<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/NCT04403867</url>
  </required_header>
  <id_info>
    <org_study_id>INT 135/19</org_study_id>
    <nct_id>NCT04403867</nct_id>
  </id_info>
  <brief_title>The Role of Micrometastasis and Isolated Tumor Cells (ITCs) in Endometrial and Cervical Cancer. A Multicenter Study.</brief_title>
  <acronym>ITCMicroUtCa</acronym>
  <official_title>The Role of Micrometastasis and Isolated Tumor Cells (ITCs) in Uterine Cancers (Endometrial/Cervical) Submitted to Sentinel Lymph Nodes (SLN) Procedure: an Observational Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fondazione IRCCS Istituto Nazionale dei Tumori, Milano</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fondazione IRCCS Istituto Nazionale dei Tumori, Milano</source>
  <oversight_info>
    <has_dmc>No</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>
      The role of small-volume lymph node disease (ITC and micro metastases) among patients with&#xD;
      endometrial or cervical cancer submitted to sentinel node (SLN) procedure is not clearly&#xD;
      defined.&#xD;
&#xD;
      This study was designed to create a dataset of patients with lymph nodal disease. Data on&#xD;
      type and volume of lymph nodal disease, therapeutic choices and oncological outcomes (DFS,&#xD;
      OS, recurrence rate) will be collected and analyzed.&#xD;
&#xD;
      This will allow to define the groups of patients who may need or for whom it can be avoided&#xD;
      any adjuvant treatment on the basis of lymph node status.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 2, 2020</start_date>
  <completion_date type="Anticipated">January 2027</completion_date>
  <primary_completion_date type="Anticipated">January 2025</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>Survival (Disease free survival [DFS], overall survival [OS])</measure>
    <time_frame>through study completion, an average of 3 years</time_frame>
    <description>Evaluation of survival outcomes according to the type and volume of lymph nodal disease</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Recurrence rate</measure>
    <time_frame>through study completion, an average of 3 year</time_frame>
    <description>Evaluation of incidence of recurrences (number of patients having a recurrence) according to the type and volume of lymph nodal disease</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Usage of adjuvant therapy in case of small-volume lymph node disease</measure>
    <time_frame>through study completion, an average of 6 months</time_frame>
    <description>Evaluation of the number of patients receiving or not receiving an adjuvant treatment (radiation therapy, chemotherapy, combinations of the two) in case of small-volume lymph node disease (ITC and micro metastasis)</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">500</enrollment>
  <condition>Endometrial Cancer</condition>
  <condition>Cervical Cancer</condition>
  <condition>Sentinel Lymph Node</condition>
  <condition>Micrometastasis</condition>
  <condition>Sentinel Lymph Node Biopsy</condition>
  <condition>Endometrium Tumor</condition>
  <condition>Endometrial Neoplasms</condition>
  <condition>Cervical Neoplasm</condition>
  <condition>Cervical Tumor</condition>
  <condition>Lymph Node Metastases</condition>
  <condition>Lymph Node Disease</condition>
  <arm_group>
    <arm_group_label>Endometrial cancer patients</arm_group_label>
    <description>Patients submitted to Sentinel Lymph Node (SLN) procedure. Patients with lymph nodal disease (macrometastasis, micrometastasis, isolated tumor cells).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cervical cancer patients</arm_group_label>
    <description>Patients submitted to Sentinel Lymph Node (SLN) procedure. Patients with lymph nodal disease (macrometastasis, micrometastasis, isolated tumor cells).</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Sentinel lymph node (SLN) biosy +/- lymphadenectomy</intervention_name>
    <description>Evaluation of type and volume of lymph nodal disease</description>
    <arm_group_label>Cervical cancer patients</arm_group_label>
    <arm_group_label>Endometrial cancer patients</arm_group_label>
    <other_name>Pathological evaluation of lymph nodes (standard H&amp;H + ultrastaging or OSNA)</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with early stage uterine (endometrial or cervical) cancer, who underwent a&#xD;
        sentinel lymph node (SLN) procedure with an identification of lymph nodes metastasis&#xD;
        (macrometastasis or low volume disease [micrometastasis and isolated tumor cells])&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Early stage endometrial cancer scheduled for SLN procedure&#xD;
&#xD;
          -  Early stage cervical cancer scheduled for SLN procedure&#xD;
&#xD;
          -  Pathological evaluation of SLNs with standard ultra-staging or one-step nucleic acid&#xD;
             amplification (OSNA) for the detection of metastasis&#xD;
&#xD;
          -  Presence of lymph nodes metastasis (macrometastasis or low volume disease&#xD;
             [micrometastasis and isolated tumor cells])&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous (&lt;5 years) or concomitant malignancy other than non-melanoma skin cancer&#xD;
&#xD;
          -  Advanced/metastatic endometrial cancer&#xD;
&#xD;
          -  Locally advanced/metastatic cervical cancer&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Female</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Fabio Martinelli, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fondazione IRCCS Istituto Nazionale dei Tumori, Milano</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Fabio Martinelli, MD</last_name>
    <phone>+390223903322</phone>
    <email>fabio.martinelli@istitutotumori.mi.it</email>
  </overall_contact>
  <location>
    <facility>
      <name>Fondazione IRCCS Istituto Nazionale dei Tumori</name>
      <address>
        <city>Milan</city>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Fabio Martinelli, MD</last_name>
      <phone>+390223903322</phone>
      <email>fabio.martinelli@istitutotumori.mi.it</email>
    </contact>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <results_reference>
    <citation>Gomez-Hidalgo NR, Ramirez PT, Ngo B, Perez-Hoyos S, Coreas N, Sanchez-Iglesias JL, Cabrera S, Franco S, Benavente AP, Gil-Moreno A. Oncologic impact of micrometastases or isolated tumor cells in sentinel lymph nodes of patients with endometrial cancer: a meta-analysis. Clin Transl Oncol. 2020 Aug;22(8):1272-1279. doi: 10.1007/s12094-019-02249-x. Epub 2019 Dec 20.</citation>
    <PMID>31863354</PMID>
  </results_reference>
  <results_reference>
    <citation>Ignatov A, Lebius C, Ignatov T, Ivros S, Knueppel R, Papathemelis T, Ortmann O, Eggemann H. Lymph node micrometastases and outcome of endometrial cancer. Gynecol Oncol. 2019 Sep;154(3):475-479. doi: 10.1016/j.ygyno.2019.07.018. Epub 2019 Jul 22.</citation>
    <PMID>31345606</PMID>
  </results_reference>
  <results_reference>
    <citation>Piedimonte S, Richer L, Souhami L, Arseneau J, Fu L, Gilbert L, Alfieri J, Jardon K, Zeng XZ. Clinical significance of isolated tumor cells and micrometastasis in low-grade, stage I endometrial cancer. J Surg Oncol. 2018 Dec;118(7):1194-1198. doi: 10.1002/jso.25259. Epub 2018 Oct 24.</citation>
    <PMID>30353577</PMID>
  </results_reference>
  <results_reference>
    <citation>Plante M, Stanleigh J, Renaud MC, Sebastianelli A, Grondin K, Gregoire J. Isolated tumor cells identified by sentinel lymph node mapping in endometrial cancer: Does adjuvant treatment matter? Gynecol Oncol. 2017 Aug;146(2):240-246. doi: 10.1016/j.ygyno.2017.05.024. Epub 2017 May 31.</citation>
    <PMID>28577885</PMID>
  </results_reference>
  <results_reference>
    <citation>Goebel EA, St Laurent JD, Nucci MR, Feltmate CM. Retrospective detection of isolated tumor cells by immunohistochemistry in sentinel lymph node biopsy performed for endometrial carcinoma: is there clinical significance? Int J Gynecol Cancer. 2020 Mar;30(3):291-298. doi: 10.1136/ijgc-2019-000934. Epub 2019 Dec 8.</citation>
    <PMID>31818860</PMID>
  </results_reference>
  <results_reference>
    <citation>Aloisi A, Casanova JM, Tseng JH, Seader KA, Nguyen NT, Alektiar KM, Makker V, Chiang S, Soslow RA, Leitao MM Jr, Abu-Rustum NR. Patterns of FIRST recurrence of stage IIIC1 endometrial cancer with no PARAAORTIC nodal assessment. Gynecol Oncol. 2018 Dec;151(3):395-400. doi: 10.1016/j.ygyno.2018.09.021. Epub 2018 Oct 2.</citation>
    <PMID>30286945</PMID>
  </results_reference>
  <results_reference>
    <citation>Nica A, Gien LT, Ferguson SE, Covens A. Does small volume metastatic lymph node disease affect long-term prognosis in early cervical cancer? Int J Gynecol Cancer. 2020 Mar;30(3):285-290. doi: 10.1136/ijgc-2019-000928. Epub 2019 Dec 22.</citation>
    <PMID>31871114</PMID>
  </results_reference>
  <results_reference>
    <citation>Delomenie M, Bonsang-Kitzis H, Bats AS, Ngo C, Balaya V, Xuan HTN, Koual M, Mathevet P, Lecuru F. The clinical implication of lymph nodes micrometastases and isolated tumor cells in patients with cervical cancer: A systematic review. Eur J Obstet Gynecol Reprod Biol. 2019 Oct;241:71-76. doi: 10.1016/j.ejogrb.2019.08.010. Epub 2019 Aug 19.</citation>
    <PMID>31450214</PMID>
  </results_reference>
  <results_reference>
    <citation>Guani B, Dorez M, Magaud L, Buenerd A, Lecuru F, Mathevet P. Impact of micrometastasis or isolated tumor cells on recurrence and survival in patients with early cervical cancer: SENTICOL Trial. Int J Gynecol Cancer. 2019 Mar;29(3):447-452. doi: 10.1136/ijgc-2018-000089. Epub 2019 Jan 4.</citation>
    <PMID>30833435</PMID>
  </results_reference>
  <results_reference>
    <citation>Cibula D, Abu-Rustum NR, Dusek L, Zikan M, Zaal A, Sevcik L, Kenter GG, Querleu D, Jach R, Bats AS, Dyduch G, Graf P, Klat J, Lacheta J, Meijer CJ, Mery E, Verheijen R, Zweemer RP. Prognostic significance of low volume sentinel lymph node disease in early-stage cervical cancer. Gynecol Oncol. 2012 Mar;124(3):496-501. doi: 10.1016/j.ygyno.2011.11.037. Epub 2011 Nov 25.</citation>
    <PMID>22120175</PMID>
  </results_reference>
  <results_reference>
    <citation>Cibula D, McCluggage WG. Sentinel lymph node (SLN) concept in cervical cancer: Current limitations and unanswered questions. Gynecol Oncol. 2019 Jan;152(1):202-207. doi: 10.1016/j.ygyno.2018.10.007. Epub 2018 Oct 11.</citation>
    <PMID>30318103</PMID>
  </results_reference>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>May 18, 2020</study_first_submitted>
  <study_first_submitted_qc>May 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 27, 2020</study_first_posted>
  <last_update_submitted>August 15, 2022</last_update_submitted>
  <last_update_submitted_qc>August 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 17, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fondazione IRCCS Istituto Nazionale dei Tumori, Milano</investigator_affiliation>
    <investigator_full_name>Fabio Martinelli</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>endometrial cancer</keyword>
  <keyword>cervical cancer</keyword>
  <keyword>sentinel lymph node</keyword>
  <keyword>low volume disease</keyword>
  <keyword>survival</keyword>
  <keyword>recurrence rate</keyword>
  <keyword>adjuvant therapy</keyword>
  <keyword>micrometastases</keyword>
  <keyword>isolated tumor cell</keyword>
  <keyword>macrometastases</keyword>
  <keyword>ultrastaging</keyword>
  <keyword>one-step nucleic acid amplification (OSNA)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Uterine Cervical Neoplasms</mesh_term>
    <mesh_term>Endometrial Neoplasms</mesh_term>
    <mesh_term>Lymphatic Metastasis</mesh_term>
    <mesh_term>Neoplasm Micrometastasis</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/NCT04403867
org study id: INT 135/19
nct id: NCT04403867
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The role of small-volume lymph node disease (ITC and micro metastases) among patients with
      endometrial or cervical cancer submitted to sentinel node (SLN) procedure is not clearly
      defined.

      This study was designed to create a dataset of patients with lymph nodal disease. Data on
      type and volume of lymph nodal disease, therapeutic choices and oncological outcomes (DFS,
      OS, recurrence rate) will be collected and analyzed.

      This will allow to define the groups of patients who may need or for whom it can be avoided
      any adjuvant treatment on the basis of lymph node status.
observational model: Cohort
time perspective: Retrospective
measure: Survival (Disease free survival [DFS], overall survival [OS])
time frame: through study completion, an average of 3 years
description: Evaluation of survival outcomes according to the type and volume of lymph nodal disease
measure: Recurrence rate
time frame: through study completion, an average of 3 year
description: Evaluation of incidence of recurrences (number of patients having a recurrence) according to the type and volume of lymph nodal disease
measure: Usage of adjuvant therapy in case of small-volume lymph node disease
time frame: through study completion, an average of 6 months
description: Evaluation of the number of patients receiving or not receiving an adjuvant treatment (radiation therapy, chemotherapy, combinations of the two) in case of small-volume lymph node disease (ITC and micro metastasis)
arm group label: Endometrial cancer patients
description: Patients submitted to Sentinel Lymph Node (SLN) procedure. Patients with lymph nodal disease (macrometastasis, micrometastasis, isolated tumor cells).
arm group label: Cervical cancer patients
description: Patients submitted to Sentinel Lymph Node (SLN) procedure. Patients with lymph nodal disease (macrometastasis, micrometastasis, isolated tumor cells).
intervention type: Procedure
intervention name: Sentinel lymph node (SLN) biosy +/- lymphadenectomy
description: Evaluation of type and volume of lymph nodal disease
arm group label: Cervical cancer patients
arm group label: Endometrial cancer patients
other name: Pathological evaluation of lymph nodes (standard H&H + ultrastaging or OSNA)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
gender based: Yes
gender description: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Fabio Martinelli, MD
role: Principal Investigator
affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
last name: Fabio Martinelli, MD
phone: +390223903322
email: fabio.martinelli@istitutotumori.mi.it
facility: 
status: Recruiting
contact: 
country: Italy
citation: Gomez-Hidalgo NR, Ramirez PT, Ngo B, Perez-Hoyos S, Coreas N, Sanchez-Iglesias JL, Cabrera S, Franco S, Benavente AP, Gil-Moreno A. Oncologic impact of micrometastases or isolated tumor cells in sentinel lymph nodes of patients with endometrial cancer: a meta-analysis. Clin Transl Oncol. 2020 Aug;22(8):1272-1279. doi: 10.1007/s12094-019-02249-x. Epub 2019 Dec 20.
PMID: 31863354
citation: Ignatov A, Lebius C, Ignatov T, Ivros S, Knueppel R, Papathemelis T, Ortmann O, Eggemann H. Lymph node micrometastases and outcome of endometrial cancer. Gynecol Oncol. 2019 Sep;154(3):475-479. doi: 10.1016/j.ygyno.2019.07.018. Epub 2019 Jul 22.
PMID: 31345606
citation: Piedimonte S, Richer L, Souhami L, Arseneau J, Fu L, Gilbert L, Alfieri J, Jardon K, Zeng XZ. Clinical significance of isolated tumor cells and micrometastasis in low-grade, stage I endometrial cancer. J Surg Oncol. 2018 Dec;118(7):1194-1198. doi: 10.1002/jso.25259. Epub 2018 Oct 24.
PMID: 30353577
citation: Plante M, Stanleigh J, Renaud MC, Sebastianelli A, Grondin K, Gregoire J. Isolated tumor cells identified by sentinel lymph node mapping in endometrial cancer: Does adjuvant treatment matter? Gynecol Oncol. 2017 Aug;146(2):240-246. doi: 10.1016/j.ygyno.2017.05.024. Epub 2017 May 31.
PMID: 28577885
citation: Goebel EA, St Laurent JD, Nucci MR, Feltmate CM. Retrospective detection of isolated tumor cells by immunohistochemistry in sentinel lymph node biopsy performed for endometrial carcinoma: is there clinical significance? Int J Gynecol Cancer. 2020 Mar;30(3):291-298. doi: 10.1136/ijgc-2019-000934. Epub 2019 Dec 8.
PMID: 31818860
citation: Aloisi A, Casanova JM, Tseng JH, Seader KA, Nguyen NT, Alektiar KM, Makker V, Chiang S, Soslow RA, Leitao MM Jr, Abu-Rustum NR. Patterns of FIRST recurrence of stage IIIC1 endometrial cancer with no PARAAORTIC nodal assessment. Gynecol Oncol. 2018 Dec;151(3):395-400. doi: 10.1016/j.ygyno.2018.09.021. Epub 2018 Oct 2.
PMID: 30286945
citation: Nica A, Gien LT, Ferguson SE, Covens A. Does small volume metastatic lymph node disease affect long-term prognosis in early cervical cancer? Int J Gynecol Cancer. 2020 Mar;30(3):285-290. doi: 10.1136/ijgc-2019-000928. Epub 2019 Dec 22.
PMID: 31871114
citation: Delomenie M, Bonsang-Kitzis H, Bats AS, Ngo C, Balaya V, Xuan HTN, Koual M, Mathevet P, Lecuru F. The clinical implication of lymph nodes micrometastases and isolated tumor cells in patients with cervical cancer: A systematic review. Eur J Obstet Gynecol Reprod Biol. 2019 Oct;241:71-76. doi: 10.1016/j.ejogrb.2019.08.010. Epub 2019 Aug 19.
PMID: 31450214
citation: Guani B, Dorez M, Magaud L, Buenerd A, Lecuru F, Mathevet P. Impact of micrometastasis or isolated tumor cells on recurrence and survival in patients with early cervical cancer: SENTICOL Trial. Int J Gynecol Cancer. 2019 Mar;29(3):447-452. doi: 10.1136/ijgc-2018-000089. Epub 2019 Jan 4.
PMID: 30833435
citation: Cibula D, Abu-Rustum NR, Dusek L, Zikan M, Zaal A, Sevcik L, Kenter GG, Querleu D, Jach R, Bats AS, Dyduch G, Graf P, Klat J, Lacheta J, Meijer CJ, Mery E, Verheijen R, Zweemer RP. Prognostic significance of low volume sentinel lymph node disease in early-stage cervical cancer. Gynecol Oncol. 2012 Mar;124(3):496-501. doi: 10.1016/j.ygyno.2011.11.037. Epub 2011 Nov 25.
PMID: 22120175
citation: Cibula D, McCluggage WG. Sentinel lymph node (SLN) concept in cervical cancer: Current limitations and unanswered questions. Gynecol Oncol. 2019 Jan;152(1):202-207. doi: 10.1016/j.ygyno.2018.10.007. Epub 2018 Oct 11.
PMID: 30318103
responsible party type: Principal Investigator
investigator affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
investigator full name: Fabio Martinelli
investigator title: Principal Investigator
mesh term: Neoplasms
mesh term: Uterine Cervical Neoplasms
mesh term: Endometrial Neoplasms
mesh term: Lymphatic Metastasis
mesh term: Neoplasm Micrometastasis