<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/NCT04466267</url>
  </required_header>
  <id_info>
    <org_study_id>anti-EGFR-antibody</org_study_id>
    <nct_id>NCT04466267</nct_id>
  </id_info>
  <brief_title>The Molecular Mechanism of RAS Wild-type mCRC Resistance to Anti-EGFR-antibody</brief_title>
  <official_title>The Molecular Mechanism of RAS Wild-type Metastatic Colorectal Cancer (mCRC) Resistance to Anti Epidermal Growth Factor Receptor (EGFR) Antibody</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>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Establishing the genetic map of primary and secondary resistance of Chinese wild RAS&#xD;
      colorectal cancer received anti-EGFR treatment through tissues and peripheral blood NGS&#xD;
      testing. Combination genetic data with clinical characteristics, prognosis and treatment data&#xD;
      to explore the molecular mechanism of resistance of anti-EGFR-antibody.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cetuximab is a chimeric (mouse/human) monoclonal antibody, an epidermal growth factor&#xD;
      receptor (EGFR) inhibitor. Many large clinical trials demonstrated that for RAS wild-type&#xD;
      metastatic colorectal cancer (mCRC), especially left-sided RAS wild-type mCRC, cetuximab can&#xD;
      prolong OS. But some of patients have primary resistance to cetuximab and for all patients&#xD;
      received cetuximab will develop secondary resistance. Cell-free or circulating tumour DNA&#xD;
      (ctDNA) including primary site and metastatic site genetic information, which can avoid tumor&#xD;
      heterogeneity. The results of paired test detection of tissue and ctDNA showed there is 93%&#xD;
      consistency in RAS testing. Therefore, dynamic monitoring ctDNA during anti-EGFR targeted&#xD;
      treatment of RAS wild-type mCRC patients can implement prognosis of efficacy and response&#xD;
      evaluation in real-time. Besides, it can monitor the variation features of resistance gene&#xD;
      and find resistance gene in real-time. According the situation of gene change to find&#xD;
      potential drug resistance mechanism and formulate individualization treatment plan.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 1, 2017</start_date>
  <completion_date type="Actual">July 4, 2020</completion_date>
  <primary_completion_date type="Actual">March 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>The molecular mechanism of patients primary or secondary resistance to cetuximab</measure>
    <time_frame>up to 36 months</time_frame>
    <description>Dynamic monitoring ctDNA to identify potential molecular mechanism of RAS wild-type mCRC patients primary or secondary resistance to cetuximab</description>
  </primary_outcome>
  <enrollment type="Actual">40</enrollment>
  <condition>Colorectal Cancer</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Tissues and peripheral blood&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        RAS wild-type metastatic colorectal cancer patients treatment with FOLFOX/FORFIRI +&#xD;
        cetuximab&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age≥18 years, ≤75 years, all gender;&#xD;
&#xD;
          2. Histologically proven metastatic adenocarcinoma of colorectal cancer, no previous&#xD;
             history of cancer;&#xD;
&#xD;
          3. The clinical data of patient is intact;&#xD;
&#xD;
          4. The data of patients after surgery is intact, and the prognosis follow-up data of&#xD;
             patient is available.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous history of cancer；&#xD;
&#xD;
          2. Intact clinical data or diagnosis results of histopathology is unavailable;&#xD;
&#xD;
          3. Time of progression disease after treatment and follow-up data are unavailable;&#xD;
&#xD;
          4. Patient received blood transfusion within 3 months;&#xD;
&#xD;
          5. Other situation that researchers think it will impact the results of trails or violate&#xD;
             ethics.&#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>Medical Oncology,Sun Yat-sen University Cancer Center</name>
      <address>
        <city>Guanzhou</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Venook AP, Niedzwiecki D, Lenz HJ, Innocenti F, Fruth B, Meyerhardt JA, Schrag D, Greene C, O'Neil BH, Atkins JN, Berry S, Polite BN, O'Reilly EM, Goldberg RM, Hochster HS, Schilsky RL, Bertagnolli MM, El-Khoueiry AB, Watson P, Benson AB 3rd, Mulkerin DL, Mayer RJ, Blanke C. Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial. JAMA. 2017 Jun 20;317(23):2392-2401. doi: 10.1001/jama.2017.7105.</citation>
    <PMID>28632865</PMID>
  </reference>
  <reference>
    <citation>Stintzing S, Modest DP, Rossius L, Lerch MM, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran SE, Heintges T, Lerchenmuller C, Kahl C, Seipelt G, Kullmann F, Stauch M, Scheithauer W, Held S, Giessen-Jung C, Moehler M, Jagenburg A, Kirchner T, Jung A, Heinemann V; FIRE-3 investigators. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab for metastatic colorectal cancer (FIRE-3): a post-hoc analysis of tumour dynamics in the final RAS wild-type subgroup of this randomised open-label phase 3 trial. Lancet Oncol. 2016 Oct;17(10):1426-1434. doi: 10.1016/S1470-2045(16)30269-8. Epub 2016 Aug 27. Erratum In: Lancet Oncol. 2016 Oct;17 (10 ):e420. Lancet Oncol. 2016 Nov;17 (11):e479.</citation>
    <PMID>27575024</PMID>
  </reference>
  <reference>
    <citation>Tejpar S, Stintzing S, Ciardiello F, Tabernero J, Van Cutsem E, Beier F, Esser R, Lenz HJ, Heinemann V. Prognostic and Predictive Relevance of Primary Tumor Location in Patients With RAS Wild-Type Metastatic Colorectal Cancer: Retrospective Analyses of the CRYSTAL and FIRE-3 Trials. JAMA Oncol. 2017 Feb 1;3(2):194-201. doi: 10.1001/jamaoncol.2016.3797. Erratum In: JAMA Oncol. 2017 Dec 1;3(12):1742.</citation>
    <PMID>27722750</PMID>
  </reference>
  <reference>
    <citation>Batth IS, Mitra A, Manier S, Ghobrial IM, Menter D, Kopetz S, Li S. Circulating tumor markers: harmonizing the yin and yang of CTCs and ctDNA for precision medicine. Ann Oncol. 2017 Mar 1;28(3):468-477. doi: 10.1093/annonc/mdw619. Erratum In: Ann Oncol. 2019 Nov 1;30(11):1845.</citation>
    <PMID>27998963</PMID>
  </reference>
  <reference>
    <citation>Vidal J, Muinelo L, Dalmases A, Jones F, Edelstein D, Iglesias M, Orrillo M, Abalo A, Rodriguez C, Brozos E, Vidal Y, Candamio S, Vazquez F, Ruiz J, Guix M, Visa L, Sikri V, Albanell J, Bellosillo B, Lopez R, Montagut C. Plasma ctDNA RAS mutation analysis for the diagnosis and treatment monitoring of metastatic colorectal cancer patients. Ann Oncol. 2017 Jun 1;28(6):1325-1332. doi: 10.1093/annonc/mdx125.</citation>
    <PMID>28419195</PMID>
  </reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 6, 2020</study_first_submitted>
  <study_first_submitted_qc>July 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 10, 2020</study_first_posted>
  <last_update_submitted>July 6, 2020</last_update_submitted>
  <last_update_submitted_qc>July 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 10, 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>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</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/NCT04466267
org study id: anti-EGFR-antibody
nct id: NCT04466267
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Establishing the genetic map of primary and secondary resistance of Chinese wild RAS
      colorectal cancer received anti-EGFR treatment through tissues and peripheral blood NGS
      testing. Combination genetic data with clinical characteristics, prognosis and treatment data
      to explore the molecular mechanism of resistance of anti-EGFR-antibody.
Cetuximab is a chimeric (mouse/human) monoclonal antibody, an epidermal growth factor
      receptor (EGFR) inhibitor. Many large clinical trials demonstrated that for RAS wild-type
      metastatic colorectal cancer (mCRC), especially left-sided RAS wild-type mCRC, cetuximab can
      prolong OS. But some of patients have primary resistance to cetuximab and for all patients
      received cetuximab will develop secondary resistance. Cell-free or circulating tumour DNA
      (ctDNA) including primary site and metastatic site genetic information, which can avoid tumor
      heterogeneity. The results of paired test detection of tissue and ctDNA showed there is 93%
      consistency in RAS testing. Therefore, dynamic monitoring ctDNA during anti-EGFR targeted
      treatment of RAS wild-type mCRC patients can implement prognosis of efficacy and response
      evaluation in real-time. Besides, it can monitor the variation features of resistance gene
      and find resistance gene in real-time. According the situation of gene change to find
      potential drug resistance mechanism and formulate individualization treatment plan.
observational model: Cohort
time perspective: Retrospective
measure: The molecular mechanism of patients primary or secondary resistance to cetuximab
time frame: up to 36 months
description: Dynamic monitoring ctDNA to identify potential molecular mechanism of RAS wild-type mCRC patients primary or secondary resistance to cetuximab
Tissues and peripheral blood
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
citation: Venook AP, Niedzwiecki D, Lenz HJ, Innocenti F, Fruth B, Meyerhardt JA, Schrag D, Greene C, O'Neil BH, Atkins JN, Berry S, Polite BN, O'Reilly EM, Goldberg RM, Hochster HS, Schilsky RL, Bertagnolli MM, El-Khoueiry AB, Watson P, Benson AB 3rd, Mulkerin DL, Mayer RJ, Blanke C. Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial. JAMA. 2017 Jun 20;317(23):2392-2401. doi: 10.1001/jama.2017.7105.
PMID: 28632865
citation: Stintzing S, Modest DP, Rossius L, Lerch MM, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran SE, Heintges T, Lerchenmuller C, Kahl C, Seipelt G, Kullmann F, Stauch M, Scheithauer W, Held S, Giessen-Jung C, Moehler M, Jagenburg A, Kirchner T, Jung A, Heinemann V; FIRE-3 investigators. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab for metastatic colorectal cancer (FIRE-3): a post-hoc analysis of tumour dynamics in the final RAS wild-type subgroup of this randomised open-label phase 3 trial. Lancet Oncol. 2016 Oct;17(10):1426-1434. doi: 10.1016/S1470-2045(16)30269-8. Epub 2016 Aug 27. Erratum In: Lancet Oncol. 2016 Oct;17 (10 ):e420. Lancet Oncol. 2016 Nov;17 (11):e479.
PMID: 27575024
citation: Tejpar S, Stintzing S, Ciardiello F, Tabernero J, Van Cutsem E, Beier F, Esser R, Lenz HJ, Heinemann V. Prognostic and Predictive Relevance of Primary Tumor Location in Patients With RAS Wild-Type Metastatic Colorectal Cancer: Retrospective Analyses of the CRYSTAL and FIRE-3 Trials. JAMA Oncol. 2017 Feb 1;3(2):194-201. doi: 10.1001/jamaoncol.2016.3797. Erratum In: JAMA Oncol. 2017 Dec 1;3(12):1742.
PMID: 27722750
citation: Batth IS, Mitra A, Manier S, Ghobrial IM, Menter D, Kopetz S, Li S. Circulating tumor markers: harmonizing the yin and yang of CTCs and ctDNA for precision medicine. Ann Oncol. 2017 Mar 1;28(3):468-477. doi: 10.1093/annonc/mdw619. Erratum In: Ann Oncol. 2019 Nov 1;30(11):1845.
PMID: 27998963
citation: Vidal J, Muinelo L, Dalmases A, Jones F, Edelstein D, Iglesias M, Orrillo M, Abalo A, Rodriguez C, Brozos E, Vidal Y, Candamio S, Vazquez F, Ruiz J, Guix M, Visa L, Sikri V, Albanell J, Bellosillo B, Lopez R, Montagut C. Plasma ctDNA RAS mutation analysis for the diagnosis and treatment monitoring of metastatic colorectal cancer patients. Ann Oncol. 2017 Jun 1;28(6):1325-1332. doi: 10.1093/annonc/mdx125.
PMID: 28419195
responsible party type: Principal Investigator
investigator affiliation: Sun Yat-sen University
investigator full name: Ruihua Xu
investigator title: Clinical Professor
mesh term: Colorectal Neoplasms