<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/NCT03257475</url>
  </required_header>
  <id_info>
    <org_study_id>XIAN J</org_study_id>
    <nct_id>NCT03257475</nct_id>
  </id_info>
  <brief_title>Evaluation of Vaginal Dose in Cervical Cancer Patients Treated With Radiotherapy</brief_title>
  <official_title>Evaluation of Vaginal Dose in Cervical Cancer Patients Treated With Radiotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Health Science Center of Xi'an Jiaotong University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Health Science Center of Xi'an Jiaotong University</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>
      Cervical cancer is the most common malignant in women with the average five-year overall&#xD;
      survival rate as high as 70%. Radiation therapy is the main treatment for cervical cancer.&#xD;
      Vagina is one of the important organ at risk and also a target organ in the treatment of&#xD;
      cervical cancer patients. Vaginal radiation has serious related complications that affect the&#xD;
      quality of life of patients and therefore needs much clinical attention. But due to lack of&#xD;
      sufficient evidence, the clinical dose to the vagina is limited. ICRU-89 defined the&#xD;
      recto-vaginal reference point (R-V) as a reference point for vaginal dose assessment.&#xD;
      However, the R-V position is affected by applicator placement, vaginal packing and other&#xD;
      factors hence the dose point only do not represent the entire vaginal radiation dose&#xD;
      resulting in some clinical limitations. The latest research in Europe proposed that&#xD;
      PIBS(Posterior-Inferior Border of Symphysis) / PIBS ± 2cm and VRL (vaginal reference length)&#xD;
      may be more reasonable to use to assess vagina radiation doses, but it remains to be further&#xD;
      clinically investigated. Therefore, this study intends to perform radical radiotherapy in&#xD;
      cervical cancer patients and also by recruiting local and foreign hospitals into this study&#xD;
      by recording its PIBS/ PIBS ± 2cm, VRL, R-V point dose, acute and chronic radiation injury&#xD;
      incidence of vagina and other useful data. T-test and chi-square will be used to compare the&#xD;
      data between Asian and European women. Correlation analysis will be used to determine if&#xD;
      there is a relation between R-V and PIBS point dose. Furthermore, logic and or COX regression&#xD;
      model to evaluate PIBS / PIBS ± 2cm and R-V point doses of vaginal radiation injury&#xD;
      relationships, while exploring other relevant factors causing vaginal radiation injury. This&#xD;
      is eventually expected to provide a scientific, simple and reliable reference point for&#xD;
      vaginal dose assessment and clinical dose limit.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. a detailed record of the irradiation dose and R-V point dose for all patients PIBS /&#xD;
           PIBS ± 2cm, VRL data were taken.&#xD;
&#xD;
        2. according to CTCAE v3.0 standard, accurate and detailed record of patient treatment,&#xD;
           after treatment of 2 years and the incidence of vaginal complications were recorded.&#xD;
&#xD;
        3. COX regression model was used to find dose-effect relationship between the reference&#xD;
           point and vaginal complications.&#xD;
&#xD;
      Clinical Scheme:&#xD;
&#xD;
      Inclusion criteria: Pathologically confirmed cervical cancer patients, FIGO stage ⅠA- ⅣA&#xD;
      patients who underwent radical radiotherapy, Any pathological type&#xD;
&#xD;
      Exclusion criteria: FIGO staging of cervical cancer ⅢA; Age &gt; 60 years due to vaginal&#xD;
      stenosis during the treatment course&#xD;
&#xD;
        1. pre-treatment: Abdominal and Chest CT scan before treatment. Patients were given pelvic&#xD;
           MRI after EBRT to measure VRL before the start of brachytherapy.&#xD;
&#xD;
        2. 3DCRT / IMRT was used and according to RTOG target outlined recommendation dose of&#xD;
           46-50Gy / 23-25f; recording PIBS WP and R-V WP dose.&#xD;
&#xD;
        3. Intracavitary irradiation starts at the end of the external beam radiation using&#xD;
           image-guided CT / SIM. catheterization of full bladder. Patients were advice to have&#xD;
           empty rectum before CT scan&#xD;
&#xD;
           The first treatment method:&#xD;
&#xD;
             1. Catheterization: placement of catheter inside bladder and injection of contrast&#xD;
                agent-containing 7ml liquid&#xD;
&#xD;
             2. Place uterine and vaginal applicator device (must double the bulb), vaginal&#xD;
                orifices ball from 3cm, and record&#xD;
&#xD;
             3. Vaginal packing with gauze is done to keep the applicator fixed.&#xD;
&#xD;
             4. Barium into the rectum and anal canal.&#xD;
&#xD;
             5. CT/SIM (transverse axis) is done to complete 3D / 2D treatment planning.&#xD;
                measurement VRL, PIBS and PIBS ± 2cm, R-V were recorded;&#xD;
&#xD;
             6. Brachytherapy plan: Point A: 24-30Gy / 4-5f, or 21-28Gy / 3-4f HR-CTV: ≥85Gy,&#xD;
                IR-CTV 65Gy dose records;&#xD;
&#xD;
        4. Concurrent chemotherapy: DDP 30-40mg / m2 * 5w or T 135mg / m2D1 + DDP 30mg / m2 d1-3;&#xD;
&#xD;
        5. vaginal washing method is every day from the beginning of radiation therapy for six&#xD;
           months. After 6 months, it was done twice per week for 2 years.&#xD;
&#xD;
        6. vaginal radiation complications were recorded according to CTCAE 3.0 standard&#xD;
&#xD;
        7. Gynecological examination and MRI was performed before radiotherapy and brachytherapy&#xD;
           treatment and also after the entire treatment period. Patients follow-up was done on the&#xD;
           1,3,6,9,12,18 and 24th month after treatment during which vaginal radiation complication&#xD;
           were evaluated according to CTCAE 3.0 standard&#xD;
&#xD;
        8. COX regression model was used to find dose-effect relationship between the reference&#xD;
           point and vaginal complications.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">March 1, 2017</start_date>
  <completion_date type="Anticipated">August 30, 2019</completion_date>
  <primary_completion_date type="Anticipated">February 28, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>PIBS/PIBS±2cm dose in Gy</measure>
    <time_frame>two weeks</time_frame>
    <description>record the PIBS/PIBS±2cm dose by planning system</description>
  </primary_outcome>
  <primary_outcome>
    <measure>VRL in centimeter</measure>
    <time_frame>two weeks</time_frame>
    <description>measure the VRL in MRI</description>
  </primary_outcome>
  <primary_outcome>
    <measure>R-V dose in Gy</measure>
    <time_frame>two weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>acute and chronic radiation injury incidence of vagina</measure>
    <time_frame>two years</time_frame>
    <description>acute and chronic radiation injury incidence of vaginaas assessed by CTCAE v4.0</description>
  </primary_outcome>
  <enrollment type="Anticipated">500</enrollment>
  <condition>Cervical Cancer</condition>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Brachytherapy</intervention_name>
    <description>Intracavitary irradiation starts at the end of the external beam radiation using image-guided CT/SIM.CT/SIM (transverse axis) is done to complete 3/2D treatment planning. Measurement VRL, PIBS and PIBS ± 2cm, R-V were recorded; Brachytherapy plan: Point A: 24-30Gy/4-5f, or 21-28Gy/3-4f HR-CTV: ≥85Gy, IR-CTV 65Gy dose records</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Pathologically confirmed cervical cancer patients, FIGO stage ⅠA-ⅣA patients who underwent&#xD;
        radical radiotherapy except ⅢA, Any pathological type.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pathologically confirmed cervical cancer patients;&#xD;
&#xD;
          -  FIGO stage ⅠA- ⅣA patients who underwent radical radiotherapy;&#xD;
&#xD;
          -  Any pathological type&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  FIGO staging of cervical cancer ⅢA;&#xD;
&#xD;
          -  Age &gt; 60 years&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Juan Wang, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>First Affiliated Hospital Xi'an Jiaotong University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The First Affiliated Hospital of Xi'an Jiao Tong University</name>
      <address>
        <city>Xi'an</city>
        <state>Shaanxi</state>
        <zip>710061</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Fidarova EF, Berger D, Schussler S, Dimopoulos J, Kirisits C, Georg P, Bachtiary B, Potter R. Dose volume parameter D2cc does not correlate with vaginal side effects in individual patients with cervical cancer treated within a defined treatment protocol with very high brachytherapy doses. Radiother Oncol. 2010 Oct;97(1):76-9. doi: 10.1016/j.radonc.2010.05.005. Epub 2010 Jun 17.</citation>
    <PMID>20561694</PMID>
  </reference>
  <reference>
    <citation>Rai B, Dhanireddy B, Patel FD, Kumari R, Oinam AS, Simha V, Sharma S. Vaginal dose, toxicity and sexual outcomes in patients of cervical cancer undergoing image based brachytherapy. Asian Pac J Cancer Prev. 2014;15(8):3619-23. doi: 10.7314/apjcp.2014.15.8.3619.</citation>
    <PMID>24870767</PMID>
  </reference>
  <reference>
    <citation>Murakami N, Kasamatsu T, Sumi M, Yoshimura R, Harada K, Kitaguchi M, Sekii S, Takahashi K, Yoshio K, Inaba K, Morota M, Ito Y, Itami J. Vaginal tolerance of CT based image-guided high-dose rate interstitial brachytherapy for gynecological malignancies. Radiat Oncol. 2014 Jan 23;9:31. doi: 10.1186/1748-717X-9-31.</citation>
    <PMID>24456669</PMID>
  </reference>
  <reference>
    <citation>Prescribing, Recording, and Reporting Brachytherapy for Cancer of the Cervix. J ICRU. 2013 Apr;13(1-2):NP. doi: 10.1093/jicru/ndw027. No abstract available.</citation>
    <PMID>27335496</PMID>
  </reference>
  <reference>
    <citation>Kirchheiner K, Nout RA, Lindegaard JC, Haie-Meder C, Mahantshetty U, Segedin B, Jurgenliemk-Schulz IM, Hoskin PJ, Rai B, Dorr W, Kirisits C, Bentzen SM, Potter R, Tanderup K; EMBRACE Collaborative Group. Dose-effect relationship and risk factors for vaginal stenosis after definitive radio(chemo)therapy with image-guided brachytherapy for locally advanced cervical cancer in the EMBRACE study. Radiother Oncol. 2016 Jan;118(1):160-6. doi: 10.1016/j.radonc.2015.12.025. Epub 2016 Jan 9.</citation>
    <PMID>26780997</PMID>
  </reference>
  <reference>
    <citation>Susko M, Craciunescu O, Meltsner S, Yang Y, Steffey B, Cai J, Chino J. Vaginal Dose Is Associated With Toxicity in Image Guided Tandem Ring or Ovoid-Based Brachytherapy. Int J Radiat Oncol Biol Phys. 2016 Apr 1;94(5):1099-105. doi: 10.1016/j.ijrobp.2015.12.360. Epub 2015 Dec 19.</citation>
    <PMID>26883564</PMID>
  </reference>
  <reference>
    <citation>Westerveld H, de Leeuw A, Kirchheiner K, Dankulchai P, Oosterveld B, Oinam A, Hudej R, Swamidas J, Lindegaard J, Tanderup K, Potter R, Kirisits C; EMBRACE Collaborative Group. Multicentre evaluation of a novel vaginal dose reporting method in 153 cervical cancer patients. Radiother Oncol. 2016 Sep;120(3):420-427. doi: 10.1016/j.radonc.2016.05.002. Epub 2016 May 26.</citation>
    <PMID>27237058</PMID>
  </reference>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 14, 2017</study_first_submitted>
  <study_first_submitted_qc>August 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 22, 2017</study_first_posted>
  <last_update_submitted>August 21, 2017</last_update_submitted>
  <last_update_submitted_qc>August 21, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 22, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Health Science Center of Xi'an Jiaotong University</investigator_affiliation>
    <investigator_full_name>Liu Zi</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>cervical cance</keyword>
  <keyword>vaginal radiation injury</keyword>
  <keyword>PIBS</keyword>
  <keyword>R-V</keyword>
  <keyword>VRL</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>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/NCT03257475
org study id: XIAN J
nct id: NCT03257475
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Cervical cancer is the most common malignant in women with the average five-year overall
      survival rate as high as 70%. Radiation therapy is the main treatment for cervical cancer.
      Vagina is one of the important organ at risk and also a target organ in the treatment of
      cervical cancer patients. Vaginal radiation has serious related complications that affect the
      quality of life of patients and therefore needs much clinical attention. But due to lack of
      sufficient evidence, the clinical dose to the vagina is limited. ICRU-89 defined the
      recto-vaginal reference point (R-V) as a reference point for vaginal dose assessment.
      However, the R-V position is affected by applicator placement, vaginal packing and other
      factors hence the dose point only do not represent the entire vaginal radiation dose
      resulting in some clinical limitations. The latest research in Europe proposed that
      PIBS(Posterior-Inferior Border of Symphysis) / PIBS ± 2cm and VRL (vaginal reference length)
      may be more reasonable to use to assess vagina radiation doses, but it remains to be further
      clinically investigated. Therefore, this study intends to perform radical radiotherapy in
      cervical cancer patients and also by recruiting local and foreign hospitals into this study
      by recording its PIBS/ PIBS ± 2cm, VRL, R-V point dose, acute and chronic radiation injury
      incidence of vagina and other useful data. T-test and chi-square will be used to compare the
      data between Asian and European women. Correlation analysis will be used to determine if
      there is a relation between R-V and PIBS point dose. Furthermore, logic and or COX regression
      model to evaluate PIBS / PIBS ± 2cm and R-V point doses of vaginal radiation injury
      relationships, while exploring other relevant factors causing vaginal radiation injury. This
      is eventually expected to provide a scientific, simple and reliable reference point for
      vaginal dose assessment and clinical dose limit.
1. a detailed record of the irradiation dose and R-V point dose for all patients PIBS /
           PIBS ± 2cm, VRL data were taken.

        2. according to CTCAE v3.0 standard, accurate and detailed record of patient treatment,
           after treatment of 2 years and the incidence of vaginal complications were recorded.

        3. COX regression model was used to find dose-effect relationship between the reference
           point and vaginal complications.

      Clinical Scheme:

      Inclusion criteria: Pathologically confirmed cervical cancer patients, FIGO stage ⅠA- ⅣA
      patients who underwent radical radiotherapy, Any pathological type

      Exclusion criteria: FIGO staging of cervical cancer ⅢA; Age > 60 years due to vaginal
      stenosis during the treatment course

        1. pre-treatment: Abdominal and Chest CT scan before treatment. Patients were given pelvic
           MRI after EBRT to measure VRL before the start of brachytherapy.

        2. 3DCRT / IMRT was used and according to RTOG target outlined recommendation dose of
           46-50Gy / 23-25f; recording PIBS WP and R-V WP dose.

        3. Intracavitary irradiation starts at the end of the external beam radiation using
           image-guided CT / SIM. catheterization of full bladder. Patients were advice to have
           empty rectum before CT scan

           The first treatment method:

             1. Catheterization: placement of catheter inside bladder and injection of contrast
                agent-containing 7ml liquid

             2. Place uterine and vaginal applicator device (must double the bulb), vaginal
                orifices ball from 3cm, and record

             3. Vaginal packing with gauze is done to keep the applicator fixed.

             4. Barium into the rectum and anal canal.

             5. CT/SIM (transverse axis) is done to complete 3D / 2D treatment planning.
                measurement VRL, PIBS and PIBS ± 2cm, R-V were recorded;

             6. Brachytherapy plan: Point A: 24-30Gy / 4-5f, or 21-28Gy / 3-4f HR-CTV: ≥85Gy,
                IR-CTV 65Gy dose records;

        4. Concurrent chemotherapy: DDP 30-40mg / m2 * 5w or T 135mg / m2D1 + DDP 30mg / m2 d1-3;

        5. vaginal washing method is every day from the beginning of radiation therapy for six
           months. After 6 months, it was done twice per week for 2 years.

        6. vaginal radiation complications were recorded according to CTCAE 3.0 standard

        7. Gynecological examination and MRI was performed before radiotherapy and brachytherapy
           treatment and also after the entire treatment period. Patients follow-up was done on the
           1,3,6,9,12,18 and 24th month after treatment during which vaginal radiation complication
           were evaluated according to CTCAE 3.0 standard

        8. COX regression model was used to find dose-effect relationship between the reference
           point and vaginal complications.
observational model: Case-Only
time perspective: Prospective
measure: PIBS/PIBS±2cm dose in Gy
time frame: two weeks
description: record the PIBS/PIBS±2cm dose by planning system
measure: VRL in centimeter
time frame: two weeks
description: measure the VRL in MRI
measure: R-V dose in Gy
time frame: two weeks
measure: acute and chronic radiation injury incidence of vagina
time frame: two years
description: acute and chronic radiation injury incidence of vaginaas assessed by CTCAE v4.0
intervention type: Radiation
intervention name: Brachytherapy
description: Intracavitary irradiation starts at the end of the external beam radiation using image-guided CT/SIM.CT/SIM (transverse axis) is done to complete 3/2D treatment planning. Measurement VRL, PIBS and PIBS ± 2cm, R-V were recorded; Brachytherapy plan: Point A: 24-30Gy/4-5f, or 21-28Gy/3-4f HR-CTV: ≥85Gy, IR-CTV 65Gy dose records
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: N/A
maximum age: 60 Years
healthy volunteers: No
last name: Juan Wang, Ph.D
role: Principal Investigator
affiliation: First Affiliated Hospital Xi'an Jiaotong University
facility: 
country: China
citation: Fidarova EF, Berger D, Schussler S, Dimopoulos J, Kirisits C, Georg P, Bachtiary B, Potter R. Dose volume parameter D2cc does not correlate with vaginal side effects in individual patients with cervical cancer treated within a defined treatment protocol with very high brachytherapy doses. Radiother Oncol. 2010 Oct;97(1):76-9. doi: 10.1016/j.radonc.2010.05.005. Epub 2010 Jun 17.
PMID: 20561694
citation: Rai B, Dhanireddy B, Patel FD, Kumari R, Oinam AS, Simha V, Sharma S. Vaginal dose, toxicity and sexual outcomes in patients of cervical cancer undergoing image based brachytherapy. Asian Pac J Cancer Prev. 2014;15(8):3619-23. doi: 10.7314/apjcp.2014.15.8.3619.
PMID: 24870767
citation: Murakami N, Kasamatsu T, Sumi M, Yoshimura R, Harada K, Kitaguchi M, Sekii S, Takahashi K, Yoshio K, Inaba K, Morota M, Ito Y, Itami J. Vaginal tolerance of CT based image-guided high-dose rate interstitial brachytherapy for gynecological malignancies. Radiat Oncol. 2014 Jan 23;9:31. doi: 10.1186/1748-717X-9-31.
PMID: 24456669
citation: Prescribing, Recording, and Reporting Brachytherapy for Cancer of the Cervix. J ICRU. 2013 Apr;13(1-2):NP. doi: 10.1093/jicru/ndw027. No abstract available.
PMID: 27335496
citation: Kirchheiner K, Nout RA, Lindegaard JC, Haie-Meder C, Mahantshetty U, Segedin B, Jurgenliemk-Schulz IM, Hoskin PJ, Rai B, Dorr W, Kirisits C, Bentzen SM, Potter R, Tanderup K; EMBRACE Collaborative Group. Dose-effect relationship and risk factors for vaginal stenosis after definitive radio(chemo)therapy with image-guided brachytherapy for locally advanced cervical cancer in the EMBRACE study. Radiother Oncol. 2016 Jan;118(1):160-6. doi: 10.1016/j.radonc.2015.12.025. Epub 2016 Jan 9.
PMID: 26780997
citation: Susko M, Craciunescu O, Meltsner S, Yang Y, Steffey B, Cai J, Chino J. Vaginal Dose Is Associated With Toxicity in Image Guided Tandem Ring or Ovoid-Based Brachytherapy. Int J Radiat Oncol Biol Phys. 2016 Apr 1;94(5):1099-105. doi: 10.1016/j.ijrobp.2015.12.360. Epub 2015 Dec 19.
PMID: 26883564
citation: Westerveld H, de Leeuw A, Kirchheiner K, Dankulchai P, Oosterveld B, Oinam A, Hudej R, Swamidas J, Lindegaard J, Tanderup K, Potter R, Kirisits C; EMBRACE Collaborative Group. Multicentre evaluation of a novel vaginal dose reporting method in 153 cervical cancer patients. Radiother Oncol. 2016 Sep;120(3):420-427. doi: 10.1016/j.radonc.2016.05.002. Epub 2016 May 26.
PMID: 27237058
responsible party type: Principal Investigator
investigator affiliation: Health Science Center of Xi'an Jiaotong University
investigator full name: Liu Zi
investigator title: Professor
mesh term: Uterine Cervical Neoplasms
sharing ipd: No