<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/NCT01730651</url>
  </required_header>
  <id_info>
    <org_study_id>NCCCTS 12-615</org_study_id>
    <nct_id>NCT01730651</nct_id>
  </id_info>
  <brief_title>High Dose Intensity Modulated Radiation Therapy in the Cervical Cancer With Metastatic Lymphadenopathies.</brief_title>
  <official_title>A Phase II Study of High Dose Intensity Modulated Radiation Therapy in the Cervical Cancer With Metastatic Lymphadenopathies at Initial Diagnosis.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Center, Korea</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Keimyung University Dongsan Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>National Cancer Center, Korea</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II study of high dose intensity modulated radiation therapy in the cervical cancer&#xD;
      with metastatic lymphadenopathies at initial diagnosis&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Lymph node (LN) involvement in cervical cancer is a poor prognostic factor(1). Although lymph&#xD;
      node evaluation is not a part of the International Federation of Gynecology and Obstetrics&#xD;
      (FIGO) staging system(2), it is generally performed as one of the initial workup of patients&#xD;
      with cervical cancer by use of modern imaging tools for accurate evaluation of the disease&#xD;
      extent and possible treatment adjustment. Kidd et al reported the positron emission&#xD;
      tomography with [18F] fluorodeoxyglucose (FDG-PET)-positive lymph node rate is 47% at&#xD;
      diagnosis in 560 patients. They also showed that within a stage, patients with PET-positive&#xD;
      lymph nodes had significantly worse disease specific survival than those with PET-negative&#xD;
      lymph nodes (p&lt;0.001)(3).&#xD;
&#xD;
      Historically, dose escalation to the pelvic or para-aortic metastatic lymphadenopathies was&#xD;
      not given as much attention as primary uterine cervical lesion partly because of the expected&#xD;
      increased risk of bowel toxicity with when conventional radiotherapy technique was used.&#xD;
      Unlike for the head and neck cancer where intensity modulated radiation therapy (IMRT) or&#xD;
      tomotherapy was actively used for treatment of large lymphadenopathies and shown to produce&#xD;
      improved disease control(4, 5) , there are few similar studies for cervical cancer. It is&#xD;
      well known that more than 60 Gy10 2Gy equivalent dose (EQD2, α/β=10 Gy) is needed to control&#xD;
      the gross tumor sized of 10 mm, containing 109 cells, according to the logarithmic cell&#xD;
      killing(6). Theoretically, pelvic and para-aortic LNs (PAN) could not be controlled with the&#xD;
      dose of 45-50 Gy10 EQD2, and we need to escalate the dose as much as possible with new&#xD;
      radiation technology.&#xD;
&#xD;
      In the current is study, we evaluate the LNs control rate, toxicity rate, progression-free&#xD;
      survival and overall survival in cervical cancer patients with lymphadenopathies and treated&#xD;
      with high dose intensity modulated radiation therapy&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">July 13, 2012</start_date>
  <completion_date type="Anticipated">July 2022</completion_date>
  <primary_completion_date type="Anticipated">July 2022</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall survival</measure>
    <time_frame>documented data of death, up to 3 years</time_frame>
    <description>From date of initiation of radiotherapy until the date of documented date of death from any cause, assessed up to 3 years</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease-free survival (DFS)</measure>
    <time_frame>documented date of progression or death, up to 3 years</time_frame>
    <description>From date of initiation of radiotherapy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years.&#xD;
Progression-free survival of lymph nodes(LNs) treated with high dose ② Regional LN (other than the LNs treated with high dose) failure-free survival ③ Distant organ (other than para-aortic LNs[PAN]) failure-free survival</description>
  </secondary_outcome>
  <other_outcome>
    <measure>RTOG acute and late Toxicity</measure>
    <time_frame>every follow-up date, up to 3 years</time_frame>
    <description>① Acute: gastrointestinal (GI), genitourinary (GU), bone marrow (BM)&#xD;
② Late: GI, GU, lower extremity edema, treatment-related neuropathy, bone density change</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">55</enrollment>
  <condition>Cervical Cancer</condition>
  <arm_group>
    <arm_group_label>Tomotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tomotherapy fraction size (Gy) = 0.4 x 진단 당시의 LN short diameter (cm) + 1.6 (pilot study range, 1.5-3.0 Gy)&#xD;
Total dose(summation dose with 3D-CRT) (Gy10) (EQD2, α/β=10 Gy) = 5 x 진단 당시의 LN short diameter (cm) + 56 (pilot study range, 54.6-78.0 Gy)</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Tomotherapy</intervention_name>
    <description>IMRT boost of gross LNs&#xD;
Tomotherapy fraction size (Gy) = 0.4 x 진단 당시의 LN short diameter (cm) + 1.6 (pilot study range, 1.5-3.0 Gy)&#xD;
Total dose(summation dose with 3D-CRT) (Gy10) (EQD2, α/β=10 Gy) = 5 x 진단 당시의 LN short diameter (cm) + 56 (pilot study range, 54.6-78.0 Gy)</description>
    <arm_group_label>Tomotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients (who have been adequately clinically staged) with primary, untreated,&#xD;
             histologically confirmed carcinoma of the uterine cervix (including clear cell and&#xD;
             small cell carcinoma), with metastatic lymphadenopathies (any of pelvis or PAN &gt;1.5 cm&#xD;
             in short diameter, with/without biopsy proven inguinal lymph node [ING])&#xD;
&#xD;
          2. Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, 2&#xD;
&#xD;
          3. Patients with adequate bone marrow function: absolute neutrophil count (ANC) greater&#xD;
             than or equal to 1,500/mcl, platelets greater than or equal to 100,000/mcl at the&#xD;
             beginning.&#xD;
&#xD;
          4. Patients with adequate renal function: creatinine equal to or less than 2.0 mg%.&#xD;
&#xD;
          5. Patients who have signed an approved informed consent and authorization&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with recurrent LN(s) which was(were) previously irradiated.&#xD;
&#xD;
          2. Patients who have diagnosis of other malignance tumors except papillary or follicular&#xD;
             thyroid cancer or skin cancer&#xD;
&#xD;
          3. Patients with metastatic lymphadenopathies other than pelvis, PAN, ING (e.g.&#xD;
             supraclavicular or mediastinal metastatic lymphadenopathy)&#xD;
&#xD;
          4. Patients with distant organ metastasis (e.g. bone, lung, brain…)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jooyoung Kim, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Cancer Center, Korea</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Cancer Center</name>
      <address>
        <city>Goyang-si,</city>
        <state>Gyeonggi-do</state>
        <zip>411-769</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Center, Korea</name>
      <address>
        <city>Goyang-si</city>
        <state>Gyeonggi-do</state>
        <zip>410-769</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>October 15, 2012</study_first_submitted>
  <study_first_submitted_qc>November 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2012</study_first_posted>
  <last_update_submitted>September 14, 2020</last_update_submitted>
  <last_update_submitted_qc>September 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National Cancer Center, Korea</investigator_affiliation>
    <investigator_full_name>Joo-Young Kim</investigator_full_name>
    <investigator_title>PI</investigator_title>
  </responsible_party>
  <keyword>cervical cancer with metastatic lymphadenopathies</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Uterine Cervical Neoplasms</mesh_term>
    <mesh_term>Lymphadenopathy</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>undecided</ipd_description>
  </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/NCT01730651
org study id: NCCCTS 12-615
nct id: NCT01730651
lead sponsor: 
collaborator: 
has dmc: Yes
This phase II study of high dose intensity modulated radiation therapy in the cervical cancer
      with metastatic lymphadenopathies at initial diagnosis
Lymph node (LN) involvement in cervical cancer is a poor prognostic factor(1). Although lymph
      node evaluation is not a part of the International Federation of Gynecology and Obstetrics
      (FIGO) staging system(2), it is generally performed as one of the initial workup of patients
      with cervical cancer by use of modern imaging tools for accurate evaluation of the disease
      extent and possible treatment adjustment. Kidd et al reported the positron emission
      tomography with [18F] fluorodeoxyglucose (FDG-PET)-positive lymph node rate is 47% at
      diagnosis in 560 patients. They also showed that within a stage, patients with PET-positive
      lymph nodes had significantly worse disease specific survival than those with PET-negative
      lymph nodes (p<0.001)(3).

      Historically, dose escalation to the pelvic or para-aortic metastatic lymphadenopathies was
      not given as much attention as primary uterine cervical lesion partly because of the expected
      increased risk of bowel toxicity with when conventional radiotherapy technique was used.
      Unlike for the head and neck cancer where intensity modulated radiation therapy (IMRT) or
      tomotherapy was actively used for treatment of large lymphadenopathies and shown to produce
      improved disease control(4, 5) , there are few similar studies for cervical cancer. It is
      well known that more than 60 Gy10 2Gy equivalent dose (EQD2, α/β=10 Gy) is needed to control
      the gross tumor sized of 10 mm, containing 109 cells, according to the logarithmic cell
      killing(6). Theoretically, pelvic and para-aortic LNs (PAN) could not be controlled with the
      dose of 45-50 Gy10 EQD2, and we need to escalate the dose as much as possible with new
      radiation technology.

      In the current is study, we evaluate the LNs control rate, toxicity rate, progression-free
      survival and overall survival in cervical cancer patients with lymphadenopathies and treated
      with high dose intensity modulated radiation therapy
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall survival
time frame: documented data of death, up to 3 years
description: From date of initiation of radiotherapy until the date of documented date of death from any cause, assessed up to 3 years
measure: Disease-free survival (DFS)
time frame: documented date of progression or death, up to 3 years
description: From date of initiation of radiotherapy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years.
Progression-free survival of lymph nodes(LNs) treated with high dose ② Regional LN (other than the LNs treated with high dose) failure-free survival ③ Distant organ (other than para-aortic LNs[PAN]) failure-free survival
measure: RTOG acute and late Toxicity
time frame: every follow-up date, up to 3 years
description: ① Acute: gastrointestinal (GI), genitourinary (GU), bone marrow (BM)
② Late: GI, GU, lower extremity edema, treatment-related neuropathy, bone density change
arm group label: Tomotherapy
arm group type: Experimental
description: Tomotherapy fraction size (Gy) = 0.4 x 진단 당시의 LN short diameter (cm) + 1.6 (pilot study range, 1.5-3.0 Gy)
Total dose(summation dose with 3D-CRT) (Gy10) (EQD2, α/β=10 Gy) = 5 x 진단 당시의 LN short diameter (cm) + 56 (pilot study range, 54.6-78.0 Gy)
intervention type: Radiation
intervention name: Tomotherapy
description: IMRT boost of gross LNs
Tomotherapy fraction size (Gy) = 0.4 x 진단 당시의 LN short diameter (cm) + 1.6 (pilot study range, 1.5-3.0 Gy)
Total dose(summation dose with 3D-CRT) (Gy10) (EQD2, α/β=10 Gy) = 5 x 진단 당시의 LN short diameter (cm) + 56 (pilot study range, 54.6-78.0 Gy)
arm group label: Tomotherapy
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jooyoung Kim, M.D.
role: Principal Investigator
affiliation: National Cancer Center, Korea
facility: 
facility: 
country: Korea, Republic of
responsible party type: Principal Investigator
investigator affiliation: National Cancer Center, Korea
investigator full name: Joo-Young Kim
investigator title: PI
mesh term: Uterine Cervical Neoplasms
mesh term: Lymphadenopathy
sharing ipd: Undecided
ipd description: undecided