<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/NCT04482608</url>
  </required_header>
  <id_info>
    <org_study_id>dMMR/MSI-H and chemotherapy</org_study_id>
    <nct_id>NCT04482608</nct_id>
  </id_info>
  <brief_title>The mCRC Patients With pMMR/MSS or dMMR/MSI-H Status Received Palliative Chemotherapy Efficacy and Survival</brief_title>
  <official_title>The Metastatic Colorectal Cancer Patients With Proficient Mismatch Repair (pMMR) / Microsatellite Stable (MSS) or Deficient Mismatch Repair (dMMR) / Microsatellite Instability High (MSI-H) Status Received Palliative Chemotherapy Efficacy and Survival</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Second Affiliated Hospital of Kunming Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Sun Yat-sen University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Deficient mismatch repair (dMMR) or microsatellite instability high (MSI-H) accounts for 4-5%&#xD;
      in metastatic colorectal cancer (mCRC). The efficacy and survival of patients with dMMR/MSI-H&#xD;
      status received palliative chemotherapy have not clear yet. In this study, the investigators&#xD;
      observed the efficacy and survival of dMMR/MSI-H status mCRC patients received palliative&#xD;
      first-line chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Colorectal cancer (CRC) is the one of most common cancer in the world. Loss of function of&#xD;
      DNA mismatch repair (MMR) is an important mechanism of CRC development. Mutation or&#xD;
      modification of MMR genes result in MMR protein deficient (dMMR) and microsatellite&#xD;
      instability (MSI). It has been reported that the dMMR or MSI high (MSI-H) phenotype is&#xD;
      present in approximately 15-18% of CRC patients. Most dMMR/MSI-H tumors are sporadic CRC, and&#xD;
      only approximately 3% of dMMR/MSI-H tumors are Lynch syndrome (LS) or hereditary nonpolyposis&#xD;
      colorectal carcinoma (HNPCC).&#xD;
&#xD;
      The dMMR/MSI-H status was reported to be a predictive marker for adjuvant chemotherapy.&#xD;
      Multiple retrospective studies showed that dMMR/MSI-H is correlated with a favorable&#xD;
      prognosis in stage II/III CRC. Previous studies suggested that dMMR/MSI status may be a&#xD;
      predictive marker of decreased benefit form adjuvant monotherapy of 5-fluorouracil (5-FU) in&#xD;
      patients with stage II disease, but not in those with stage III disease. For metastatic&#xD;
      colorectal cancer (mCRC), the relationship of the MMR/MSI phenotype and prognosis is unclear.&#xD;
      Some researchers found that CRC patients with the dMMR/MSI-H phenotype have a worse&#xD;
      prognosis. But other researchers thought the dMMR/MSI-H phenotype is no associate to efficacy&#xD;
      and survival of palliative chemotherapy, even is benefit for efficacy and survival.Therefore,&#xD;
      the aim of this study was to clarify whether the status of dMMR/MSI-H affected&#xD;
      progression-free survival (PFS) in mCRC patients who received first-line palliative&#xD;
      chemotherapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 1, 2019</start_date>
  <completion_date type="Actual">June 8, 2020</completion_date>
  <primary_completion_date type="Actual">April 1, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Progression-Free Survival (PFS)</measure>
    <time_frame>up to 24-36 months</time_frame>
    <description>PFS as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Response rate</measure>
    <time_frame>From first patient first visit to 6 month after last patient first visit</time_frame>
    <description>Based on Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>From first patient first visit to 6 month after last patient first visit</time_frame>
    <description>Based on Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>up to approximately 9 year</time_frame>
    <description>The time from registration to death due to any cause, or censored at date last known alive.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">671</enrollment>
  <condition>Colorectal Cancer Metastatic</condition>
  <condition>Mismatch Repair Deficiency</condition>
  <condition>Microsatellite Instability High</condition>
  <arm_group>
    <arm_group_label>pMMR/MSS mCRC patients</arm_group_label>
    <description>The metastatic colorectal cancer patients with proficient mismatch repair or microsatellite stable status.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>dMMR/MSI-H mCRC patients</arm_group_label>
    <description>The metastatic colorectal cancer patients with deficient mismatch repair or microsatellite instability high status.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        The metastatic colorectal patients with different MMR or microsatellite status received&#xD;
        palliative chemotherapy&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥ 18 years old&#xD;
&#xD;
          2. Histologically confirmed Metastatic colorectal adenocarcinoma;&#xD;
&#xD;
          3. Immunohistochemistry confirmed mismatch repair status or polymerase chain reaction&#xD;
             (pCR) / next-generation sequencing (NGS) confirmed microsatellite status&#xD;
&#xD;
          4. Received palliative chemotherapy and have complete information of treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients have not tested for mismatch repair or microsatellite&#xD;
&#xD;
          2. Patients have not received palliative chemotherapy or received palliative chemotherapy&#xD;
             but treatment information incomplete&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ying Jin, MD.,PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sun Yat-sen University</affiliation>
  </overall_official>
  <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>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 18, 2020</study_first_submitted>
  <study_first_submitted_qc>July 18, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 22, 2020</study_first_posted>
  <last_update_submitted>July 23, 2020</last_update_submitted>
  <last_update_submitted_qc>July 23, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sun Yat-sen University</investigator_affiliation>
    <investigator_full_name>Ruihua Xu</investigator_full_name>
    <investigator_title>Clinical Professor</investigator_title>
  </responsible_party>
  <keyword>Colorectal Cancer Metastatic</keyword>
  <keyword>Mismatch Repair Deficiency</keyword>
  <keyword>Microsatellite Instability High</keyword>
  <keyword>Chemotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
    <mesh_term>Microsatellite Instability</mesh_term>
  </condition_browse>
  <!-- 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/NCT04482608
org study id: dMMR/MSI-H and chemotherapy
nct id: NCT04482608
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
Deficient mismatch repair (dMMR) or microsatellite instability high (MSI-H) accounts for 4-5%
      in metastatic colorectal cancer (mCRC). The efficacy and survival of patients with dMMR/MSI-H
      status received palliative chemotherapy have not clear yet. In this study, the investigators
      observed the efficacy and survival of dMMR/MSI-H status mCRC patients received palliative
      first-line chemotherapy.
Colorectal cancer (CRC) is the one of most common cancer in the world. Loss of function of
      DNA mismatch repair (MMR) is an important mechanism of CRC development. Mutation or
      modification of MMR genes result in MMR protein deficient (dMMR) and microsatellite
      instability (MSI). It has been reported that the dMMR or MSI high (MSI-H) phenotype is
      present in approximately 15-18% of CRC patients. Most dMMR/MSI-H tumors are sporadic CRC, and
      only approximately 3% of dMMR/MSI-H tumors are Lynch syndrome (LS) or hereditary nonpolyposis
      colorectal carcinoma (HNPCC).

      The dMMR/MSI-H status was reported to be a predictive marker for adjuvant chemotherapy.
      Multiple retrospective studies showed that dMMR/MSI-H is correlated with a favorable
      prognosis in stage II/III CRC. Previous studies suggested that dMMR/MSI status may be a
      predictive marker of decreased benefit form adjuvant monotherapy of 5-fluorouracil (5-FU) in
      patients with stage II disease, but not in those with stage III disease. For metastatic
      colorectal cancer (mCRC), the relationship of the MMR/MSI phenotype and prognosis is unclear.
      Some researchers found that CRC patients with the dMMR/MSI-H phenotype have a worse
      prognosis. But other researchers thought the dMMR/MSI-H phenotype is no associate to efficacy
      and survival of palliative chemotherapy, even is benefit for efficacy and survival.Therefore,
      the aim of this study was to clarify whether the status of dMMR/MSI-H affected
      progression-free survival (PFS) in mCRC patients who received first-line palliative
      chemotherapy.
observational model: Cohort
time perspective: Retrospective
measure: Progression-Free Survival (PFS)
time frame: up to 24-36 months
description: PFS as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1
measure: Response rate
time frame: From first patient first visit to 6 month after last patient first visit
description: Based on Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)
measure: Disease Control Rate (DCR)
time frame: From first patient first visit to 6 month after last patient first visit
description: Based on Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)
measure: Overall survival
time frame: up to approximately 9 year
description: The time from registration to death due to any cause, or censored at date last known alive.
arm group label: pMMR/MSS mCRC patients
description: The metastatic colorectal cancer patients with proficient mismatch repair or microsatellite stable status.
arm group label: dMMR/MSI-H mCRC patients
description: The metastatic colorectal cancer patients with deficient mismatch repair or microsatellite instability high status.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Ying Jin, MD.,PhD
role: Principal Investigator
affiliation: Sun Yat-sen University
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Ruihua Xu
investigator title: Clinical Professor
mesh term: Colorectal Neoplasms
mesh term: Microsatellite Instability