<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/NCT03038217</url>
  </required_header>
  <id_info>
    <org_study_id>PekingUMCH-Colorectal Surgery</org_study_id>
    <nct_id>NCT03038217</nct_id>
  </id_info>
  <brief_title>Investigation of the Value of ctDNA in Diagnosis, Treatment, and Surveillance of Surgically Resectable Colorectal Cancer</brief_title>
  <official_title>Investigation of the Value of ctDNA Analysis in the Diagnosis, Treatment, and Surveillance of Patients With Surgically Resectable Colorectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking Union Medical College Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <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>
      In this study, we aim to investigate the value of circulating tumor DNA (ctDNA) analysis in&#xD;
      the diagnosis, treatment, and surveillance of patients with surgically resectable colorectal&#xD;
      cancer, by performing serial analysis of ctDNA, next-generation sequencing of surgical&#xD;
      specimens, and observation of patients undergoing radical resection of the tumor with or&#xD;
      without adjuvant chemo- and/or radiotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A prospective, observational study to determine the value of circulating tumor DNA (ctDNA)&#xD;
      for predicting the therapeutic effects of the combined modality treatment for colorectal&#xD;
      cancer and the patients' long-term prognosis.&#xD;
&#xD;
      Research objects: patients with surgically resectable colorectal cancer. After giving fully&#xD;
      informed consent, the prospective participants will undergo the classical combined modality&#xD;
      treatment according to NCCN guidelines. Serial analysis of ctDNA will be performed at&#xD;
      specific time points including pre-treatment, (post-NCRT for NCRT patients), postoperative&#xD;
      week 1, 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 3 year disease free survival&#xD;
      (3y-DFS) will be the primary end-point.&#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>Phase 3</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>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>5y DFS</measure>
    <time_frame>5 years</time_frame>
    <description>The 5-year disease free survival rate of the patients.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>5y LR</measure>
    <time_frame>5 years</time_frame>
    <description>The 5-year local recurrence rate of the patients.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>5y OS</measure>
    <time_frame>5 years</time_frame>
    <description>The 5-year overall survival rate of the patients.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes of ctDNA level after surgery</measure>
    <time_frame>1 month</time_frame>
    <description>Changes of patients' ctDNA level after undergoing surgical resection of the tumor.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes of ctDNA level after adjuvant therapy</measure>
    <time_frame>6 months</time_frame>
    <description>Changes of patients' ctDNA level after receiving adjuvant therapy (eg. adjuvant chemothearpy).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes of ctDNA level when disease recurs</measure>
    <time_frame>5 year</time_frame>
    <description>Changes of patients' ctDNA level after disease recurrence happens</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Rectal Cancer, Adenocarcinoma</condition>
  <condition>Neoadjuvant Chemoradiation</condition>
  <arm_group>
    <arm_group_label>ACT group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group of patients with pathologically confirmed Stage II-III colorectal cancer who receive postoperative treatment with chemotherapeutic agent (ACT) using Capecitabine +/- Oxaliplatin.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-ACT group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group of patients with pathologically confirmed stage II colorectal cancer who receive no adjuvant chemotherapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>LR group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group of patients with clinically staged T1-2N0 rectal cancer who undergo local resection (LR)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RR group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group of patients with clinically staged T1-2N0 rectal cancer who undergo radical resection (RR)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine +/- Oxaliplatin</intervention_name>
    <description>Patients in ACT group will undergo postoperative adjuvant chemotherapy with single agent Capecitabine regimen or combined Capecitabine +Oxaliplatin regimen.</description>
    <arm_group_label>ACT group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>local resection</intervention_name>
    <description>Patients in the LR group will undergo local resection of the T1-2N0 rectal carcinoma</description>
    <arm_group_label>LR group</arm_group_label>
    <other_name>LR</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>radical resection</intervention_name>
    <description>Patients in the RR group will undergo radical resection of the T1-2N0 rectal carcinoma</description>
    <arm_group_label>RR group</arm_group_label>
    <other_name>RR</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>No adjuvant chemotherapy</intervention_name>
    <description>Patients in Non-ACT group will not undergo postoperative adjuvant chemotherapy.</description>
    <arm_group_label>Non-ACT group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients aged 18 to 75 years old.&#xD;
&#xD;
          2. Patients with surgically resectable colorectal cancer, while without distal metastasis&#xD;
             of the disease.&#xD;
&#xD;
          3. Patients with ASA physical status scroe of I to III.&#xD;
&#xD;
          4. Patients who can fully understand the content of the informed consent form and sign it&#xD;
             upon their own opinions.&#xD;
&#xD;
          5. Patients who can coordinate with the researchers to undergo the long-term&#xD;
             post-treatment rechecks and follow-ups.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. 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&#xD;
             liver disease, pulmonary hypertension, systemic lupus erythematosis etc.).&#xD;
&#xD;
          2. Patient is pregnant or lactating.&#xD;
&#xD;
          3. Patient has a history of malignancy within 5 years except curatively treated basal&#xD;
             cell carcinoma, squamous cell carcinoma in a non-mucosal, ultraviolet exposed area, or&#xD;
             cervical carcinoma.&#xD;
&#xD;
          4. Patient is participating in any other clinical trials within 30 days prior to&#xD;
             screening.&#xD;
&#xD;
          5. Patient has severe mental illness.&#xD;
&#xD;
          6. Patient has any other conditions, which, in the opinion of the Investigator, would&#xD;
             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@yahoo.com</email>
  </overall_contact>
  <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>Stroun M, Anker P, Maurice P, Lyautey J, Lederrey C, Beljanski M. Neoplastic characteristics of the DNA found in the plasma of cancer patients. Oncology. 1989;46(5):318-22. doi: 10.1159/000226740.</citation>
    <PMID>2779946</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>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>
  <verification_date>February 2017</verification_date>
  <study_first_submitted>December 20, 2016</study_first_submitted>
  <study_first_submitted_qc>January 29, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 31, 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>neoajuvant chemoradiation</keyword>
  <keyword>circulating tumor DNA</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/NCT03038217
org study id: PekingUMCH-Colorectal Surgery
nct id: NCT03038217
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
In this study, we aim to investigate the value of circulating tumor DNA (ctDNA) analysis in
      the diagnosis, treatment, and surveillance of patients with surgically resectable colorectal
      cancer, by performing serial analysis of ctDNA, next-generation sequencing of surgical
      specimens, and observation of patients undergoing radical resection of the tumor with or
      without adjuvant chemo- and/or radiotherapy.
A prospective, observational study to determine the value of circulating tumor DNA (ctDNA)
      for predicting the therapeutic effects of the combined modality treatment for colorectal
      cancer and the patients' long-term prognosis.

      Research objects: patients with surgically resectable colorectal cancer. After giving fully
      informed consent, the prospective participants will undergo the classical combined modality
      treatment according to NCCN guidelines. Serial analysis of ctDNA will be performed at
      specific time points including pre-treatment, (post-NCRT for NCRT patients), 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 3 year disease free survival
      (3y-DFS) will be the primary end-point.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Investigator)
measure: 5y DFS
time frame: 5 years
description: The 5-year disease free survival rate of the patients.
measure: 5y LR
time frame: 5 years
description: The 5-year local recurrence rate of the patients.
measure: 5y OS
time frame: 5 years
description: The 5-year overall survival rate of the patients.
measure: Changes of ctDNA level after surgery
time frame: 1 month
description: Changes of patients' ctDNA level after undergoing surgical resection of the tumor.
measure: Changes of ctDNA level after adjuvant therapy
time frame: 6 months
description: Changes of patients' ctDNA level after receiving adjuvant therapy (eg. adjuvant chemothearpy).
measure: Changes of ctDNA level when disease recurs
time frame: 5 year
description: Changes of patients' ctDNA level after disease recurrence happens
arm group label: ACT group
arm group type: Experimental
description: Group of patients with pathologically confirmed Stage II-III colorectal cancer who receive postoperative treatment with chemotherapeutic agent (ACT) using Capecitabine +/- Oxaliplatin.
arm group label: Non-ACT group
arm group type: Experimental
description: Group of patients with pathologically confirmed stage II colorectal cancer who receive no adjuvant chemotherapy.
arm group label: LR group
arm group type: Experimental
description: Group of patients with clinically staged T1-2N0 rectal cancer who undergo local resection (LR)
arm group label: RR group
arm group type: Experimental
description: Group of patients with clinically staged T1-2N0 rectal cancer who undergo radical resection (RR)
intervention type: Drug
intervention name: Capecitabine +/- Oxaliplatin
description: Patients in ACT group will undergo postoperative adjuvant chemotherapy with single agent Capecitabine regimen or combined Capecitabine +Oxaliplatin regimen.
arm group label: ACT group
intervention type: Procedure
intervention name: local resection
description: Patients in the LR group will undergo local resection of the T1-2N0 rectal carcinoma
arm group label: LR group
other name: LR
intervention type: Procedure
intervention name: radical resection
description: Patients in the RR group will undergo radical resection of the T1-2N0 rectal carcinoma
arm group label: RR group
other name: RR
intervention type: Other
intervention name: No adjuvant chemotherapy
description: Patients in Non-ACT group will not undergo postoperative adjuvant chemotherapy.
arm group label: Non-ACT group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Jiaolin Zhou, MD
phone: 8613910136704
email: conniezhjl@yahoo.com
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.
PMID: 25654990
citation: Stroun M, Anker P, Maurice P, Lyautey J, Lederrey C, Beljanski M. Neoplastic characteristics of the DNA found in the plasma of cancer patients. Oncology. 1989;46(5):318-22. doi: 10.1159/000226740.
PMID: 2779946
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.
PMID: 27384348
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.
PMID: 27459628
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