<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/NCT03778268</url>
  </required_header>
  <id_info>
    <org_study_id>2018PHD003-01</org_study_id>
    <nct_id>NCT03778268</nct_id>
  </id_info>
  <brief_title>Sentinel Lymph Node Mapping In Cervical Cancer</brief_title>
  <acronym>SLNMICC</acronym>
  <official_title>Comparing the Diagnostic Value of Different Lymph Node Tracing Methods in Detecting Sentinel Lymph Node Metastasis in Early Cervical Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking University People's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Peking University International Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shanghai First Maternity and Infant Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Obstetrics &amp; Gynecology Hospital of Fudan University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sun Yat-sen University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Tianjin Central Hospital of Gynecology Obstetrics</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Cancer Hospital of Guangxi Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>First People's Hospital of Foshan</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The First Affiliated Hospital of Zhengzhou University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Second Affiliated Hospital of Zhengzhou University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Beijing Blue Sky Shared Health Management Co., Ltd.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Chongqing Lummy Pharmaceutical Co.,Ltd.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Peking University People's 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>
      Lymph node assessment provides the crucial information about the prognosis of cervical&#xD;
      cancer. Sentinel lymph node stands in the first station on the lymph node metastasis&#xD;
      pathways. While traditional systemically lymph node resection would bring a lot of&#xD;
      complications, sentinel node mapping and biopsy is a feasible way with less damage to&#xD;
      evaluate whether lymph node metastasis occurs in early cervical cancer patients, due to less&#xD;
      lymph nodes resected. However, the process of this technology isn't well established. The&#xD;
      investigators intend to conduct a prospective and multicentric study to evaluate the&#xD;
      effectiveness of different mapping methods to achieve a reliable lymph node assessment. Early&#xD;
      cervical cancer patients in each center will be recruited in the investigators' study with&#xD;
      inclusion and exclusion criteria. After the patients signing the informed consent form, the&#xD;
      surgery process will be performed, including sentinel lymph node mapping with Carbon&#xD;
      Nanoparticles (CNP) or CNP combining Indocyanine Green(ICG),&#xD;
      extra-fascial/sub-extensive/extensive hysterectomy, pelvic with or without para-aortic lymph&#xD;
      node resection, sequentially. All resected nodes will be pathologically exanimated. Then the&#xD;
      data obtained will be analyzed and discussed deeply and finally lead to a conclusion.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Quality Control The investigators' quality assurance plan is as follows： A. Once the plan has&#xD;
      been approved, it cannot be modified at will. If special circumstances such as difficulty in&#xD;
      implementation are found after the start of the study, the proposal may be revised or&#xD;
      supplemented by the discussion of the research group and the project leader, and the revised&#xD;
      content shall be recorded in writing.&#xD;
&#xD;
      The program change process is as follows:&#xD;
&#xD;
        -  Identify the problems and understand the necessary to change the plan;&#xD;
&#xD;
        -  Convene the main members of the research team and the project leader to discuss and&#xD;
           propose solutions;&#xD;
&#xD;
        -  Revise the plan and update the version number, fill out the &quot;Program Description&quot;;&#xD;
&#xD;
        -  The revised plan and the &quot;Revision of the Plan&quot; need to be signed by the person in&#xD;
           charge of the project. If necessary, they must be submitted to the ethics committee for&#xD;
           approval or filing; if approved, the revised plan can be implemented.&#xD;
&#xD;
      B. In order to ensure that the research personnel have sufficient qualifications to undertake&#xD;
      specific research work, the research personnel should at least complete the following&#xD;
      training before the project starts:&#xD;
&#xD;
        -  Research object protection and ethical requirements;&#xD;
&#xD;
        -  Study protocols and related standard operating procedures (tracer injection methods, use&#xD;
           of near-infrared fluorescent vascular imagers, and pathology);&#xD;
&#xD;
        -  Case Report Form and gauge filling instructions (form entry criteria, surgical record&#xD;
           methods, etc.);&#xD;
&#xD;
        -  Clinical research project implementation considerations (such as research object&#xD;
           screening, enrollment, data collection process); Project-related training should be&#xD;
           carried out throughout the research process. The project leader and project coordinator&#xD;
           can increase the training content according to the situation, such as training on weak&#xD;
           links in the test, training on updating programs and various causes.&#xD;
&#xD;
      Data Management A. Case report form design The researcher is responsible for drafting the&#xD;
      research case report form. B. Data Entry and Data Verification According to the final version&#xD;
      of CRF, the project database is built using software. The data entry and verification is&#xD;
      carried out by a dedicated person.&#xD;
&#xD;
      Statistical Analysis A. Statistical Analysis Plan and Statistical Software After the trial&#xD;
      protocol is determined, the statistical professors and the main investigators are responsible&#xD;
      for developing a statistical analysis plan. The statistical analysis software uses SAS® 9.2&#xD;
      software (software installation point authorization number: 11202165).&#xD;
&#xD;
      B. Calculation and reasoning of sample size The sample size is calculated using PASS11&#xD;
      software; the sample size is estimated based on the negative prediction value of the previous&#xD;
      study, and the negative prediction value of SLNs is expected to be 90%; the allowable error&#xD;
      is 2% (the range of the confidence interval is 88% to 92%). When the significant level is&#xD;
      0.05, 914 cases are needed to be studied. Considering the detection rate of 80% of SLNs, a&#xD;
      total of 1143 cases are expected to be studied.&#xD;
&#xD;
      C. Statistical Analysis Methods General principle Using a two-sided test, a P value of less&#xD;
      than 0.05 would be considered statistically significant.&#xD;
&#xD;
      The quantitative indicators will calculate the mean, standard deviation, median, minimum,&#xD;
      maximum, lower quartile (Q1), upper quartile (Q3), and the classification indicators will&#xD;
      describe the number of cases and percentages.&#xD;
&#xD;
      Comparison of clinicopathological features (age, body mass index, pathological type, tumor&#xD;
      stage, grading, maximum tumor diameter, invasive myometrial depth, lymphatic vascular&#xD;
      infiltration, and tracer method) for SLNs and undetected SLNs will be based on the type of&#xD;
      indicator. For the comparison of quantitative data between groups, the t-test or Wilcoxon&#xD;
      rank sum test will be used according to the data distribution. For the comparison of&#xD;
      categorical data between groups, the data will be analyzed by chi-square test or exact&#xD;
      probability method (if the chi-square test is not applicable). And the grade data was&#xD;
      analyzed by Wilcoxon rank sum test or CMH test.&#xD;
&#xD;
      Clinical diagnostic index calculation According to the true positive (TP), false negative&#xD;
      (FN), true negative (TN), and false positive (FP), the results of SLNs pathological&#xD;
      examination and all lymph node pathological examination results will be compared. The&#xD;
      comparison results will be plotted as a four-grid table to calculate sensitivity, false&#xD;
      negative rate, and negative predictive value, respectively.&#xD;
&#xD;
      Chi-square test or exact probability method (if the chi-square test is not applicable) will&#xD;
      be used to compare the clinical diagnosis value of SLNs biopsy of endometrial cancer patients&#xD;
      with injection of carbon nanoparticles (CNP) or combined injection of CNP and indocyanine&#xD;
      green(ICG).&#xD;
&#xD;
      Chi-square test or exact probability method (if the chi-square test is not applicable) will&#xD;
      be used to analyze the clinic-pathological factors affecting the detection rate of SLNs.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Anticipated">December 15, 2018</start_date>
  <completion_date type="Anticipated">June 30, 2020</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>The procedure is listed as follows:&#xD;
Recruiting early stage cervical cancer patients undergoing extra-fascial/sub-extensive/extensive hysterectomy, pelvic with or without aortic lymph node resection from July 2018 to June 2020.&#xD;
Selecting the Standard-compliant patients according to the inclusion and exclusion criteria.&#xD;
Numbering the above patients and collecting their clinical data.&#xD;
Injecting carbon nanoparticles (CNP)[Not Equipped with near-infrared fluorescent vascular imager] or CNP combining Indocyanine Green(ICG)[Equipped with near-infrared fluorescent vascular imager].&#xD;
Identifying and removing sentinel lymph nodes.&#xD;
Completing the total hysterectomy, biadnexectomy and pelvic with or without para-aortic lymphadenectomy.&#xD;
Staining all nodes using hematoxylin-eosin staining.&#xD;
Calculating the sensitivity, negative predictive value, etc.</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Negative Predictive Value</measure>
    <time_frame>Through study completion, an average of 2 years</time_frame>
    <description>Sentinel lymph node detection is defined as at least one lymph node is found in a patient. Sentinel lymph node negative is defined as no sentinel lymph node detected. True negative is defined as no metastasis found in both sentinel lymph nodes (SLNs) and non-SLNs. Negative predictive value is defined as the proportion of true negative patients to SLNs negative patients in patients with sentinel lymph nodes detected, which means patients without SLNs detected won't be included in the calculation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>SLNs detection rate</measure>
    <time_frame>Through study completion, an average of 2 years</time_frame>
    <description>Sentinel lymph node detection is defined as at least one lymph node is found in a patient. The detection rate is the proportion of the patients with SLNs detected in all enrolled patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sensitivity</measure>
    <time_frame>Through study completion, an average of 2 years</time_frame>
    <description>Sensitivity is defined as the proportion of the SLNs positive patients in patients with SLNs or non-SLNs lymphatic metastasis (among the patients with SLNs detected)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>False negative rate</measure>
    <time_frame>Through study completion, an average of 2 years</time_frame>
    <description>False negative is defined as no metastasis found in SLNs while metastasis found in non-SLNs. False negative rate is defined as the proportion of the false negative patients in the patients with SLNs or non-SLNs lymphatic metastasis(among the patients with SLNs detected)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">1143</enrollment>
  <condition>Uterine Cervical Neoplasms</condition>
  <arm_group>
    <arm_group_label>Undergoing sentinel lymph node biopsy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This group of patients will undergo sentinel lymph node biopsy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>sentinel lymph node biopsy</intervention_name>
    <description>Injecting carbon nanoparticles (CNP)[Not Equipped with near-infrared fluorescent vascular imager] or CNP combining Indocyanine Green(ICG)[Equipped with near-infrared fluorescent vascular imager].&#xD;
Identifying and removing sentinel lymph nodes.&#xD;
Staining all nodes using hematoxylin-eosin staining.</description>
    <arm_group_label>Undergoing sentinel lymph node biopsy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of early cervical cancer (FIGO IA1 with LVSI (+) to IIA).&#xD;
&#xD;
          -  Decide to receive extra-fascial/sub-extensive/extensive hysterectomy, pelvic with or&#xD;
             without aortic lymph node resection&#xD;
&#xD;
          -  Agree to conduct the study and sign an informed consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of cervical cancer in FIGO IIB stage and above&#xD;
&#xD;
          -  History of previous pelvic or inguinal lymphadenectomy or other history of surgery&#xD;
             affecting the uterine lymphatic drainage&#xD;
&#xD;
          -  Other history of pelvic or abdominal malignant tumors in the past 5 years&#xD;
&#xD;
          -  Intolerable for surgery due to severe comorbidities&#xD;
&#xD;
          -  During a period of pregnancy&#xD;
&#xD;
          -  Allergic to the tracer&#xD;
&#xD;
          -  Diagnosis of uncontrolled epilepsy, central nervous system disease or mental disorder,&#xD;
             with the judgment from the investigator that the above diseases would affect clinical&#xD;
             research compliance.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jianliu Wang, Professor</last_name>
    <role>Study Director</role>
    <affiliation>Peking University People's Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jianliu Wang, Professor</last_name>
    <phone>88324385</phone>
    <phone_ext>010</phone_ext>
    <email>wangjianliu@pku.edu.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>Peking University People's Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100044</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jianliu Wang, Professor</last_name>
    </contact>
    <investigator>
      <last_name>Desheng Yao, Professor</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jihong Liu, Professor</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Wuliang Wang, Professor</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ruixia Guo, Professor</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Yongjun Wang, Professor</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Xiaojun Chen, Professor</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Bin Li, Professor</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Gang Wang, Professor</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Yuanjing Hu, Professor</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Xiaoping Wan, Professor</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Peking University People's Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100044</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015 Mar 1;136(5):E359-86. doi: 10.1002/ijc.29210. Epub 2014 Oct 9.</citation>
    <PMID>25220842</PMID>
  </reference>
  <reference>
    <citation>Creasman WT, Morrow CP, Bundy BN, Homesley HD, Graham JE, Heller PB. Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study. Cancer. 1987 Oct 15;60(8 Suppl):2035-41. doi: 10.1002/1097-0142(19901015)60:8+3.0.co;2-8.</citation>
    <PMID>3652025</PMID>
  </reference>
  <reference>
    <citation>NCCN Guidelines Version 1. 2018. Cervical Cancer [EB/OL]. [2018-02-10]. http://www.nccn.org/professionals/physician_gls/pdf/cervical.pdf.</citation>
  </reference>
  <reference>
    <citation>Lu Y, Wei JY, Yao DS, Pan ZM, Yao Y. Application of carbon nanoparticles in laparoscopic sentinel lymph node detection in patients with early-stage cervical cancer. PLoS One. 2017 Sep 5;12(9):e0183834. doi: 10.1371/journal.pone.0183834. eCollection 2017.</citation>
    <PMID>28873443</PMID>
  </reference>
  <reference>
    <citation>Holloway RW, Abu-Rustum NR, Backes FJ, Boggess JF, Gotlieb WH, Jeffrey Lowery W, Rossi EC, Tanner EJ, Wolsky RJ. Sentinel lymph node mapping and staging in endometrial cancer: A Society of Gynecologic Oncology literature review with consensus recommendations. Gynecol Oncol. 2017 Aug;146(2):405-415. doi: 10.1016/j.ygyno.2017.05.027. Epub 2017 May 28.</citation>
    <PMID>28566221</PMID>
  </reference>
  <reference>
    <citation>Liang SC, Wang ZQ, Wang JL. [Clinical analysis of 76 cases of sentinel lymph node detection in cervical cancer and endometrial cancer]. Zhonghua Fu Chan Ke Za Zhi. 2017 Sep 25;52(9):605-611. doi: 10.3760/cma.j.issn.0529-567X.2017.09.006. Chinese.</citation>
    <PMID>28954449</PMID>
  </reference>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 13, 2018</study_first_submitted>
  <study_first_submitted_qc>December 15, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>December 15, 2018</last_update_submitted>
  <last_update_submitted_qc>December 15, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 19, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Sentinel Lymph Node Biopsy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Uterine Cervical Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
  </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/NCT03778268
org study id: 2018PHD003-01
nct id: NCT03778268
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Lymph node assessment provides the crucial information about the prognosis of cervical
      cancer. Sentinel lymph node stands in the first station on the lymph node metastasis
      pathways. While traditional systemically lymph node resection would bring a lot of
      complications, sentinel node mapping and biopsy is a feasible way with less damage to
      evaluate whether lymph node metastasis occurs in early cervical cancer patients, due to less
      lymph nodes resected. However, the process of this technology isn't well established. The
      investigators intend to conduct a prospective and multicentric study to evaluate the
      effectiveness of different mapping methods to achieve a reliable lymph node assessment. Early
      cervical cancer patients in each center will be recruited in the investigators' study with
      inclusion and exclusion criteria. After the patients signing the informed consent form, the
      surgery process will be performed, including sentinel lymph node mapping with Carbon
      Nanoparticles (CNP) or CNP combining Indocyanine Green(ICG),
      extra-fascial/sub-extensive/extensive hysterectomy, pelvic with or without para-aortic lymph
      node resection, sequentially. All resected nodes will be pathologically exanimated. Then the
      data obtained will be analyzed and discussed deeply and finally lead to a conclusion.
Quality Control The investigators' quality assurance plan is as follows： A. Once the plan has
      been approved, it cannot be modified at will. If special circumstances such as difficulty in
      implementation are found after the start of the study, the proposal may be revised or
      supplemented by the discussion of the research group and the project leader, and the revised
      content shall be recorded in writing.

      The program change process is as follows:

        -  Identify the problems and understand the necessary to change the plan;

        -  Convene the main members of the research team and the project leader to discuss and
           propose solutions;

        -  Revise the plan and update the version number, fill out the "Program Description";

        -  The revised plan and the "Revision of the Plan" need to be signed by the person in
           charge of the project. If necessary, they must be submitted to the ethics committee for
           approval or filing; if approved, the revised plan can be implemented.

      B. In order to ensure that the research personnel have sufficient qualifications to undertake
      specific research work, the research personnel should at least complete the following
      training before the project starts:

        -  Research object protection and ethical requirements;

        -  Study protocols and related standard operating procedures (tracer injection methods, use
           of near-infrared fluorescent vascular imagers, and pathology);

        -  Case Report Form and gauge filling instructions (form entry criteria, surgical record
           methods, etc.);

        -  Clinical research project implementation considerations (such as research object
           screening, enrollment, data collection process); Project-related training should be
           carried out throughout the research process. The project leader and project coordinator
           can increase the training content according to the situation, such as training on weak
           links in the test, training on updating programs and various causes.

      Data Management A. Case report form design The researcher is responsible for drafting the
      research case report form. B. Data Entry and Data Verification According to the final version
      of CRF, the project database is built using software. The data entry and verification is
      carried out by a dedicated person.

      Statistical Analysis A. Statistical Analysis Plan and Statistical Software After the trial
      protocol is determined, the statistical professors and the main investigators are responsible
      for developing a statistical analysis plan. The statistical analysis software uses SAS® 9.2
      software (software installation point authorization number: 11202165).

      B. Calculation and reasoning of sample size The sample size is calculated using PASS11
      software; the sample size is estimated based on the negative prediction value of the previous
      study, and the negative prediction value of SLNs is expected to be 90%; the allowable error
      is 2% (the range of the confidence interval is 88% to 92%). When the significant level is
      0.05, 914 cases are needed to be studied. Considering the detection rate of 80% of SLNs, a
      total of 1143 cases are expected to be studied.

      C. Statistical Analysis Methods General principle Using a two-sided test, a P value of less
      than 0.05 would be considered statistically significant.

      The quantitative indicators will calculate the mean, standard deviation, median, minimum,
      maximum, lower quartile (Q1), upper quartile (Q3), and the classification indicators will
      describe the number of cases and percentages.

      Comparison of clinicopathological features (age, body mass index, pathological type, tumor
      stage, grading, maximum tumor diameter, invasive myometrial depth, lymphatic vascular
      infiltration, and tracer method) for SLNs and undetected SLNs will be based on the type of
      indicator. For the comparison of quantitative data between groups, the t-test or Wilcoxon
      rank sum test will be used according to the data distribution. For the comparison of
      categorical data between groups, the data will be analyzed by chi-square test or exact
      probability method (if the chi-square test is not applicable). And the grade data was
      analyzed by Wilcoxon rank sum test or CMH test.

      Clinical diagnostic index calculation According to the true positive (TP), false negative
      (FN), true negative (TN), and false positive (FP), the results of SLNs pathological
      examination and all lymph node pathological examination results will be compared. The
      comparison results will be plotted as a four-grid table to calculate sensitivity, false
      negative rate, and negative predictive value, respectively.

      Chi-square test or exact probability method (if the chi-square test is not applicable) will
      be used to compare the clinical diagnosis value of SLNs biopsy of endometrial cancer patients
      with injection of carbon nanoparticles (CNP) or combined injection of CNP and indocyanine
      green(ICG).

      Chi-square test or exact probability method (if the chi-square test is not applicable) will
      be used to analyze the clinic-pathological factors affecting the detection rate of SLNs.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: The procedure is listed as follows:
Recruiting early stage cervical cancer patients undergoing extra-fascial/sub-extensive/extensive hysterectomy, pelvic with or without aortic lymph node resection from July 2018 to June 2020.
Selecting the Standard-compliant patients according to the inclusion and exclusion criteria.
Numbering the above patients and collecting their clinical data.
Injecting carbon nanoparticles (CNP)[Not Equipped with near-infrared fluorescent vascular imager] or CNP combining Indocyanine Green(ICG)[Equipped with near-infrared fluorescent vascular imager].
Identifying and removing sentinel lymph nodes.
Completing the total hysterectomy, biadnexectomy and pelvic with or without para-aortic lymphadenectomy.
Staining all nodes using hematoxylin-eosin staining.
Calculating the sensitivity, negative predictive value, etc.
primary purpose: Diagnostic
masking: None (Open Label)
measure: Negative Predictive Value
time frame: Through study completion, an average of 2 years
description: Sentinel lymph node detection is defined as at least one lymph node is found in a patient. Sentinel lymph node negative is defined as no sentinel lymph node detected. True negative is defined as no metastasis found in both sentinel lymph nodes (SLNs) and non-SLNs. Negative predictive value is defined as the proportion of true negative patients to SLNs negative patients in patients with sentinel lymph nodes detected, which means patients without SLNs detected won't be included in the calculation.
measure: SLNs detection rate
time frame: Through study completion, an average of 2 years
description: Sentinel lymph node detection is defined as at least one lymph node is found in a patient. The detection rate is the proportion of the patients with SLNs detected in all enrolled patients.
measure: Sensitivity
time frame: Through study completion, an average of 2 years
description: Sensitivity is defined as the proportion of the SLNs positive patients in patients with SLNs or non-SLNs lymphatic metastasis (among the patients with SLNs detected)
measure: False negative rate
time frame: Through study completion, an average of 2 years
description: False negative is defined as no metastasis found in SLNs while metastasis found in non-SLNs. False negative rate is defined as the proportion of the false negative patients in the patients with SLNs or non-SLNs lymphatic metastasis(among the patients with SLNs detected)
arm group label: Undergoing sentinel lymph node biopsy
arm group type: Experimental
description: This group of patients will undergo sentinel lymph node biopsy.
intervention type: Procedure
intervention name: sentinel lymph node biopsy
description: Injecting carbon nanoparticles (CNP)[Not Equipped with near-infrared fluorescent vascular imager] or CNP combining Indocyanine Green(ICG)[Equipped with near-infrared fluorescent vascular imager].
Identifying and removing sentinel lymph nodes.
Staining all nodes using hematoxylin-eosin staining.
arm group label: Undergoing sentinel lymph node biopsy
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Jianliu Wang, Professor
role: Study Director
affiliation: Peking University People's Hospital
last name: Jianliu Wang, Professor
phone: 88324385
phone ext: 010
email: wangjianliu@pku.edu.cn
facility: 
status: Recruiting
contact: 
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status: Recruiting
country: China
citation: Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015 Mar 1;136(5):E359-86. doi: 10.1002/ijc.29210. Epub 2014 Oct 9.
PMID: 25220842
citation: Creasman WT, Morrow CP, Bundy BN, Homesley HD, Graham JE, Heller PB. Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study. Cancer. 1987 Oct 15;60(8 Suppl):2035-41. doi: 10.1002/1097-0142(19901015)60:8+3.0.co;2-8.
PMID: 3652025
citation: NCCN Guidelines Version 1. 2018. Cervical Cancer [EB/OL]. [2018-02-10]. http://www.nccn.org/professionals/physician_gls/pdf/cervical.pdf.
citation: Lu Y, Wei JY, Yao DS, Pan ZM, Yao Y. Application of carbon nanoparticles in laparoscopic sentinel lymph node detection in patients with early-stage cervical cancer. PLoS One. 2017 Sep 5;12(9):e0183834. doi: 10.1371/journal.pone.0183834. eCollection 2017.
PMID: 28873443
citation: Holloway RW, Abu-Rustum NR, Backes FJ, Boggess JF, Gotlieb WH, Jeffrey Lowery W, Rossi EC, Tanner EJ, Wolsky RJ. Sentinel lymph node mapping and staging in endometrial cancer: A Society of Gynecologic Oncology literature review with consensus recommendations. Gynecol Oncol. 2017 Aug;146(2):405-415. doi: 10.1016/j.ygyno.2017.05.027. Epub 2017 May 28.
PMID: 28566221
citation: Liang SC, Wang ZQ, Wang JL. [Clinical analysis of 76 cases of sentinel lymph node detection in cervical cancer and endometrial cancer]. Zhonghua Fu Chan Ke Za Zhi. 2017 Sep 25;52(9):605-611. doi: 10.3760/cma.j.issn.0529-567X.2017.09.006. Chinese.
PMID: 28954449
responsible party type: Sponsor
mesh term: Uterine Cervical Neoplasms
sharing ipd: Yes
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)