<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/NCT03840239</url>
  </required_header>
  <id_info>
    <org_study_id>2018-FXY-149</org_study_id>
    <secondary_id>5010-2018-04</secondary_id>
    <nct_id>NCT03840239</nct_id>
  </id_info>
  <brief_title>TNT to Increase the Clinical Complete Response Rate for Distal LARC</brief_title>
  <acronym>TESS</acronym>
  <official_title>Total Neoadjuvant trEatment to Increase the Clinical Complete reSponse Rate for diStal Locally Advanced Rectal Cancer (TESS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sun Yat-sen University</source>
  <oversight_info>
    <has_dmc>Yes</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 is a open-label, single-arm study to investigate the safety and efficacy of total&#xD;
      neoadjuvant treatment (TNT) in patients with locally advanced resectable rectal cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Standard treatment of rectal cancer is neoadjuvant capecitabine chemotherapy with&#xD;
      radiotherapy, followed by total mesorectal excision.&#xD;
&#xD;
      A new concept suggests organ preservation as an alternative to rectal excision in good&#xD;
      responders after neoadjuvant radiochemotherapy to decrease surgical morbidity and increase&#xD;
      quality of life.&#xD;
&#xD;
      The rational is the fact that 15%-20% of patients have sterilized tumours after&#xD;
      chemoradiotherpay for locally advanced rectal cancer. As compared to capecitabine alone,&#xD;
      oxaliplatin and more intensified chemotherapy have been shown to increase tumor regression in&#xD;
      the neoadjuvant chemoradiation setting. Meanwhile, prolong of time interval from the end of&#xD;
      radiotherapy to assessment of tumor response could further increase pathologic complete&#xD;
      response rate and complete clinical response rate.&#xD;
&#xD;
      The objective of this trial is to increase the rate of clinical complete response for distal&#xD;
      rectal cancer patients by optimizing tumour response. The investigators expect to increase&#xD;
      chance of clinical complete response by using total neoadjuvant treatment regimen as compared&#xD;
      to conventional chemoradiotherapy alone.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 25, 2018</start_date>
  <completion_date type="Anticipated">December 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 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>Rate of clinical complete response</measure>
    <time_frame>1.5 year after diagnosis</time_frame>
    <description>Rate of clinical complete response</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Ratio of sphincter preservation strategy</measure>
    <time_frame>1.5 year after diagnosis</time_frame>
    <description>Number of patients with sphincter preservation through Watch and wait strategy, or local excision, or intersphincter resection, or low anterior resection, etc.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of pathological complete response and tumor regression grade distribution</measure>
    <time_frame>1.5 year after diagnosis</time_frame>
    <description>Rate of pathological complete response and tumor regression grade distribution</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute toxicity</measure>
    <time_frame>Within the first course of anti-tumor treatment</time_frame>
    <description>Acute toxicity according to CTCAE 5.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of surgical complications</measure>
    <time_frame>1.5 year after diagnosis</time_frame>
    <description>Rate of surgical complications</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 according to Wexner Continence Grading Scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long-term toxicity grading</measure>
    <time_frame>3 year after the end of the first course of anti-tumor treatment</time_frame>
    <description>Long-term toxicity grading according to CTCAE 5.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ECOG standard score</measure>
    <time_frame>1.5 year after diagnosis</time_frame>
    <description>ECOG standard score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>3 year disease free survival</measure>
    <time_frame>3 year after the end of the first course of anti-tumor treatment</time_frame>
    <description>3 year disease free survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>5 year overall survival</measure>
    <time_frame>5 year after the end of the first course of anti-tumor treatment</time_frame>
    <description>5 year overall survival</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">98</enrollment>
  <condition>Rectal Cancer</condition>
  <condition>Rectal Cancer Stage II</condition>
  <condition>Rectal Cancer Stage III</condition>
  <condition>Chemoradiation</condition>
  <arm_group>
    <arm_group_label>TNT arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug: Neoadjuvant chemotherapy Capeox (Capecitabine + Oxaliplatin), 6 cycles; adjuvant chemotherapy, Capecitabine, 2 cycles or physicians' decision.&#xD;
External beam radiotherapy: Neoadjuvant, 50 Gy, 2 Gy/session; 25 fractions. Procedure: 'Watch and wait strategy' or surgery including local excision, intersphincter resection or total mesorectal excision or other kinds of surgeries.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine, Oxaliplatin</intervention_name>
    <description>Drug: Capecitabine, Oxaliplatin</description>
    <arm_group_label>TNT arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>External beam radiotherapy</intervention_name>
    <description>External beam radiotherapy to the primary tumor, regional lymph nodes and clinical target volume</description>
    <arm_group_label>TNT arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Surgery</intervention_name>
    <description>'Local excision' or 'Intersphincter resection' or 'Total mesorectal excision' or other surgeries</description>
    <arm_group_label>TNT arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Watch and wait strategy</intervention_name>
    <description>Watch and wait strategy recommendation and discussion for cCR patients</description>
    <arm_group_label>TNT arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Rectal adenocarcinoma&#xD;
&#xD;
          -  cT3-4aNany or cTanyN+&#xD;
&#xD;
          -  Location ≤5 cm from the anal verge&#xD;
&#xD;
          -  No distant metastasis&#xD;
&#xD;
          -  No gastrointestinal obstruction or relieved obstruction&#xD;
&#xD;
          -  No previous surgery of the rectum, no previous chemotherapy, no previous pelvic&#xD;
             radiation, no previous biotherapy&#xD;
&#xD;
          -  ECOG 0-1&#xD;
&#xD;
          -  Expected survival length ≥ 2 years&#xD;
&#xD;
          -  Age 18-70&#xD;
&#xD;
          -  Sufficient bone marrow, kidney and liver function&#xD;
&#xD;
          -  Effective contraception during the study&#xD;
&#xD;
          -  Patient and doctor have signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Distant metastasis&#xD;
&#xD;
          -  Chronic intestinal inflammation and/or bowel obstruction&#xD;
&#xD;
          -  Contra indication for chemotherapy and/or radiotherapy&#xD;
&#xD;
          -  Previous pelvic radiotherapy or chemotherapy&#xD;
&#xD;
          -  Severe renal, hepatic insufficiency (serum creatinine&lt;30ml/min)&#xD;
&#xD;
          -  Peripheral neuropathy &gt; grade 1&#xD;
&#xD;
          -  Pregnant or breast-feeding woman&#xD;
&#xD;
          -  Certain or suspicious allergy to research drug&#xD;
&#xD;
          -  Cachexia, organ dysfunction&#xD;
&#xD;
          -  Active severe infection&#xD;
&#xD;
          -  Multiple primary cancers&#xD;
&#xD;
          -  Epileptic seizures&#xD;
&#xD;
          -  Malignant history within 5 years, except cervical carcinoma in situ or cutaneous basal&#xD;
             cell carcinoma&#xD;
&#xD;
          -  Severe arrhythmia, cardiac dysfunction (NYHA grade III or IV )&#xD;
&#xD;
          -  Uncontollable severe hypertesion&#xD;
&#xD;
          -  Persons deprived of liberty or under guardianship&#xD;
&#xD;
          -  Impossibility for compliance to follow-up&#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>WeiWei Xiao</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sun Yat-sen University</affiliation>
  </overall_official>
  <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>
    <status>Recruiting</status>
    <contact>
      <last_name>WeiWei Xiao</last_name>
      <phone>8613710390520</phone>
      <phone_ext>8613710390520</phone_ext>
      <email>xiaoww@sysucc.org.cn</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>January 28, 2019</study_first_submitted>
  <study_first_submitted_qc>February 12, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <last_update_submitted>September 19, 2022</last_update_submitted>
  <last_update_submitted_qc>September 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 22, 2022</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>Associate professor</investigator_title>
  </responsible_party>
  <keyword>rectal cancer</keyword>
  <keyword>chemoradiation</keyword>
  <keyword>total neoadjuvant treatment</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>Capecitabine</mesh_term>
    <mesh_term>Oxaliplatin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03840239
org study id: 2018-FXY-149
secondary id: 5010-2018-04
nct id: NCT03840239
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a open-label, single-arm study to investigate the safety and efficacy of total
      neoadjuvant treatment (TNT) in patients with locally advanced resectable rectal cancer.
Standard treatment of rectal cancer is neoadjuvant capecitabine chemotherapy with
      radiotherapy, followed by total mesorectal excision.

      A new concept suggests organ preservation as an alternative to rectal excision in good
      responders after neoadjuvant radiochemotherapy to decrease surgical morbidity and increase
      quality of life.

      The rational is the fact that 15%-20% of patients have sterilized tumours after
      chemoradiotherpay for locally advanced rectal cancer. As compared to capecitabine alone,
      oxaliplatin and more intensified chemotherapy have been shown to increase tumor regression in
      the neoadjuvant chemoradiation setting. Meanwhile, prolong of time interval from the end of
      radiotherapy to assessment of tumor response could further increase pathologic complete
      response rate and complete clinical response rate.

      The objective of this trial is to increase the rate of clinical complete response for distal
      rectal cancer patients by optimizing tumour response. The investigators expect to increase
      chance of clinical complete response by using total neoadjuvant treatment regimen as compared
      to conventional chemoradiotherapy alone.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Rate of clinical complete response
time frame: 1.5 year after diagnosis
description: Rate of clinical complete response
measure: Ratio of sphincter preservation strategy
time frame: 1.5 year after diagnosis
description: Number of patients with sphincter preservation through Watch and wait strategy, or local excision, or intersphincter resection, or low anterior resection, etc.
measure: Rate of pathological complete response and tumor regression grade distribution
time frame: 1.5 year after diagnosis
description: Rate of pathological complete response and tumor regression grade distribution
measure: Acute toxicity
time frame: Within the first course of anti-tumor treatment
description: Acute toxicity according to CTCAE 5.0
measure: Rate of surgical complications
time frame: 1.5 year after diagnosis
description: Rate of surgical complications
measure: Long-term anal function
time frame: 1.5 year after diagnosis
description: Long-term anal function according to Wexner Continence Grading Scale
measure: Long-term toxicity grading
time frame: 3 year after the end of the first course of anti-tumor treatment
description: Long-term toxicity grading according to CTCAE 5.0
measure: ECOG standard score
time frame: 1.5 year after diagnosis
description: ECOG standard score
measure: 3 year disease free survival
time frame: 3 year after the end of the first course of anti-tumor treatment
description: 3 year disease free survival
measure: 5 year overall survival
time frame: 5 year after the end of the first course of anti-tumor treatment
description: 5 year overall survival
arm group label: TNT arm
arm group type: Experimental
description: Drug: Neoadjuvant chemotherapy Capeox (Capecitabine + Oxaliplatin), 6 cycles; adjuvant chemotherapy, Capecitabine, 2 cycles or physicians' decision.
External beam radiotherapy: Neoadjuvant, 50 Gy, 2 Gy/session; 25 fractions. Procedure: 'Watch and wait strategy' or surgery including local excision, intersphincter resection or total mesorectal excision or other kinds of surgeries.
intervention type: Drug
intervention name: Capecitabine, Oxaliplatin
description: Drug: Capecitabine, Oxaliplatin
arm group label: TNT arm
intervention type: Radiation
intervention name: External beam radiotherapy
description: External beam radiotherapy to the primary tumor, regional lymph nodes and clinical target volume
arm group label: TNT arm
intervention type: Procedure
intervention name: Surgery
description: 'Local excision' or 'Intersphincter resection' or 'Total mesorectal excision' or other surgeries
arm group label: TNT arm
intervention type: Other
intervention name: Watch and wait strategy
description: Watch and wait strategy recommendation and discussion for cCR patients
arm group label: TNT arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: WeiWei Xiao
role: Principal Investigator
affiliation: Sun Yat-sen University
last name: WeiWei Xiao
phone: 8613710390520
phone ext: 8613710390520
email: xiaoww@sysucc.org.cn
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: WeiWei Xiao
investigator title: Associate professor
mesh term: Rectal Neoplasms
mesh term: Capecitabine
mesh term: Oxaliplatin
sharing ipd: Undecided