<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/NCT03040921</url>
  </required_header>
  <id_info>
    <org_study_id>HEG01</org_study_id>
    <nct_id>NCT03040921</nct_id>
  </id_info>
  <brief_title>Uterine Transposition: Feasibility Study</brief_title>
  <official_title>Uterine Transposition: Feasibility Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital Erasto Gaertner</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital Erasto Gaertner</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>
      This prospective nonrandomized multicenter phase I study, will evaluate the feasibility of&#xD;
      performing uterine transposition before chemoradiation for rectal cancer and uterine&#xD;
      reimplantation after the treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with pelvic cancer frequently require radiotherapy, which causes infertility even at&#xD;
      low doses. Oocytes are highly sensitive to radiation, as a dose of 2 Gy is able to destroy up&#xD;
      to 50% of the oocyte population.&#xD;
&#xD;
      Pelvic radiotherapy with fertility preservation is not yet available for women with pelvic&#xD;
      tumors. In such cases, the only options are egg and/or embryo freezing and ovarian&#xD;
      transposition (OT), which might preserve reproductive and hormonal function, respectively.&#xD;
      While ovarian tissue cryopreservation and transplantation are possible, they are still&#xD;
      experimental.&#xD;
&#xD;
      Uterine and adnexal transposition (UT) to the upper abdomen before radiotherapy might protect&#xD;
      these organs, and the later repositioning of the uterus into the pelvis after radiotherapy&#xD;
      might allow the patients to experience a normal pregnancy.&#xD;
&#xD;
      Methods:&#xD;
&#xD;
      Patients with pelvic cancer who will need pelvic radiation will be offered the possibility to&#xD;
      performed the uterine transposition before the radiation therapy and after the treatment the&#xD;
      uterus will be replaced in it's natural position. The study period is 2 years or 10 patients,&#xD;
      that happens first.&#xD;
&#xD;
      The suggested treatment consisted of oocyte or embryos vitrification or before the uterine&#xD;
      transposition, but this is not mandatory.&#xD;
&#xD;
      Patient preparation, equipment and trocars placement will be performed as usual for pelvis&#xD;
      procedures and retroperitoneal dissection. The following provides each step of the surgical&#xD;
      procedure: sealing and section of the round ligament; opening of the broad ligament;&#xD;
      dissection of the vesicovaginal space; sealing and section of the uterine vessels at the&#xD;
      level of the cervix; sealing and sectioning of the pericervical vessels and uterosacral&#xD;
      ligaments; Section of the vagina. Closure of the vagina with absorbable sutures; dissection&#xD;
      of the infundibulopelvic (IP) ligaments up to their intersection with the iliac vessels;&#xD;
      separation of the terminal ileum, right, sigmoid and descending colon from the&#xD;
      retroperitoneal space to allow dissection of the gonadal vessels up to their origin;&#xD;
      transposition of the uterus to the upper abdomen, and repositioning of the colon and ileum&#xD;
      bellow the arch formed by the uterus, adnexa and the corresponding vessels; fixation of the&#xD;
      round ligaments and gonadal vessels to the upper abdomen by means of a transparietal suture&#xD;
      to avoid herniation or by moving them into the pelvis; draining the pneumoperitoneum and&#xD;
      placement of transabdominal sutures at the site; fixation of the cervix to the umbilical&#xD;
      incision to allow for menstruation from the navel; and visual inspection of the cervix, which&#xD;
      indicates the end of the surgical procedure. The adnexa should not be contacted at any time&#xD;
      during surgery.&#xD;
&#xD;
      Postoperative care will be performed as for major procedures in gynecology. Visual inspection&#xD;
      of the cervix will be performed twice per day, and uterine perfusion was assessed every 2&#xD;
      days by Doppler ultrasound of the ovarian vessels. The patient is discharged 2-4 days after&#xD;
      surgery if no complications occur. Three-dimensional radiotherapy or Intensity-Modulated&#xD;
      Radiation Therapy following the standard treatment for the disease will start 10 to 14 days&#xD;
      later. Chemotherapy may be used, also following the usual treatment. Chemotherapy and&#xD;
      radiotherapy protocols must follow the standard treatment of the disease, no adaptations are&#xD;
      accepted.&#xD;
&#xD;
      Five weeks after the end of radiotherapy, in rectal cancer cases, rectosigmoidectomy with&#xD;
      total mesorectal excision (TME) and repositioning of the uterus will be performed. Patients&#xD;
      with other tumors that do not need surgery as part of its treatment, the uterine&#xD;
      repositioning will be performed 7 - 30 days after the end of the treatment.&#xD;
&#xD;
      The repositioning procedures is performed as follows: First, the cervix is separated from the&#xD;
      navel, and the first trocar is inserted. Second, adhesions are removed, and the uterus and&#xD;
      adnexa are repositioned into the pelvis. Rectosigmoidectomy with laparoscopic TME then&#xD;
      followed the usual technique., Chromotubation is performed at the end of the procedure to&#xD;
      demonstrate tubal patency. Patients without complications are expected to be discharged 2 - 4&#xD;
      days after surgery.&#xD;
&#xD;
      Seven days after surgery, cervical inspection is performed. Image exams will be performed as&#xD;
      clinically indicated in the postoperative period. Clinical evaluation with pelvic examination&#xD;
      will be performed every week for 4 weeks, then every months for 6 months and after that every&#xD;
      3 months for 2 years. Complications form will be filled in all clinical evaluations. Every 3&#xD;
      months, quality of life protocols will be applied. Abdominal and pelvic Magnetic resonance&#xD;
      will be performed 1, 6 and 12 months after the surgery. Transvaginal ultrasound will be&#xD;
      performed 2, 4 and 6 months after the surgery. Hormonal evaluation will be performed every 3&#xD;
      months. Tumor follow-up will be performed according to the institution protocols. It is&#xD;
      recommend to the patients to wait for 1 year before trying pregnancy.&#xD;
&#xD;
      Reports concerning safety will be presented every 6 months to the local Ethics Committee. No&#xD;
      uterine necrosis is expected and in case of 2 uterine necrosis, the study will be stoped. Up&#xD;
      to two local recurrences in the study period are accepted, but in case of a third recurrence,&#xD;
      the study will be stoped. All complication will be reviewed by the local board and the study&#xD;
      will be under permanent evaluation. Every 6 months the local board will provide a report&#xD;
      allowing the study to continue or not.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2017</start_date>
  <completion_date type="Actual">April 1, 2021</completion_date>
  <primary_completion_date type="Actual">June 1, 2019</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>Recruitment completed. Final data collection in April/2020.</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Uterine preservation after transposition to the upper abdomen and replacement in the pelvis</measure>
    <time_frame>6 months</time_frame>
    <description>The preservation of the uterus with normal endometrium confirmed by ultra-sound, after the surgery to place it in the upper abdomen and after replacing the uterus back to its normal position.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Morbidity</measure>
    <time_frame>6 months</time_frame>
    <description>Intraoperative and postoperative complications</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cancer recurrence</measure>
    <time_frame>Through study completion, an average of 2 years</time_frame>
    <description>Local and distant recurrences</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Postoperative Complications</condition>
  <condition>Intraoperative Complications</condition>
  <condition>Tissue Damage</condition>
  <condition>Ovarian Failure</condition>
  <condition>Uterus Disorder</condition>
  <arm_group>
    <arm_group_label>Uterine Transposition</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients submitted to uterine transposition.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Uterine transposition.</intervention_name>
    <description>Surgical transposition of the uterus to the upper abdomen. After the end of radiotherapy, rectosigmoidectomy is performed and the uterus is repositioned into the pelvis.</description>
    <arm_group_label>Uterine Transposition</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women with pelvic cancer and indication for pelvic radiation therapy who have&#xD;
             fertility sparing desire.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previously documented infertility, ovarian failure or gynecologic cancer.&#xD;
&#xD;
          -  More than 40 yo.&#xD;
&#xD;
          -  Previous oophorectomy&#xD;
&#xD;
          -  Tumor infiltrating uterus or adnexes&#xD;
&#xD;
          -  Presence of peritoneal metastasis&#xD;
&#xD;
          -  Presence of systemic metastasis&#xD;
&#xD;
          -  Previous retroperitoneal radiotherapy&#xD;
&#xD;
          -  Retroperitoneal radiotherapy planned&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Reitan Ribeiro, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Erasto Gaertner Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Erasto Gaertner Hospital</name>
      <address>
        <city>Curitiba</city>
        <state>Parana</state>
        <zip>81.520-060</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <link>
    <url>https://erastogaertner.com.br/</url>
    <description>Erasto Gaertner Hospital webpage</description>
  </link>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>January 14, 2017</study_first_submitted>
  <study_first_submitted_qc>January 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 2, 2017</study_first_posted>
  <last_update_submitted>January 8, 2022</last_update_submitted>
  <last_update_submitted_qc>January 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 11, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital Erasto Gaertner</investigator_affiliation>
    <investigator_full_name>Reitan Ribeiro</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Postoperative Complications</mesh_term>
    <mesh_term>Intraoperative Complications</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Hospital Ethics Committee did not approve individual participant data sharing. Recruitment completed. Final data collection in April/2020.</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/NCT03040921
org study id: HEG01
nct id: NCT03040921
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This prospective nonrandomized multicenter phase I study, will evaluate the feasibility of
      performing uterine transposition before chemoradiation for rectal cancer and uterine
      reimplantation after the treatment.
Patients with pelvic cancer frequently require radiotherapy, which causes infertility even at
      low doses. Oocytes are highly sensitive to radiation, as a dose of 2 Gy is able to destroy up
      to 50% of the oocyte population.

      Pelvic radiotherapy with fertility preservation is not yet available for women with pelvic
      tumors. In such cases, the only options are egg and/or embryo freezing and ovarian
      transposition (OT), which might preserve reproductive and hormonal function, respectively.
      While ovarian tissue cryopreservation and transplantation are possible, they are still
      experimental.

      Uterine and adnexal transposition (UT) to the upper abdomen before radiotherapy might protect
      these organs, and the later repositioning of the uterus into the pelvis after radiotherapy
      might allow the patients to experience a normal pregnancy.

      Methods:

      Patients with pelvic cancer who will need pelvic radiation will be offered the possibility to
      performed the uterine transposition before the radiation therapy and after the treatment the
      uterus will be replaced in it's natural position. The study period is 2 years or 10 patients,
      that happens first.

      The suggested treatment consisted of oocyte or embryos vitrification or before the uterine
      transposition, but this is not mandatory.

      Patient preparation, equipment and trocars placement will be performed as usual for pelvis
      procedures and retroperitoneal dissection. The following provides each step of the surgical
      procedure: sealing and section of the round ligament; opening of the broad ligament;
      dissection of the vesicovaginal space; sealing and section of the uterine vessels at the
      level of the cervix; sealing and sectioning of the pericervical vessels and uterosacral
      ligaments; Section of the vagina. Closure of the vagina with absorbable sutures; dissection
      of the infundibulopelvic (IP) ligaments up to their intersection with the iliac vessels;
      separation of the terminal ileum, right, sigmoid and descending colon from the
      retroperitoneal space to allow dissection of the gonadal vessels up to their origin;
      transposition of the uterus to the upper abdomen, and repositioning of the colon and ileum
      bellow the arch formed by the uterus, adnexa and the corresponding vessels; fixation of the
      round ligaments and gonadal vessels to the upper abdomen by means of a transparietal suture
      to avoid herniation or by moving them into the pelvis; draining the pneumoperitoneum and
      placement of transabdominal sutures at the site; fixation of the cervix to the umbilical
      incision to allow for menstruation from the navel; and visual inspection of the cervix, which
      indicates the end of the surgical procedure. The adnexa should not be contacted at any time
      during surgery.

      Postoperative care will be performed as for major procedures in gynecology. Visual inspection
      of the cervix will be performed twice per day, and uterine perfusion was assessed every 2
      days by Doppler ultrasound of the ovarian vessels. The patient is discharged 2-4 days after
      surgery if no complications occur. Three-dimensional radiotherapy or Intensity-Modulated
      Radiation Therapy following the standard treatment for the disease will start 10 to 14 days
      later. Chemotherapy may be used, also following the usual treatment. Chemotherapy and
      radiotherapy protocols must follow the standard treatment of the disease, no adaptations are
      accepted.

      Five weeks after the end of radiotherapy, in rectal cancer cases, rectosigmoidectomy with
      total mesorectal excision (TME) and repositioning of the uterus will be performed. Patients
      with other tumors that do not need surgery as part of its treatment, the uterine
      repositioning will be performed 7 - 30 days after the end of the treatment.

      The repositioning procedures is performed as follows: First, the cervix is separated from the
      navel, and the first trocar is inserted. Second, adhesions are removed, and the uterus and
      adnexa are repositioned into the pelvis. Rectosigmoidectomy with laparoscopic TME then
      followed the usual technique., Chromotubation is performed at the end of the procedure to
      demonstrate tubal patency. Patients without complications are expected to be discharged 2 - 4
      days after surgery.

      Seven days after surgery, cervical inspection is performed. Image exams will be performed as
      clinically indicated in the postoperative period. Clinical evaluation with pelvic examination
      will be performed every week for 4 weeks, then every months for 6 months and after that every
      3 months for 2 years. Complications form will be filled in all clinical evaluations. Every 3
      months, quality of life protocols will be applied. Abdominal and pelvic Magnetic resonance
      will be performed 1, 6 and 12 months after the surgery. Transvaginal ultrasound will be
      performed 2, 4 and 6 months after the surgery. Hormonal evaluation will be performed every 3
      months. Tumor follow-up will be performed according to the institution protocols. It is
      recommend to the patients to wait for 1 year before trying pregnancy.

      Reports concerning safety will be presented every 6 months to the local Ethics Committee. No
      uterine necrosis is expected and in case of 2 uterine necrosis, the study will be stoped. Up
      to two local recurrences in the study period are accepted, but in case of a third recurrence,
      the study will be stoped. All complication will be reviewed by the local board and the study
      will be under permanent evaluation. Every 6 months the local board will provide a report
      allowing the study to continue or not.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Recruitment completed. Final data collection in April/2020.
primary purpose: Other
masking: None (Open Label)
measure: Uterine preservation after transposition to the upper abdomen and replacement in the pelvis
time frame: 6 months
description: The preservation of the uterus with normal endometrium confirmed by ultra-sound, after the surgery to place it in the upper abdomen and after replacing the uterus back to its normal position.
measure: Morbidity
time frame: 6 months
description: Intraoperative and postoperative complications
measure: Cancer recurrence
time frame: Through study completion, an average of 2 years
description: Local and distant recurrences
arm group label: Uterine Transposition
arm group type: Experimental
description: Patients submitted to uterine transposition.
intervention type: Procedure
intervention name: Uterine transposition.
description: Surgical transposition of the uterus to the upper abdomen. After the end of radiotherapy, rectosigmoidectomy is performed and the uterus is repositioned into the pelvis.
arm group label: Uterine Transposition
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: No
last name: Reitan Ribeiro, MD
role: Principal Investigator
affiliation: Erasto Gaertner Hospital
facility: 
country: Brazil
url: https://erastogaertner.com.br/
description: Erasto Gaertner Hospital webpage
responsible party type: Principal Investigator
investigator affiliation: Hospital Erasto Gaertner
investigator full name: Reitan Ribeiro
investigator title: MD
mesh term: Postoperative Complications
mesh term: Intraoperative Complications
sharing ipd: No
ipd description: Hospital Ethics Committee did not approve individual participant data sharing. Recruitment completed. Final data collection in April/2020.