<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/NCT03030508</url>
  </required_header>
  <id_info>
    <org_study_id>WChen</org_study_id>
    <nct_id>NCT03030508</nct_id>
  </id_info>
  <brief_title>Discovery and Validate of Multi-genetic Biomarkers for Capecitabine in Chinese Colorectal Patients</brief_title>
  <official_title>Discovery and Validate of Multi-genetic Biomarkers for Capecitabine in Chinese Colorectal Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Changzheng Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Xinhua Hospital, Shanghai Jiao Tong University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shanghai Minhang Central Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Xuzhou Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The 97 Hospital of chinese PLA</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Changhai Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Shanghai Changzheng 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, chemotherapy is widely used in the adjuvant treatment of colorectal cancer&#xD;
      patients after surgery. Capecitabine is one of the main chemotherapeutic drugs. But the&#xD;
      effect is not good enough, the adverse reaction is serious, and the individual differences&#xD;
      were significant. The present study shows that these problems are related to the differences&#xD;
      in the exposure of capecitabine and its metabolites in different patients. The genetic&#xD;
      biomarkers for capecitabine include DRD, MTHFR and TYMS. Mutations in these genes directly&#xD;
      affect the expression of metabolic enzymes involved in capecitabine and control the&#xD;
      concentration of capecitabine and its metabolites. However, these markers have been obtained&#xD;
      through clinical trials in the United States, and their role in predicting the effectiveness&#xD;
      or safety of capecitabine and its metabolites has not been validated in Chinese cancer&#xD;
      patients.The study was based on a case study of patients with colorectal cancer in China, and&#xD;
      capecitabine as the primary postoperative chemotherapy regimen to verify whether the&#xD;
      available biomarkers can be used to predict the effectiveness and safety of capecitabine. To&#xD;
      clarify the effect of capecitabine on endogenous metabolites, and to study the mechanism of&#xD;
      its effect, so as to discover new biomarkers.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Enrolling by invitation</last_known_status>
  <start_date>January 2016</start_date>
  <completion_date type="Anticipated">March 2019</completion_date>
  <primary_completion_date type="Anticipated">January 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>during chemotherapy</time_frame>
    <description>Adverse Events That Are Related to Treatment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Disease-free survival</measure>
    <time_frame>Three year disease-free survival</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Three year disease free survival rate</measure>
    <time_frame>Three year disease free survival rate</time_frame>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Colorectal Cancer</condition>
  <condition>Capecitabine</condition>
  <arm_group>
    <arm_group_label>Group cap</arm_group_label>
    <description>Patients receiving capecitabine chemotherapy after operation</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>No intervention</intervention_name>
    <arm_group_label>Group cap</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      tissue,blood,urine and stool sample&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        300 patients with colorectal cancer receiving first chemotherapy after surgery&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. more than 18 years old;&#xD;
&#xD;
          2. patients with colon cancer diagnosed by biopsy (regardless of cancer stage);&#xD;
&#xD;
          3. received postoperative containing capecitabine chemotherapy;&#xD;
&#xD;
          4. volunteer to participate in the experiment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. pregnant and lactating women;&#xD;
&#xD;
          2. patients with hypersensitivity to fluorouracil or severe metabolic failure;&#xD;
&#xD;
          3. patients with severe infection;&#xD;
&#xD;
          4. patients with other cancers other than colorectal cancer within the first five years&#xD;
             of colorectal cancer surgery;&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wansheng Chen, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Department of medicine of Shanghai Changzheng Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of medicine of Shanghai Changzheng Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200003</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Zhang X, Sun B, Lu Z. Evaluation of clinical value of single nucleotide polymorphisms of dihydropyrimidine dehydrogenase gene to predict 5-fluorouracil toxicity in 60 colorectal cancer patients in China. Int J Med Sci. 2013 May 20;10(7):894-902. doi: 10.7150/ijms.5556. Print 2013.</citation>
    <PMID>23781135</PMID>
  </reference>
  <reference>
    <citation>Li F, Qin X, Chen H, Qiu L, Guo Y, Liu H, Chen G, Song G, Wang X, Li F, Guo S, Wang B, Li Z. Lipid profiling for early diagnosis and progression of colorectal cancer using direct-infusion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. Rapid Commun Mass Spectrom. 2013 Jan 15;27(1):24-34. doi: 10.1002/rcm.6420.</citation>
    <PMID>23239314</PMID>
  </reference>
  <reference>
    <citation>Ikeda K, Oike Y, Shimizu T, Taguchi R. Global analysis of triacylglycerols including oxidized molecular species by reverse-phase high resolution LC/ESI-QTOF MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Sep 1;877(25):2639-47. doi: 10.1016/j.jchromb.2009.03.047. Epub 2009 Apr 7.</citation>
    <PMID>19481987</PMID>
  </reference>
  <reference>
    <citation>Denkert C, Bucher E, Hilvo M, Salek R, Oresic M, Griffin J, Brockmoller S, Klauschen F, Loibl S, Barupal DK, Budczies J, Iljin K, Nekljudova V, Fiehn O. Metabolomics of human breast cancer: new approaches for tumor typing and biomarker discovery. Genome Med. 2012 Apr 30;4(4):37. doi: 10.1186/gm336.</citation>
    <PMID>22546809</PMID>
  </reference>
  <reference>
    <citation>Wu CW, Ng SS, Dong YJ, Ng SC, Leung WW, Lee CW, Wong YN, Chan FK, Yu J, Sung JJ. Detection of miR-92a and miR-21 in stool samples as potential screening biomarkers for colorectal cancer and polyps. Gut. 2012 May;61(5):739-45. doi: 10.1136/gut.2011.239236. Epub 2011 Sep 19.</citation>
    <PMID>21930727</PMID>
  </reference>
  <reference>
    <citation>Deenen MJ, Meulendijks D, Cats A, Sechterberger MK, Severens JL, Boot H, Smits PH, Rosing H, Mandigers CM, Soesan M, Beijnen JH, Schellens JH. Upfront Genotyping of DPYD*2A to Individualize Fluoropyrimidine Therapy: A Safety and Cost Analysis. J Clin Oncol. 2016 Jan 20;34(3):227-34. doi: 10.1200/JCO.2015.63.1325. Epub 2015 Nov 16.</citation>
    <PMID>26573078</PMID>
  </reference>
  <reference>
    <citation>Huang L, Chen F, Chen Y, Yang X, Xu S, Ge S, Fu S, Chao T, Yu Q, Liao X, Hu G, Zhang P, Yuan X. Thymidine phosphorylase gene variant, platelet counts and survival in gastrointestinal cancer patients treated by fluoropyrimidines. Sci Rep. 2014 Jul 16;4:5697. doi: 10.1038/srep05697.</citation>
    <PMID>25027354</PMID>
  </reference>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>January 13, 2017</study_first_submitted>
  <study_first_submitted_qc>January 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 25, 2017</study_first_posted>
  <last_update_submitted>January 22, 2017</last_update_submitted>
  <last_update_submitted_qc>January 22, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 25, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shanghai Changzheng Hospital</investigator_affiliation>
    <investigator_full_name>Wansheng Chen</investigator_full_name>
    <investigator_title>Professor, Director of Department of Pharmacy</investigator_title>
  </responsible_party>
  <keyword>biomarks</keyword>
  <keyword>colorectal cancer</keyword>
  <keyword>capecitabine</keyword>
  <keyword>gene polymorphism</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03030508
org study id: WChen
nct id: NCT03030508
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
At present, chemotherapy is widely used in the adjuvant treatment of colorectal cancer
      patients after surgery. Capecitabine is one of the main chemotherapeutic drugs. But the
      effect is not good enough, the adverse reaction is serious, and the individual differences
      were significant. The present study shows that these problems are related to the differences
      in the exposure of capecitabine and its metabolites in different patients. The genetic
      biomarkers for capecitabine include DRD, MTHFR and TYMS. Mutations in these genes directly
      affect the expression of metabolic enzymes involved in capecitabine and control the
      concentration of capecitabine and its metabolites. However, these markers have been obtained
      through clinical trials in the United States, and their role in predicting the effectiveness
      or safety of capecitabine and its metabolites has not been validated in Chinese cancer
      patients.The study was based on a case study of patients with colorectal cancer in China, and
      capecitabine as the primary postoperative chemotherapy regimen to verify whether the
      available biomarkers can be used to predict the effectiveness and safety of capecitabine. To
      clarify the effect of capecitabine on endogenous metabolites, and to study the mechanism of
      its effect, so as to discover new biomarkers.
observational model: Case-Control
time perspective: Prospective
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
time frame: during chemotherapy
description: Adverse Events That Are Related to Treatment
measure: Disease-free survival
time frame: Three year disease-free survival
measure: Three year disease free survival rate
time frame: Three year disease free survival rate
arm group label: Group cap
description: Patients receiving capecitabine chemotherapy after operation
intervention type: Other
intervention name: No intervention
arm group label: Group cap
tissue,blood,urine and stool sample
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Wansheng Chen, PhD
role: Study Chair
affiliation: Department of medicine of Shanghai Changzheng Hospital
facility: 
country: China
citation: Zhang X, Sun B, Lu Z. Evaluation of clinical value of single nucleotide polymorphisms of dihydropyrimidine dehydrogenase gene to predict 5-fluorouracil toxicity in 60 colorectal cancer patients in China. Int J Med Sci. 2013 May 20;10(7):894-902. doi: 10.7150/ijms.5556. Print 2013.
PMID: 23781135
citation: Li F, Qin X, Chen H, Qiu L, Guo Y, Liu H, Chen G, Song G, Wang X, Li F, Guo S, Wang B, Li Z. Lipid profiling for early diagnosis and progression of colorectal cancer using direct-infusion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. Rapid Commun Mass Spectrom. 2013 Jan 15;27(1):24-34. doi: 10.1002/rcm.6420.
PMID: 23239314
citation: Ikeda K, Oike Y, Shimizu T, Taguchi R. Global analysis of triacylglycerols including oxidized molecular species by reverse-phase high resolution LC/ESI-QTOF MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Sep 1;877(25):2639-47. doi: 10.1016/j.jchromb.2009.03.047. Epub 2009 Apr 7.
PMID: 19481987
citation: Denkert C, Bucher E, Hilvo M, Salek R, Oresic M, Griffin J, Brockmoller S, Klauschen F, Loibl S, Barupal DK, Budczies J, Iljin K, Nekljudova V, Fiehn O. Metabolomics of human breast cancer: new approaches for tumor typing and biomarker discovery. Genome Med. 2012 Apr 30;4(4):37. doi: 10.1186/gm336.
PMID: 22546809
citation: Wu CW, Ng SS, Dong YJ, Ng SC, Leung WW, Lee CW, Wong YN, Chan FK, Yu J, Sung JJ. Detection of miR-92a and miR-21 in stool samples as potential screening biomarkers for colorectal cancer and polyps. Gut. 2012 May;61(5):739-45. doi: 10.1136/gut.2011.239236. Epub 2011 Sep 19.
PMID: 21930727
citation: Deenen MJ, Meulendijks D, Cats A, Sechterberger MK, Severens JL, Boot H, Smits PH, Rosing H, Mandigers CM, Soesan M, Beijnen JH, Schellens JH. Upfront Genotyping of DPYD*2A to Individualize Fluoropyrimidine Therapy: A Safety and Cost Analysis. J Clin Oncol. 2016 Jan 20;34(3):227-34. doi: 10.1200/JCO.2015.63.1325. Epub 2015 Nov 16.
PMID: 26573078
citation: Huang L, Chen F, Chen Y, Yang X, Xu S, Ge S, Fu S, Chao T, Yu Q, Liao X, Hu G, Zhang P, Yuan X. Thymidine phosphorylase gene variant, platelet counts and survival in gastrointestinal cancer patients treated by fluoropyrimidines. Sci Rep. 2014 Jul 16;4:5697. doi: 10.1038/srep05697.
PMID: 25027354
responsible party type: Principal Investigator
investigator affiliation: Shanghai Changzheng Hospital
investigator full name: Wansheng Chen
investigator title: Professor, Director of Department of Pharmacy
mesh term: Colorectal Neoplasms
sharing ipd: No