<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/NCT03042000</url>
  </required_header>
  <id_info>
    <org_study_id>PUMCH-Colorectal Surgery 02</org_study_id>
    <nct_id>NCT03042000</nct_id>
  </id_info>
  <brief_title>Multicenter, Prospective, RCT：Investigation of Combined Modality Therapy for Locally Advanced Mid/Low Rectal Cancer.</brief_title>
  <official_title>A Multicenter, Prospective, Randomized Clinical Trial to Investigate the Combined Modality Therapy for Locally Advanced Mid/Low Rectal Cancer.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking Union Medical College Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Beijing Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Beijing Chao Yang Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Peking University People's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Peking University Cancer Hospital &amp; Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Beijing Friendship Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Geneplus-Beijing Co. Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Peking Union Medical College Hospital</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>
      At present, the combined modality treatment of preoperative neoadjuvant chemoradiotherapy&#xD;
      (NCRT) followed by radical surgery has become the standard of care for the locally advanced&#xD;
      mid/low rectal cancer, having been proved to substantially improve the local control of the&#xD;
      disease, whereas not being able to improve the long-term survival. According to present&#xD;
      clinical practice guidelines, all patients with cT3-4N0M0 or cTanyN1-2M0 mid/low rectal&#xD;
      cancer are recommended to undergo the preoperative long-term radiotherapy with concurrent 5FU&#xD;
      based chemotherapy, followed by the radical resection of the tumor. After surgery, adjuvant&#xD;
      chemotherapy (ACT) is recommended for all these patients without considering the&#xD;
      postoperative pathological results. Recently, however, some authors proposed that different&#xD;
      strategy of combined modality therapy should be applied in different patients according to&#xD;
      their risk of relapse, instead of using the uniform NCRT strategy. In this research, on the&#xD;
      basis of investigator's previous clinical practice and researches, investigators plan to&#xD;
      stratify the patients with cT3-4N0M0 or cTanyN1-2M0 mid/low rectal cancer into several&#xD;
      subgroups according to tumor stages and the risk of relapse. Different therapeutic strategy&#xD;
      will be applied in different groups, at the aim of improving the overall therapeutic effects,&#xD;
      as well as reducing the treatment adverse effects.&#xD;
&#xD;
      This research consists of four trials.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Trial A: A multicenter, prospective, randomized trial to compare neoadjuvant&#xD;
      chemoradiotherapy (NCRT) followed by radical surgery with surgery alone for cT3a-bN0-1aM0 mid&#xD;
      rectal cancer.&#xD;
&#xD;
      Research objects: Patients with locally advanced rectal cancer, being clinically staged&#xD;
      T3a-bN0-1aM0 by rectal MRI and/or endorectal ultrasonography (ERUS), the tumor being located&#xD;
      6-12 cm above the anal verge.&#xD;
&#xD;
      After giving fully informed consent, the prospective participants will be randomly divided&#xD;
      into two groups, receiving the following two treatment modalities.&#xD;
&#xD;
      Group A1: radical surgery + adjuvant chemotherapy (ACT) Group A2: NCRT + radical surgery +&#xD;
      ACT&#xD;
&#xD;
      Trial B: A multicenter, prospective, randomized trial to compare combined versus single-agent&#xD;
      chemotherapy with concurrent radiotherapy for cT4NanyM0 or cTanyN2M0 rectal cancer.&#xD;
&#xD;
      Research objects: Patients with locally advanced rectal cancer, being clinically staged&#xD;
      cT4NanyM0 or cTanyN2M0 by rectal MRI and/or ERUS, or patients with any other risk factors for&#xD;
      tumor relapse.&#xD;
&#xD;
      After giving fully informed consent, the prospective participants will be randomly divided&#xD;
      into two groups, receiving the following two treatment modalities.&#xD;
&#xD;
      Group A1: NCRT with combined chemotherapy (Capox regimen) + radical surgery + ACT Group A2:&#xD;
      NCRT with single-agent chemotherapy (Capecitabine) + radical surgery + ACT&#xD;
&#xD;
      Trial C: A multicenter, prospective, randomized trial to compare transanal ndoscopic&#xD;
      microsurgery (TEM) excision versus radical resection of rectal cancer being staged clinical&#xD;
      complete response (cCR) after NCRT.&#xD;
&#xD;
      Research objects: Patients with locally advanced rectal cancer, being clinically staged cCR&#xD;
      after NCRT.&#xD;
&#xD;
      After giving fully informed consent, the prospective participants will be randomly divided&#xD;
      into two groups, receiving the following two treatment modalities.&#xD;
&#xD;
      Group A1: TEM excision + ACT Group A2: radical surgery + ACT&#xD;
&#xD;
      Trial D: A prospective, observational study to determine the value of circulating tumor DNA&#xD;
      (ctDNA) for predicting the therapeutic effects of NCRT for locally advanced rectal cancer and&#xD;
      the patients' long-term prognosis.&#xD;
&#xD;
      Research objects: Patients with locally advanced mid/low rectal cancer (cT3-4N0M0 or&#xD;
      cTanyN+M0) who undergo NCRT.&#xD;
&#xD;
      After giving fully informed consent, the prospective participants will undergo the classical&#xD;
      'NCRT + radical surgery + ACT' comprehensive treatment. Serial analysis of ctDNA will be&#xD;
      performed at specific time points including pre-NCRT, post-NCRT, postoperative week 1,&#xD;
      post-ACT, postoperative year 1, 2, and 3. The next-generation sequencing of surgical&#xD;
      specimens will be performed as well. Participants will be observed and examined during the&#xD;
      entire course of treatment and the follow-up period. The pathological results of the surgical&#xD;
      specimen and the 3 year disease free survival (3y-DFS) will be the main end-points.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">February 2017</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">December 2020</primary_completion_date>
  <phase>N/A</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>3y-DFS</measure>
    <time_frame>3 years</time_frame>
    <description>the 3-year disease free survival rate</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>3y-OS</measure>
    <time_frame>3 years</time_frame>
    <description>the 3-year overall survival rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>5y-DFS</measure>
    <time_frame>5 years</time_frame>
    <description>the 5-year disease free survival rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>5y-OS</measure>
    <time_frame>5 years</time_frame>
    <description>the 5-year overall survival rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>pCR</measure>
    <time_frame>4 months</time_frame>
    <description>pathological complete tumor response rate</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Anticipated">1200</enrollment>
  <condition>Rectal Cancer, Adenocarcinoma</condition>
  <condition>Neoadjuvant Chemoradiation</condition>
  <arm_group>
    <arm_group_label>Group A1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with cT3a-bN0-1aM0 mid rectal cancer who undergo the treatment modality of 'radical surgery + adjuvant chemotherapy (ACT)'</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group A2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients with cT3a-bN0-1aM0 mid rectal cancer who undergo the treatment modality of 'NCRT + radical surgery + ACT'</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with cT4NanyM0 or cTanyN2M0 mid/low rectal cancer who undergo the treatment modality of 'NCRT with combined chemotherapy (Capox regimen) + radical surgery + ACT'</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients with cT4NanyM0 or cTanyN2M0 mid/low rectal cancer who undergo the treatment modality of 'NCRT with single-agent chemotherapy (Capecitabine) + radical surgery + ACT'</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group C1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with locally advanced rectal cancer, being clinically staged cCR after NCRT, who undergo the transanal endoscopic microsurgery (TEM) excision of the lesion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group C2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients with locally advanced rectal cancer, being clinically staged cCR after NCRT, who undergo the radical resection of the lesion.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>non-NCRT</intervention_name>
    <description>without the preoperative concurrent chemoradiothearpy (no neoadjuvant chemoradiation)</description>
    <arm_group_label>Group A1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>NCRT</intervention_name>
    <description>the preoperative concurrent chemoradiothearpy (neoadjuvant chemoradiation)</description>
    <arm_group_label>Group A2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>capecitabine with oxaliplatin</intervention_name>
    <description>combined chemotherapy with capecitabine with oxaliplatin</description>
    <arm_group_label>Group B1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>capecitabine</intervention_name>
    <description>single-agent chemotherapy with capecitabine</description>
    <arm_group_label>Group B2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>TEM</intervention_name>
    <description>transanal endoscopic microsurgery (TEM) excision of the lesion</description>
    <arm_group_label>Group C1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>radical resection</intervention_name>
    <description>radical resection of rectal cancer</description>
    <arm_group_label>Group C2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients aged 18 to 75 years old. Patients with cT3-4N0M0 or cTanyN+M0 mid/low rectal&#xD;
        cancer. Patients with ASA physical status scroe of I to III. Patients who can fully&#xD;
        understand the content of the informed consent form and sign it upon their own opinions.&#xD;
&#xD;
        Patients who can coordinate with the researchers to undergo the long-term post-treatment&#xD;
        rechecks and follow-ups.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patient has any underlying or current medical condition, which, in the opinion of the&#xD;
        Investigator, would interfere with the evaluation of the patient (e.g., end-stage liver&#xD;
        disease, pulmonary hypertension, systemic lupus erythematosis etc.).&#xD;
&#xD;
        Patient is pregnant or lactating. Patient has a history of malignancy within 5 years except&#xD;
        curatively treated basal cell carcinoma, squamous cell carcinoma in a non-mucosal,&#xD;
        ultraviolet exposed area, or cervical carcinoma.&#xD;
&#xD;
        Patient is participating in any other clinical trials within 30 days prior to screening.&#xD;
&#xD;
        Patient has severe mental illness. Patient has any other conditions, which, in the opinion&#xD;
        of the Investigator, would interfere with the evaluation of the subject.&#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>Jiaolin Zhou, MD.</last_name>
    <phone>8613910136704</phone>
    <email>conniezhjl@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Guole Lin, MD.</last_name>
    <phone>861069152211</phone>
    <email>linglpumch@163.com</email>
  </overall_contact_backup>
  <reference>
    <citation>Zhou J, Qiu H, Lin G, Xiao Y, Wu B, Wu W, Sun X, Lu J, Zhang G, Xu L, Liu Y. Is adjuvant chemotherapy necessary for patients with pathological complete response after neoadjuvant chemoradiotherapy and radical surgery in locally advanced rectal cancer? Long-term analysis of 40 ypCR patients at a single center. Int J Colorectal Dis. 2016 Jun;31(6):1163-8. doi: 10.1007/s00384-016-2579-5. Epub 2016 Apr 5.</citation>
    <PMID>27044403</PMID>
  </reference>
  <reference>
    <citation>Ferrari L, Fichera A. Neoadjuvant chemoradiation therapy and pathological complete response in rectal cancer. Gastroenterol Rep (Oxf). 2015 Nov;3(4):277-88. doi: 10.1093/gastro/gov039. Epub 2015 Aug 19.</citation>
    <PMID>26290512</PMID>
  </reference>
  <reference>
    <citation>Breugom AJ, Swets M, Bosset JF, Collette L, Sainato A, Cionini L, Glynne-Jones R, Counsell N, Bastiaannet E, van den Broek CB, Liefers GJ, Putter H, van de Velde CJ. Adjuvant chemotherapy after preoperative (chemo)radiotherapy and surgery for patients with rectal cancer: a systematic review and meta-analysis of individual patient data. Lancet Oncol. 2015 Feb;16(2):200-7. doi: 10.1016/S1470-2045(14)71199-4. Epub 2015 Jan 12.</citation>
    <PMID>25589192</PMID>
  </reference>
  <reference>
    <citation>Bosset JF, Calais G, Mineur L, Maingon P, Stojanovic-Rundic S, Bensadoun RJ, Bardet E, Beny A, Ollier JC, Bolla M, Marchal D, Van Laethem JL, Klein V, Giralt J, Clavere P, Glanzmann C, Cellier P, Collette L; EORTC Radiation Oncology Group. Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study. Lancet Oncol. 2014 Feb;15(2):184-90. doi: 10.1016/S1470-2045(13)70599-0. Epub 2014 Jan 17.</citation>
    <PMID>24440473</PMID>
  </reference>
  <reference>
    <citation>Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr, Kinzler KW. Cancer genome landscapes. Science. 2013 Mar 29;339(6127):1546-58. doi: 10.1126/science.1235122.</citation>
    <PMID>23539594</PMID>
  </reference>
  <reference>
    <citation>Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, Bartlett BR, Wang H, Luber B, Alani RM, Antonarakis ES, Azad NS, Bardelli A, Brem H, Cameron JL, Lee CC, Fecher LA, Gallia GL, Gibbs P, Le D, Giuntoli RL, Goggins M, Hogarty MD, Holdhoff M, Hong SM, Jiao Y, Juhl HH, Kim JJ, Siravegna G, Laheru DA, Lauricella C, Lim M, Lipson EJ, Marie SK, Netto GJ, Oliner KS, Olivi A, Olsson L, Riggins GJ, Sartore-Bianchi A, Schmidt K, Shih lM, Oba-Shinjo SM, Siena S, Theodorescu D, Tie J, Harkins TT, Veronese S, Wang TL, Weingart JD, Wolfgang CL, Wood LD, Xing D, Hruban RH, Wu J, Allen PJ, Schmidt CM, Choti MA, Velculescu VE, Kinzler KW, Vogelstein B, Papadopoulos N, Diaz LA Jr. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014 Feb 19;6(224):224ra24. doi: 10.1126/scitranslmed.3007094.</citation>
    <PMID>24553385</PMID>
  </reference>
  <reference>
    <citation>Dawson SJ, Tsui DW, Murtaza M, Biggs H, Rueda OM, Chin SF, Dunning MJ, Gale D, Forshew T, Mahler-Araujo B, Rajan S, Humphray S, Becq J, Halsall D, Wallis M, Bentley D, Caldas C, Rosenfeld N. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med. 2013 Mar 28;368(13):1199-209. doi: 10.1056/NEJMoa1213261. Epub 2013 Mar 13.</citation>
    <PMID>23484797</PMID>
  </reference>
  <reference>
    <citation>Zhou J, Chang L, Guan Y, Yang L, Xia X, Cui L, Yi X, Lin G. Application of Circulating Tumor DNA as a Non-Invasive Tool for Monitoring the Progression of Colorectal Cancer. PLoS One. 2016 Jul 26;11(7):e0159708. doi: 10.1371/journal.pone.0159708. eCollection 2016.</citation>
    <PMID>27459628</PMID>
  </reference>
  <reference>
    <citation>Reinert T, Scholer LV, Thomsen R, Tobiasen H, Vang S, Nordentoft I, Lamy P, Kannerup AS, Mortensen FV, Stribolt K, Hamilton-Dutoit S, Nielsen HJ, Laurberg S, Pallisgaard N, Pedersen JS, Orntoft TF, Andersen CL. Analysis of circulating tumour DNA to monitor disease burden following colorectal cancer surgery. Gut. 2016 Apr;65(4):625-34. doi: 10.1136/gutjnl-2014-308859. Epub 2015 Feb 4.</citation>
    <PMID>25654990</PMID>
  </reference>
  <reference>
    <citation>Tie J, Wang Y, Tomasetti C, Li L, Springer S, Kinde I, Silliman N, Tacey M, Wong HL, Christie M, Kosmider S, Skinner I, Wong R, Steel M, Tran B, Desai J, Jones I, Haydon A, Hayes T, Price TJ, Strausberg RL, Diaz LA Jr, Papadopoulos N, Kinzler KW, Vogelstein B, Gibbs P. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med. 2016 Jul 6;8(346):346ra92. doi: 10.1126/scitranslmed.aaf6219.</citation>
    <PMID>27384348</PMID>
  </reference>
  <reference>
    <citation>Jung KU, Kim HC, Park JO, Park YS, Park HC, Choi DH, Cho YB, Yun SH, Lee WY, Chun HK. Adjuvant chemotherapy after neoadjuvant chemoradiation and curative resection for rectal cancer: is it necessary for all patients? J Surg Oncol. 2015 Mar 15;111(4):439-44. doi: 10.1002/jso.23835. Epub 2014 Dec 9.</citation>
    <PMID>25488390</PMID>
  </reference>
  <verification_date>February 2017</verification_date>
  <study_first_submitted>February 2, 2017</study_first_submitted>
  <study_first_submitted_qc>February 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 3, 2017</study_first_posted>
  <last_update_submitted>February 2, 2017</last_update_submitted>
  <last_update_submitted_qc>February 2, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 3, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Peking Union Medical College Hospital</investigator_affiliation>
    <investigator_full_name>Guole Lin</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>rectal cancer</keyword>
  <keyword>neoadjuvant chemoradiation</keyword>
  <keyword>circulating tumor DNA</keyword>
  <keyword>local recurrence</keyword>
  <keyword>long-term survival</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/NCT03042000
org study id: PUMCH-Colorectal Surgery 02
nct id: NCT03042000
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
At present, the combined modality treatment of preoperative neoadjuvant chemoradiotherapy
      (NCRT) followed by radical surgery has become the standard of care for the locally advanced
      mid/low rectal cancer, having been proved to substantially improve the local control of the
      disease, whereas not being able to improve the long-term survival. According to present
      clinical practice guidelines, all patients with cT3-4N0M0 or cTanyN1-2M0 mid/low rectal
      cancer are recommended to undergo the preoperative long-term radiotherapy with concurrent 5FU
      based chemotherapy, followed by the radical resection of the tumor. After surgery, adjuvant
      chemotherapy (ACT) is recommended for all these patients without considering the
      postoperative pathological results. Recently, however, some authors proposed that different
      strategy of combined modality therapy should be applied in different patients according to
      their risk of relapse, instead of using the uniform NCRT strategy. In this research, on the
      basis of investigator's previous clinical practice and researches, investigators plan to
      stratify the patients with cT3-4N0M0 or cTanyN1-2M0 mid/low rectal cancer into several
      subgroups according to tumor stages and the risk of relapse. Different therapeutic strategy
      will be applied in different groups, at the aim of improving the overall therapeutic effects,
      as well as reducing the treatment adverse effects.

      This research consists of four trials.
Trial A: A multicenter, prospective, randomized trial to compare neoadjuvant
      chemoradiotherapy (NCRT) followed by radical surgery with surgery alone for cT3a-bN0-1aM0 mid
      rectal cancer.

      Research objects: Patients with locally advanced rectal cancer, being clinically staged
      T3a-bN0-1aM0 by rectal MRI and/or endorectal ultrasonography (ERUS), the tumor being located
      6-12 cm above the anal verge.

      After giving fully informed consent, the prospective participants will be randomly divided
      into two groups, receiving the following two treatment modalities.

      Group A1: radical surgery + adjuvant chemotherapy (ACT) Group A2: NCRT + radical surgery +
      ACT

      Trial B: A multicenter, prospective, randomized trial to compare combined versus single-agent
      chemotherapy with concurrent radiotherapy for cT4NanyM0 or cTanyN2M0 rectal cancer.

      Research objects: Patients with locally advanced rectal cancer, being clinically staged
      cT4NanyM0 or cTanyN2M0 by rectal MRI and/or ERUS, or patients with any other risk factors for
      tumor relapse.

      After giving fully informed consent, the prospective participants will be randomly divided
      into two groups, receiving the following two treatment modalities.

      Group A1: NCRT with combined chemotherapy (Capox regimen) + radical surgery + ACT Group A2:
      NCRT with single-agent chemotherapy (Capecitabine) + radical surgery + ACT

      Trial C: A multicenter, prospective, randomized trial to compare transanal ndoscopic
      microsurgery (TEM) excision versus radical resection of rectal cancer being staged clinical
      complete response (cCR) after NCRT.

      Research objects: Patients with locally advanced rectal cancer, being clinically staged cCR
      after NCRT.

      After giving fully informed consent, the prospective participants will be randomly divided
      into two groups, receiving the following two treatment modalities.

      Group A1: TEM excision + ACT Group A2: radical surgery + ACT

      Trial D: A prospective, observational study to determine the value of circulating tumor DNA
      (ctDNA) for predicting the therapeutic effects of NCRT for locally advanced rectal cancer and
      the patients' long-term prognosis.

      Research objects: Patients with locally advanced mid/low rectal cancer (cT3-4N0M0 or
      cTanyN+M0) who undergo NCRT.

      After giving fully informed consent, the prospective participants will undergo the classical
      'NCRT + radical surgery + ACT' comprehensive treatment. Serial analysis of ctDNA will be
      performed at specific time points including pre-NCRT, post-NCRT, postoperative week 1,
      post-ACT, postoperative year 1, 2, and 3. The next-generation sequencing of surgical
      specimens will be performed as well. Participants will be observed and examined during the
      entire course of treatment and the follow-up period. The pathological results of the surgical
      specimen and the 3 year disease free survival (3y-DFS) will be the main end-points.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: 3y-DFS
time frame: 3 years
description: the 3-year disease free survival rate
measure: 3y-OS
time frame: 3 years
description: the 3-year overall survival rate
measure: 5y-DFS
time frame: 5 years
description: the 5-year disease free survival rate
measure: 5y-OS
time frame: 5 years
description: the 5-year overall survival rate
measure: pCR
time frame: 4 months
description: pathological complete tumor response rate
arm group label: Group A1
arm group type: Experimental
description: Patients with cT3a-bN0-1aM0 mid rectal cancer who undergo the treatment modality of 'radical surgery + adjuvant chemotherapy (ACT)'
arm group label: Group A2
arm group type: Active Comparator
description: Patients with cT3a-bN0-1aM0 mid rectal cancer who undergo the treatment modality of 'NCRT + radical surgery + ACT'
arm group label: Group B1
arm group type: Experimental
description: Patients with cT4NanyM0 or cTanyN2M0 mid/low rectal cancer who undergo the treatment modality of 'NCRT with combined chemotherapy (Capox regimen) + radical surgery + ACT'
arm group label: Group B2
arm group type: Active Comparator
description: Patients with cT4NanyM0 or cTanyN2M0 mid/low rectal cancer who undergo the treatment modality of 'NCRT with single-agent chemotherapy (Capecitabine) + radical surgery + ACT'
arm group label: Group C1
arm group type: Experimental
description: Patients with locally advanced rectal cancer, being clinically staged cCR after NCRT, who undergo the transanal endoscopic microsurgery (TEM) excision of the lesion.
arm group label: Group C2
arm group type: Active Comparator
description: Patients with locally advanced rectal cancer, being clinically staged cCR after NCRT, who undergo the radical resection of the lesion.
intervention type: Other
intervention name: non-NCRT
description: without the preoperative concurrent chemoradiothearpy (no neoadjuvant chemoradiation)
arm group label: Group A1
intervention type: Other
intervention name: NCRT
description: the preoperative concurrent chemoradiothearpy (neoadjuvant chemoradiation)
arm group label: Group A2
intervention type: Drug
intervention name: capecitabine with oxaliplatin
description: combined chemotherapy with capecitabine with oxaliplatin
arm group label: Group B1
intervention type: Drug
intervention name: capecitabine
description: single-agent chemotherapy with capecitabine
arm group label: Group B2
intervention type: Procedure
intervention name: TEM
description: transanal endoscopic microsurgery (TEM) excision of the lesion
arm group label: Group C1
intervention type: Procedure
intervention name: radical resection
description: radical resection of rectal cancer
arm group label: Group C2
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Jiaolin Zhou, MD.
phone: 8613910136704
email: conniezhjl@163.com
last name: Guole Lin, MD.
phone: 861069152211
email: linglpumch@163.com
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PMID: 27044403
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PMID: 25488390
responsible party type: Principal Investigator
investigator affiliation: Peking Union Medical College Hospital
investigator full name: Guole Lin
investigator title: Professor
mesh term: Rectal Neoplasms
mesh term: Capecitabine
mesh term: Oxaliplatin
sharing ipd: Undecided