<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/NCT04423965</url>
  </required_header>
  <id_info>
    <org_study_id>TRICHEMO</org_study_id>
    <nct_id>NCT04423965</nct_id>
  </id_info>
  <brief_title>A Trial of Neoadjuvant mFOLFOXIRI Versus CRT in the EMVI Positive LARC</brief_title>
  <official_title>A Multicenter Randomized Controlled Phase II Trial of Neoadjuvant mFOLFOXIRI Versus Routine Chemoradiotherapy in the EMVI Positive Locally Advanced Rectal Cancer (TRICHEMO)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>First Affiliated Hospital of Zhejiang University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>First Affiliated Hospital of Wenzhou Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Zhejiang Cancer Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>First Affiliated Hospital of Zhejiang University</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Extramural Vascular Invasion Positive(EMVI+) is a high risk of distant metastasis for locally&#xD;
      advanced rectal cancer(LARC) after resection. The study is to evaluate the efficacy and&#xD;
      safety of FOLFOXIRI as neoadjuvant chemotherapy alone for EMVI+ LARC in contrast to the&#xD;
      efficacy of standard Chemoradiotherapy (CRT).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      It is an investigator-initiated, multicentered, randomized controlled clinical study to&#xD;
      evaluate the efficacy and safety of mFOLFOXIRI as neoadjuvant chemotherapy alone for EMVI+&#xD;
      LARC in contrast to standard chemoradiotherapy. Patients of LARC with EMVI+ evaluated by&#xD;
      pelvic magnetic resonance imaging (MRI) are enrolled in this trial. All patients will be&#xD;
      randomized divided into two groups.&#xD;
&#xD;
      Experimental group will receive 3 cycles of mFOLFOXIRI, followed to be performed MRI to&#xD;
      assess clinical response. If the tumor response is good enough (partial response or complete&#xD;
      response), the patient will receive another 3 cycles of mFOLFOXIRI then surgery. On the&#xD;
      contrary, if the tumor shows poor response (stable disease or progressive disease) or with&#xD;
      mesorectal fascia-positive or ycT4a/b after re-evaluation, radiotherapy will be performed&#xD;
      combined with capecitabine before operation. Control group will receive standard capecitabine&#xD;
      based chemoradiotherapy.&#xD;
&#xD;
      Patients with mesorectal fascia-positive or ycT4a/b after re-evaluation would receive&#xD;
      radiation before surgery, whereas responders would have immediate total mesorectal excision&#xD;
      (TME). All patients will receive 4 cycles of XELOX as adjuvant chemotherapy after TME.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 12, 2020</start_date>
  <completion_date type="Anticipated">May 1, 2025</completion_date>
  <primary_completion_date type="Anticipated">May 1, 2022</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>MFS</measure>
    <time_frame>3 years</time_frame>
    <description>metastasis free survival</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Tumor downstaging rate</measure>
    <time_frame>2 years</time_frame>
    <description>the proportion of tumor downstaging to ypT0-2N0M0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>pCR</measure>
    <time_frame>2 years</time_frame>
    <description>Pathologic complete response rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>RFS</measure>
    <time_frame>3 years</time_frame>
    <description>recurrence-free survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DFS</measure>
    <time_frame>3 years</time_frame>
    <description>disease-free survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>OS</measure>
    <time_frame>5 years</time_frame>
    <description>overall survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reported Adverse events</measure>
    <time_frame>2 years</time_frame>
    <description>The incidence of &gt;=3 grade adverse events</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">220</enrollment>
  <condition>Locally Advanced Rectal Cancer</condition>
  <arm_group>
    <arm_group_label>mFOLFOXIRI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive 6 cycles of mFOLFOXIRI</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Chemoradiotherapy(CRT)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive standard chemoradiotherapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>mFOLFOXIRI</intervention_name>
    <description>irinotecan 165 mg/m² IV day 1+ oxaliplatin 85 mg/m² IV day 1 + leucovorin 400 mg/m² day 1, fluorouracil 1200mg/m²/day *2 days (total 2400 mg/m² over 48 hours) continuous infusion starting on day 1 of each 2 weeks cycle</description>
    <arm_group_label>mFOLFOXIRI</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Chemoradiotherapy</intervention_name>
    <description>Capecitabine based chemoradiotherapy</description>
    <arm_group_label>Chemoradiotherapy(CRT)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Aged ≥ 18 to 70 years at diagnosis;&#xD;
&#xD;
          2. ECOG status 0-2;&#xD;
&#xD;
          3. Diagnosis of rectal adenocarcinoma(Distal border of the tumor must be located &lt; 12 cm&#xD;
             from the anal verge);&#xD;
&#xD;
          4. MRI examination diagnosed EMVI-positive;&#xD;
&#xD;
          5. Tumor amenable to curative resection;&#xD;
&#xD;
          6. Adequate bone marrow, hepatic and renal function as assessed by the following&#xD;
             laboratory requirements conducted within 7 days of starting study treatment: (1)&#xD;
             Neutrophilic granulocytes ≥ 3.0 x10^9/L, Platelet count ≥ 75 x 10^9/L, Hemoglobin (Hb)&#xD;
             ≥ 90g/L; (2) bilirubin ≤1.5 x the upper limit of normal (ULN),Alanine aminotransferase&#xD;
             (ALT)/Aspartate aminotransferase (AST) ≤ 2.5 x ULN; (3) Serum creatinine ≤ 1.5 x&#xD;
             ULN.No renal disease that would preclude study treatment or follow-up&#xD;
&#xD;
          7. Signed informed consent; able to comply with study and/or follow- up procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Hypersensitivity to fluorouracil, oxaliplatin or irinotecan;&#xD;
&#xD;
          2. Patient had received pelvic radiotherapy;&#xD;
&#xD;
          3. Patient had received systemic chemotherapy;&#xD;
&#xD;
          4. History of invasive colon or rectal malignancy, regardless of disease-free interval;&#xD;
&#xD;
          5. Had metastatic disease;&#xD;
&#xD;
          6. Patient had second malignant disease within 5 years;&#xD;
&#xD;
          7. Uncontrolled co-morbid illnesses or other concurrent disease;&#xD;
&#xD;
          8. Patients refused to signed informed consent.&#xD;
&#xD;
          9. Pregnant and Nursing women&#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_contact>
    <last_name>Guosheng Wu, MD</last_name>
    <phone>+8617857310313</phone>
    <phone_ext>87236858</phone_ext>
    <email>guosheng_wu@zju.edu.cn</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Weiqin Jiang, MD</last_name>
    <phone>+8615068117618</phone>
    <phone_ext>87236858</phone_ext>
    <email>1312028@zju.edu.cn</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The First Affiliated Hospital, Zhejiang University School of Medicine</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <zip>310006</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Guosheng Wu, MD</last_name>
      <phone>+8617857310313</phone>
      <phone_ext>87236858</phone_ext>
      <email>guosheng_wu@zju.edu.cn</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>June 8, 2020</study_first_submitted>
  <study_first_submitted_qc>June 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>March 21, 2021</last_update_submitted>
  <last_update_submitted_qc>March 21, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 23, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>First Affiliated Hospital of Zhejiang University</investigator_affiliation>
    <investigator_full_name>Guosheng Wu</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>
  <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/NCT04423965
org study id: TRICHEMO
nct id: NCT04423965
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Extramural Vascular Invasion Positive(EMVI+) is a high risk of distant metastasis for locally
      advanced rectal cancer(LARC) after resection. The study is to evaluate the efficacy and
      safety of FOLFOXIRI as neoadjuvant chemotherapy alone for EMVI+ LARC in contrast to the
      efficacy of standard Chemoradiotherapy (CRT).
It is an investigator-initiated, multicentered, randomized controlled clinical study to
      evaluate the efficacy and safety of mFOLFOXIRI as neoadjuvant chemotherapy alone for EMVI+
      LARC in contrast to standard chemoradiotherapy. Patients of LARC with EMVI+ evaluated by
      pelvic magnetic resonance imaging (MRI) are enrolled in this trial. All patients will be
      randomized divided into two groups.

      Experimental group will receive 3 cycles of mFOLFOXIRI, followed to be performed MRI to
      assess clinical response. If the tumor response is good enough (partial response or complete
      response), the patient will receive another 3 cycles of mFOLFOXIRI then surgery. On the
      contrary, if the tumor shows poor response (stable disease or progressive disease) or with
      mesorectal fascia-positive or ycT4a/b after re-evaluation, radiotherapy will be performed
      combined with capecitabine before operation. Control group will receive standard capecitabine
      based chemoradiotherapy.

      Patients with mesorectal fascia-positive or ycT4a/b after re-evaluation would receive
      radiation before surgery, whereas responders would have immediate total mesorectal excision
      (TME). All patients will receive 4 cycles of XELOX as adjuvant chemotherapy after TME.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: MFS
time frame: 3 years
description: metastasis free survival
measure: Tumor downstaging rate
time frame: 2 years
description: the proportion of tumor downstaging to ypT0-2N0M0
measure: pCR
time frame: 2 years
description: Pathologic complete response rate
measure: RFS
time frame: 3 years
description: recurrence-free survival
measure: DFS
time frame: 3 years
description: disease-free survival
measure: OS
time frame: 5 years
description: overall survival
measure: Reported Adverse events
time frame: 2 years
description: The incidence of >=3 grade adverse events
arm group label: mFOLFOXIRI
arm group type: Experimental
description: Patients receive 6 cycles of mFOLFOXIRI
arm group label: Chemoradiotherapy(CRT)
arm group type: Experimental
description: Patients receive standard chemoradiotherapy
intervention type: Drug
intervention name: mFOLFOXIRI
description: irinotecan 165 mg/m² IV day 1+ oxaliplatin 85 mg/m² IV day 1 + leucovorin 400 mg/m² day 1, fluorouracil 1200mg/m²/day *2 days (total 2400 mg/m² over 48 hours) continuous infusion starting on day 1 of each 2 weeks cycle
arm group label: mFOLFOXIRI
intervention type: Combination Product
intervention name: Chemoradiotherapy
description: Capecitabine based chemoradiotherapy
arm group label: Chemoradiotherapy(CRT)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Guosheng Wu, MD
phone: +8617857310313
phone ext: 87236858
email: guosheng_wu@zju.edu.cn
last name: Weiqin Jiang, MD
phone: +8615068117618
phone ext: 87236858
email: 1312028@zju.edu.cn
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: First Affiliated Hospital of Zhejiang University
investigator full name: Guosheng Wu
investigator title: Chief physician
mesh term: Rectal Neoplasms
sharing ipd: No