<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/NCT04443543</url>
  </required_header>
  <id_info>
    <org_study_id>CARTOnG-2001</org_study_id>
    <nct_id>NCT04443543</nct_id>
  </id_info>
  <brief_title>An Adaptive-design Prospective Cohort Study of Watch and Wait Strategy in Patients With Locally Advanced Rectal Cancer</brief_title>
  <official_title>Watch and Wait Strategy in Patients With Locally Advanced Rectal Cancer After Neoadjuvant Chemoradiotherapy: A Multi-centre, Adaptive-design, Phase II Prospective Cohort Study</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>
      The study is designed to test the hypothesis that the clinical complete response (CCR) rate&#xD;
      of patients with locally advanced rectal cancer (LARC) treated with neoadjuvant&#xD;
      chemoradiotherapy will increase after an adaptive-design paradigm, as well as the rate of&#xD;
      2-year organ preservation, recurrence, quality of life, DFS and OS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. Primary objective:&#xD;
&#xD;
           Evaluate the CCR rate of low rectal cancer using adaptive and optimized chemotherapy and&#xD;
           radiotherapy strategies (all population and dMMR/MSI-H subgroup)&#xD;
&#xD;
        2. Secondary objectives:&#xD;
&#xD;
           2.1 Evaluate the 2-year anal preservation rate, recurrence rate, quality of life, DFS&#xD;
           and OS 2.2 Explore the subgroup of patients suitable for observation.&#xD;
&#xD;
        3. Outline:&#xD;
&#xD;
      Patients after long-course chemoradiation are grouped based on their MSI-H/dMMR status. For&#xD;
      patients with MSI-H/dMMR, consolidation immunotherapy of Tislelizumab (BGB-A317) will be&#xD;
      assigned. For patients with MSS/pMMR, consolidation chemotherapy will be given according to&#xD;
      their tumor response. After completion of consolidation therapy, those who reach clinical&#xD;
      complete response will receive organ preservation (watch and wait) strategy in place of&#xD;
      radical surgery. During treatment, once local regrowth occurs or poor tumor response, total&#xD;
      mesorectal excision (TME) surgery will be performed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">June 22, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2026</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2026</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>clinical complete response rate</measure>
    <time_frame>two weeks after completion of CRT or consolidation chemotherapy.</time_frame>
    <description>After nCRT, the lesions of rectal completely respond. Tumor residue cannot be found by digital rectal examination, endoscopic biopsy and radiology.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>2y-anal preservation rate</measure>
    <time_frame>2 years</time_frame>
    <description>2-year anal preservation rate will be defined as the percentage of patients alive without receiving abdominoperineal resection at 2 years measured from the date of completion of CRT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>2y-local recurrence rate</measure>
    <time_frame>2 years</time_frame>
    <description>2-year local recurrence rate will be defined as the percentage of patients alive developing local recurrence at 2 years measured from the date of completion of CRT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Impact of participants' quality of life</measure>
    <time_frame>2 years</time_frame>
    <description>quality of life is evaluated according to EORTC C-30 questionnare.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>overall survival</measure>
    <time_frame>3 years</time_frame>
    <description>3-year OS will be defined as the percentage of patients alive at 3 years measured from the date of completion of CRT.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">222</enrollment>
  <condition>Rectal Cancer</condition>
  <arm_group>
    <arm_group_label>Arm 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm 1 includes patients with MSS/pMMR. In this arm, patients receive consolidation chemotherapy after neoadjuvant chemoradiation (nCRT). The chemotherapy regimens either XELIRI or FOLFIRINOX, and the cycles of chemotherapy depend on patient tumor responses. For patients who reach cCR will enter the &quot;W&amp;W&quot; cohort and omit radical surgery, while those without cCR will receive radical surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Arm 2 includes patients with MSI-H/dMMR status. In this arm, patients receive consolidation immunotherapy of 3 cycles of tislelizumab after nCRT. For patients who reach cCR will enter the &quot;W&amp;W&quot; cohort and omit radical surgery, while those without cCR will receive radical surgery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine (Xeloda) Pharmacogenetic Test Reagents</intervention_name>
    <description>CRT: 625mg/m2 bid Monday-Friday per week XELIRI: 1000mg/m2 bid d1-14</description>
    <arm_group_label>Arm 1</arm_group_label>
    <arm_group_label>Arm 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>irinotecan</intervention_name>
    <description>CRT:80mg/m2 (UGT1A1*28 6/6) or 65mg/m2 (UGT1A1*28 6/7) XELIRI: 200mg/m2 bid d1 FOLFIRINOX: 150mg/m2 d1</description>
    <arm_group_label>Arm 1</arm_group_label>
    <arm_group_label>Arm 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>IMRT</intervention_name>
    <description>Pelvic Radiation: 50Gy/25Fx</description>
    <arm_group_label>Arm 1</arm_group_label>
    <arm_group_label>Arm 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxaliplatin</intervention_name>
    <description>FOLFIRINOX: 85mg/m2 d1</description>
    <arm_group_label>Arm 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>5Fluorouracil</intervention_name>
    <description>FOLFIRINOX: 400mg/m2 iv d1bolus, 2400mg/m2 ivgtt 46h</description>
    <arm_group_label>Arm 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tislelizumab</intervention_name>
    <description>200mg iv</description>
    <arm_group_label>Arm 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  pathological confirmed adenocarcinoma&#xD;
&#xD;
          -  clinical stage T2-4 and/or N+, inappropriate for local excision&#xD;
&#xD;
          -  the distance from anal verge less than 5 cm, or considered inappropriate for anal&#xD;
             preservation by surgeons.&#xD;
&#xD;
          -  Strong desire to preserve the anus, able to receive close surveillance for at least 2&#xD;
             years after chemoradiotherapy.&#xD;
&#xD;
          -  without distance metastases&#xD;
&#xD;
          -  aged between 18 to 75 years old.&#xD;
&#xD;
          -  performance status score: 0~1&#xD;
&#xD;
          -  UGT1A1*28 6/6 or 6/7&#xD;
&#xD;
          -  sign the inform consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  pregnancy or breast-feeding women&#xD;
&#xD;
          -  serious medical illness&#xD;
&#xD;
          -  difficult to achieve complete response assessed by current evidence: the maximal&#xD;
             diameter of tumor &gt;10cm; the maximal diameter of lateral lymph node &gt;2cm; baseline&#xD;
             CEA&gt;=100; biopsy pathology confirmed signet ring cell carcinoma components; digital&#xD;
             rectal examination found that the tumor is peri-narrowed.&#xD;
&#xD;
          -  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;
          -  DPD deficiency&#xD;
&#xD;
          -  UGT1A1*28 7/7&#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>Ji Zhu</last_name>
    <phone>+86-2164175590</phone>
    <phone_ext>81607</phone_ext>
    <email>leo.zhu@126.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Fudan University Shanghai Cancer Cencer</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 20, 2020</study_first_submitted>
  <study_first_submitted_qc>June 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 23, 2020</study_first_posted>
  <last_update_submitted>June 27, 2020</last_update_submitted>
  <last_update_submitted_qc>June 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 30, 2020</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>principle investigator</investigator_title>
  </responsible_party>
  <keyword>Chemoradiotherapy</keyword>
  <keyword>organ preservation</keyword>
  <keyword>watch and wait</keyword>
  <keyword>irinotecan</keyword>
  <keyword>Tislelizumab</keyword>
  <keyword>capecitabine</keyword>
  <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>Fluorouracil</mesh_term>
    <mesh_term>Capecitabine</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
    <mesh_term>Irinotecan</mesh_term>
    <mesh_term>Tislelizumab</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/NCT04443543
org study id: CARTOnG-2001
nct id: NCT04443543
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The study is designed to test the hypothesis that the clinical complete response (CCR) rate
      of patients with locally advanced rectal cancer (LARC) treated with neoadjuvant
      chemoradiotherapy will increase after an adaptive-design paradigm, as well as the rate of
      2-year organ preservation, recurrence, quality of life, DFS and OS.
1. Primary objective:

           Evaluate the CCR rate of low rectal cancer using adaptive and optimized chemotherapy and
           radiotherapy strategies (all population and dMMR/MSI-H subgroup)

        2. Secondary objectives:

           2.1 Evaluate the 2-year anal preservation rate, recurrence rate, quality of life, DFS
           and OS 2.2 Explore the subgroup of patients suitable for observation.

        3. Outline:

      Patients after long-course chemoradiation are grouped based on their MSI-H/dMMR status. For
      patients with MSI-H/dMMR, consolidation immunotherapy of Tislelizumab (BGB-A317) will be
      assigned. For patients with MSS/pMMR, consolidation chemotherapy will be given according to
      their tumor response. After completion of consolidation therapy, those who reach clinical
      complete response will receive organ preservation (watch and wait) strategy in place of
      radical surgery. During treatment, once local regrowth occurs or poor tumor response, total
      mesorectal excision (TME) surgery will be performed.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: clinical complete response rate
time frame: two weeks after completion of CRT or consolidation chemotherapy.
description: After nCRT, the lesions of rectal completely respond. Tumor residue cannot be found by digital rectal examination, endoscopic biopsy and radiology.
measure: 2y-anal preservation rate
time frame: 2 years
description: 2-year anal preservation rate will be defined as the percentage of patients alive without receiving abdominoperineal resection at 2 years measured from the date of completion of CRT.
measure: 2y-local recurrence rate
time frame: 2 years
description: 2-year local recurrence rate will be defined as the percentage of patients alive developing local recurrence at 2 years measured from the date of completion of CRT.
measure: Impact of participants' quality of life
time frame: 2 years
description: quality of life is evaluated according to EORTC C-30 questionnare.
measure: overall survival
time frame: 3 years
description: 3-year OS will be defined as the percentage of patients alive at 3 years measured from the date of completion of CRT.
arm group label: Arm 1
arm group type: Experimental
description: Arm 1 includes patients with MSS/pMMR. In this arm, patients receive consolidation chemotherapy after neoadjuvant chemoradiation (nCRT). The chemotherapy regimens either XELIRI or FOLFIRINOX, and the cycles of chemotherapy depend on patient tumor responses. For patients who reach cCR will enter the "W&W" cohort and omit radical surgery, while those without cCR will receive radical surgery.
arm group label: Arm 2
arm group type: Experimental
description: Arm 2 includes patients with MSI-H/dMMR status. In this arm, patients receive consolidation immunotherapy of 3 cycles of tislelizumab after nCRT. For patients who reach cCR will enter the "W&W" cohort and omit radical surgery, while those without cCR will receive radical surgery.
intervention type: Drug
intervention name: Capecitabine (Xeloda) Pharmacogenetic Test Reagents
description: CRT: 625mg/m2 bid Monday-Friday per week XELIRI: 1000mg/m2 bid d1-14
arm group label: Arm 1
arm group label: Arm 2
intervention type: Drug
intervention name: irinotecan
description: CRT:80mg/m2 (UGT1A1*28 6/6) or 65mg/m2 (UGT1A1*28 6/7) XELIRI: 200mg/m2 bid d1 FOLFIRINOX: 150mg/m2 d1
arm group label: Arm 1
arm group label: Arm 2
intervention type: Radiation
intervention name: IMRT
description: Pelvic Radiation: 50Gy/25Fx
arm group label: Arm 1
arm group label: Arm 2
intervention type: Drug
intervention name: Oxaliplatin
description: FOLFIRINOX: 85mg/m2 d1
arm group label: Arm 1
intervention type: Drug
intervention name: 5Fluorouracil
description: FOLFIRINOX: 400mg/m2 iv d1bolus, 2400mg/m2 ivgtt 46h
arm group label: Arm 1
intervention type: Drug
intervention name: Tislelizumab
description: 200mg iv
arm group label: Arm 2
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Ji Zhu
phone: +86-2164175590
phone ext: 81607
email: leo.zhu@126.com
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Fudan University
investigator full name: Zhu Ji
investigator title: principle investigator
mesh term: Rectal Neoplasms
mesh term: Fluorouracil
mesh term: Capecitabine
mesh term: Oxaliplatin
mesh term: Irinotecan
mesh term: Tislelizumab
sharing ipd: No