<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/NCT02979470</url>
  </required_header>
  <id_info>
    <org_study_id>CEP2141/15</org_study_id>
    <nct_id>NCT02979470</nct_id>
  </id_info>
  <brief_title>Study of Blood Components as Probable Prognostic and Predictive Markers of Response to Treatment in Advanced Colon and Rectal Cancers</brief_title>
  <acronym>BMACR</acronym>
  <official_title>Study of Blood Components as Probable Prognostic and Predictive Markers of Response to Treatment in Advanced Colon and Rectal Cancers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AC Camargo Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AC Camargo Cancer Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main reason of cancer-related mortality is the spread of cancer cells to distant sites&#xD;
      (micrometastases). However, only a few small groups of tumor cells can metastasize by&#xD;
      acquiring mechanism to decrease the immune response. Changes in the systemic inflammatory&#xD;
      response to the tumor can be measured by blood-based parameters. In particular, the&#xD;
      proportion of neutrophyls- lymphocytes (NL) has been evaluated for predicting the survival of&#xD;
      patients with different types of cancer. The first strategy to treat colorectal cancer (CCR)&#xD;
      is complete resection of the lesion. Nevertheless, some patients experience recurrence,&#xD;
      probably due to residual micrometastases. We have demonstrated that analysis of some&#xD;
      resistance proteins (Tyms / MRP1) in circulating tumor cells (CTCs) may predict treatment&#xD;
      response in metastatic CCR patients (mCRC). We also note that the CTCs kinetics can show&#xD;
      response to therapy. Patients with stage III disease in the colon / rectum, although showing&#xD;
      high cure rate, generally fall locally or remotely and studies with blood markers in this&#xD;
      group of patients is still scarce. Primary Objective: To investigate cells found in the blood&#xD;
      (lymphocytes and neutrophils and CTCs) to verify if they can help in the choice of&#xD;
      anti-neoplastic therapy in patients with advanced colon and rectum cancers. Secondary&#xD;
      objectives: - to evaluate the influence of CTC kinetics in response to treatment of patients&#xD;
      with advanced colon/rectum cancers; - to check the expression of treatment resistance,&#xD;
      invasion and proliferation proteins (Tyms, TGF-βR, MMP-2, β-gal, Ki-67 and CD45) in CTCs and&#xD;
      their correlation with response to treatment; - to check the mRNA expression of the same&#xD;
      genes observed by immunocytochemistry in CTCs and their correlation with response to&#xD;
      treatment; - to quantify CTCs, neutrophils and lymphocytes of patients included in this study&#xD;
      and verify if there are correlation among their rates and progression-free survival. Methods:&#xD;
      there will be collected 10 ml of blood of patients with advanced colon and rectal cancer for&#xD;
      analysis of CTCs, lymphocytes / neutrophils. CTCs will be isolated, quantified and analyzed&#xD;
      after separation by ISET method (Rarecells/France). The marker analysis of these cells will&#xD;
      be done by immunocytochemistry and the gene expression will be assessed by RNAscope. The&#xD;
      quantification of lymphocytes/neutrophils will be made by common blood count in Delboni&#xD;
      laboratory. Expected Results: We propose to show that not only the count and the kinetics of&#xD;
      CTCs, but also their molecular characteristics, can provide relevant information to&#xD;
      clinicians. Hopefully, by quantification of neutrophils and lymphocytes, we will be able to&#xD;
      identify new prognostic blood biomarkers that can direct clinicians to the best therapeutic&#xD;
      choice.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>September 2016</start_date>
  <completion_date type="Anticipated">September 2019</completion_date>
  <primary_completion_date type="Anticipated">September 2018</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>12 Months</target_duration>
  <primary_outcome>
    <measure>progression free survival</measure>
    <time_frame>24 months</time_frame>
    <description>time between first blood collection for CTC´s analysis and first progression</description>
  </primary_outcome>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Colon Cancer Stage IIb</condition>
  <condition>Rectum Cancer, Adenocarcinoma</condition>
  <condition>Colon Cancer Stage IIIa</condition>
  <condition>Colon Cancer Stage IIIc</condition>
  <condition>Colon Cancer Stage IIIb</condition>
  <eligibility>
    <study_pop>
      <textblock>
        colon (EC III) or rectum (EC II and III) cancer patients&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:- ECOG (Eastern Cooperative Oncology Group) Performance Status between 0&#xD;
        and 2; - patients undergoing surgery followed by adjuvant chemotherapy (locally advanced&#xD;
        colon cancer) or initiating neoadjuvant chemotherapy followed by surgery (locally advanced&#xD;
        rectal cancer); - disease measurable by RECIST criteria 1.1 (Response Evaluation Criteria&#xD;
        in Solid Tumors); - medullary function assessed by peripheral blood sample considered&#xD;
        normal; Renal and hepatic function tests up to 1.5 times the limit of normality.&#xD;
&#xD;
        -&#xD;
&#xD;
        Exclusion Criteria:Patients younger than 18 years; -patients who have had surgery or&#xD;
        surgical procedure in the last week; - patients who have had previous therapy in the last&#xD;
        three weeks; - patients with previous history of another carcinoma in the last two years; -&#xD;
        refuses to sign the TCLE&#xD;
&#xD;
        -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ludmilla Chinen, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>AC Camargo Cancer Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ludmilla Chinen, PhD</last_name>
    <phone>551121895000</phone>
    <phone_ext>2776</phone_ext>
    <email>ludmilla.chinen@cipe.accamargo.org.br</email>
  </overall_contact>
  <location>
    <facility>
      <name>ACCamargo Cancer Center</name>
      <address>
        <city>Sao Paulo</city>
        <state>SP</state>
        <zip>01509900</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ludmilla Chinen, PhD</last_name>
      <phone>1121895000</phone>
      <phone_ext>2776</phone_ext>
      <email>ludmilla.chinen@cipe.accamargo.org.br</email>
    </contact>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <results_reference>
    <citation>Abdallah EA, Fanelli MF, Souza E Silva V, Machado Netto MC, Gasparini Junior JL, Araujo DV, Ocea LM, Buim ME, Tariki MS, Alves Vda S, Piana de Andrade V, Dettino AL, Abdon Lopes de Mello C, Chinen LT. MRP1 expression in CTCs confers resistance to irinotecan-based chemotherapy in metastatic colorectal cancer. Int J Cancer. 2016 Aug 15;139(4):890-8. doi: 10.1002/ijc.30082. Epub 2016 Apr 28.</citation>
    <PMID>26950035</PMID>
  </results_reference>
  <results_reference>
    <citation>Abdallah EA, Fanelli MF, Buim ME, Machado Netto MC, Gasparini Junior JL, Souza E Silva V, Dettino AL, Mingues NB, Romero JV, Ocea LM, Rocha BM, Alves VS, Araujo DV, Chinen LT. Thymidylate synthase expression in circulating tumor cells: a new tool to predict 5-fluorouracil resistance in metastatic colorectal cancer patients. Int J Cancer. 2015 Sep 15;137(6):1397-405. doi: 10.1002/ijc.29495. Epub 2015 Mar 11.</citation>
    <PMID>25721610</PMID>
  </results_reference>
  <verification_date>June 2018</verification_date>
  <study_first_submitted>November 29, 2016</study_first_submitted>
  <study_first_submitted_qc>November 30, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 1, 2016</study_first_posted>
  <last_update_submitted>June 29, 2018</last_update_submitted>
  <last_update_submitted_qc>June 29, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 2, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>AC Camargo Cancer Center</investigator_affiliation>
    <investigator_full_name>Ludmilla Thome Domingos Chinen, PhD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>advanced colon cancer</keyword>
  <keyword>advanced rectum cancer</keyword>
  <keyword>circulating tumor cells</keyword>
  <keyword>immune response</keyword>
  <keyword>mutations</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rectal Neoplasms</mesh_term>
    <mesh_term>Colonic 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/NCT02979470
org study id: CEP2141/15
nct id: NCT02979470
lead sponsor: 
has dmc: Yes
The main reason of cancer-related mortality is the spread of cancer cells to distant sites
      (micrometastases). However, only a few small groups of tumor cells can metastasize by
      acquiring mechanism to decrease the immune response. Changes in the systemic inflammatory
      response to the tumor can be measured by blood-based parameters. In particular, the
      proportion of neutrophyls- lymphocytes (NL) has been evaluated for predicting the survival of
      patients with different types of cancer. The first strategy to treat colorectal cancer (CCR)
      is complete resection of the lesion. Nevertheless, some patients experience recurrence,
      probably due to residual micrometastases. We have demonstrated that analysis of some
      resistance proteins (Tyms / MRP1) in circulating tumor cells (CTCs) may predict treatment
      response in metastatic CCR patients (mCRC). We also note that the CTCs kinetics can show
      response to therapy. Patients with stage III disease in the colon / rectum, although showing
      high cure rate, generally fall locally or remotely and studies with blood markers in this
      group of patients is still scarce. Primary Objective: To investigate cells found in the blood
      (lymphocytes and neutrophils and CTCs) to verify if they can help in the choice of
      anti-neoplastic therapy in patients with advanced colon and rectum cancers. Secondary
      objectives: - to evaluate the influence of CTC kinetics in response to treatment of patients
      with advanced colon/rectum cancers; - to check the expression of treatment resistance,
      invasion and proliferation proteins (Tyms, TGF-βR, MMP-2, β-gal, Ki-67 and CD45) in CTCs and
      their correlation with response to treatment; - to check the mRNA expression of the same
      genes observed by immunocytochemistry in CTCs and their correlation with response to
      treatment; - to quantify CTCs, neutrophils and lymphocytes of patients included in this study
      and verify if there are correlation among their rates and progression-free survival. Methods:
      there will be collected 10 ml of blood of patients with advanced colon and rectal cancer for
      analysis of CTCs, lymphocytes / neutrophils. CTCs will be isolated, quantified and analyzed
      after separation by ISET method (Rarecells/France). The marker analysis of these cells will
      be done by immunocytochemistry and the gene expression will be assessed by RNAscope. The
      quantification of lymphocytes/neutrophils will be made by common blood count in Delboni
      laboratory. Expected Results: We propose to show that not only the count and the kinetics of
      CTCs, but also their molecular characteristics, can provide relevant information to
      clinicians. Hopefully, by quantification of neutrophils and lymphocytes, we will be able to
      identify new prognostic blood biomarkers that can direct clinicians to the best therapeutic
      choice.
observational model: Cohort
time perspective: Prospective
measure: progression free survival
time frame: 24 months
description: time between first blood collection for CTC´s analysis and first progression
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ludmilla Chinen, PhD
role: Principal Investigator
affiliation: AC Camargo Cancer Center
last name: Ludmilla Chinen, PhD
phone: 551121895000
phone ext: 2776
email: ludmilla.chinen@cipe.accamargo.org.br
facility: 
status: Recruiting
contact: 
country: Brazil
citation: Abdallah EA, Fanelli MF, Souza E Silva V, Machado Netto MC, Gasparini Junior JL, Araujo DV, Ocea LM, Buim ME, Tariki MS, Alves Vda S, Piana de Andrade V, Dettino AL, Abdon Lopes de Mello C, Chinen LT. MRP1 expression in CTCs confers resistance to irinotecan-based chemotherapy in metastatic colorectal cancer. Int J Cancer. 2016 Aug 15;139(4):890-8. doi: 10.1002/ijc.30082. Epub 2016 Apr 28.
PMID: 26950035
citation: Abdallah EA, Fanelli MF, Buim ME, Machado Netto MC, Gasparini Junior JL, Souza E Silva V, Dettino AL, Mingues NB, Romero JV, Ocea LM, Rocha BM, Alves VS, Araujo DV, Chinen LT. Thymidylate synthase expression in circulating tumor cells: a new tool to predict 5-fluorouracil resistance in metastatic colorectal cancer patients. Int J Cancer. 2015 Sep 15;137(6):1397-405. doi: 10.1002/ijc.29495. Epub 2015 Mar 11.
PMID: 25721610
responsible party type: Principal Investigator
investigator affiliation: AC Camargo Cancer Center
investigator full name: Ludmilla Thome Domingos Chinen, PhD
investigator title: Principal Investigator
mesh term: Rectal Neoplasms
mesh term: Colonic Neoplasms
sharing ipd: No