabine
  description: During neo-CRT: 825mg/m2 bid Monday-Friday per week
  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: 75 Years
  healthy volunteers: No
  last name: WeiWei Xiao
  phone: 8613710390520
  phone ext: 8613710390520
  email: xiaoww@sysucc.org.cn
  facility: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Sun Yat-sen University
  investigator full name: WeiWei Xiao
  investigator title: Chief physician
  mesh term: Rectal Neoplasms
  mesh term: Capecitabine
  sharing ipd: Undecided