<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/NCT04504006</url>
  </required_header>
  <id_info>
    <org_study_id>PMMR</org_study_id>
    <nct_id>NCT04504006</nct_id>
  </id_info>
  <brief_title>European Collaborative Multicenter Observational Study: Modular Treatment With PMMR and Targeted Compartmental Pelvic Lymphadenectomy Followed by Therapeutic Pelvic and Paraaortic Lymphadenectomy in Node Positive Disease for Locoregional Control in Endometrial Cancer FIGO Stages I-III</brief_title>
  <acronym>PMMR</acronym>
  <official_title>European Collaborative Multicenter Observational Study: Modular Treatment With PMMR and Targeted Compartmental Pelvic Lymphadenectomy Followed by Therapeutic Pelvic and Paraaortic Lymphadenectomy in Node Positive Disease for Locoregional Control in Endometrial Cancer FIGO Stages I-III</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dr. Paul Buderath</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Essen</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>
      Intermediate/high risk endometrial cancer shows locoregional recurrence rates up to 20%. Also&#xD;
      in so called low-risk disease 5-10% incidence of nodal metastasis is reported. Although&#xD;
      adjuvant radiotherapy may reduce these recurrences there has been no survival benefit. To&#xD;
      avoid toxicity of irradiation and preserve the full potential of radiotherapy for salvage&#xD;
      treatment of recurrences surgery should avoid locoregional recurrence. According to the&#xD;
      concept of ontogenetically based compartmental surgery it may be suggested that this may be&#xD;
      achieved by PMMR and therapeutic LNE as it has been already shown for TMMR in cervical cancer&#xD;
      and TME in rectal cancer. First, monocentric data have shown feasibility and safety of this&#xD;
      approach and are promising with respect to reduce locoregional recurrence rate significantly.&#xD;
      On parallel it has also been convincingly shown that sentinel node detection shows a high&#xD;
      level of accuracy in precluding nodal involvement in endometrial cancer. Thus, unnecessary&#xD;
      complete lymphadenectomy may be avoided in patients with proven node negative disease.&#xD;
      However, this procedure is aimed on diagnostic and not therapeutic goals. Nevertheless,&#xD;
      therapeutically it fits well in the surgical concept of compartmental surgery indicating the&#xD;
      peripheral border of therapeutic surgical approach. This leads to the concept to resect the&#xD;
      embryologically determined tissue of risk en bloc together with the &quot;sentinel nodes&quot; of the&#xD;
      draining lymph compartment (module I). In case of positive node extended therapeutic pelvic&#xD;
      and paraaortic lymphadenectomy (module II) may be indicated. This should now be evaluated in&#xD;
      a European collaborative observational trial. The surgical arm (cohort A) will include&#xD;
      Patients who have received surgical treatment (module I) and in case of positive nodes or&#xD;
      enhanced risk for isolated positive paraaortic nodes (module II) and don't want to receive&#xD;
      adjuvant radiation therapy; in intermediate/high risk situations, however, adjuvant&#xD;
      chemotherapy should be offered to these patients. For patients with high-risk carcinomas who&#xD;
      do not want to be treated with the modular concept, the option of receiving systematic&#xD;
      lymphadenectomy during primary surgery will be given. Patients who prefer to be treated&#xD;
      according current clinical practice will be asked to participate in cohort B to be observed&#xD;
      as concomitant control and will be treated according to current clinical practice based on&#xD;
      the European ESMO/ESGO/ESTRO-Guidelines. Primary endpoint will be loco-regional recurrence&#xD;
      and recurrence free survival. Follow up is planned for 5 years following date of first&#xD;
      surgery (module I).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 10, 2017</start_date>
  <completion_date type="Anticipated">January 1, 2030</completion_date>
  <primary_completion_date type="Anticipated">January 1, 2025</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>36 Months</target_duration>
  <primary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>36 months</time_frame>
    <description>Time to recurrence or progression</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Intra- and postoperative complications, incidence of lymph oedema</measure>
    <time_frame>36 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>36 months</time_frame>
    <description>Time to death of any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of locoregional relapse and rate of distant metastases at 3 years.</measure>
    <time_frame>36 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pelvic organ functioning</measure>
    <time_frame>36 months</time_frame>
    <description>Therapy-induced morbidity on bladder/urethra, rectum/bowel, vagina/vulva, assessed by the LENT-SOMA scoring system</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>QoL</measure>
    <time_frame>36 months</time_frame>
    <description>Quality of life by EORTC-QLQ-C30 questionnaire at 12 and 24 months after surgery.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">500</enrollment>
  <condition>Endometrial Cancer</condition>
  <arm_group>
    <arm_group_label>Cohort A</arm_group_label>
    <description>PMMR + TCL, followed by systematic lymphadenectomy in node positive patients.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B</arm_group_label>
    <description>Therapy according to actual guidelines</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Peritoneal Mesometrial Resetion + Targeted Compartmental Lymphadenectomy (PMMR+TCL)</intervention_name>
    <description>Peritoneal Mesometrial Resetion + Targeted Compartmental Lymphadenectomy (PMMR+TCL)</description>
    <arm_group_label>Cohort A</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Women with the primary diagnosis of histologically proven endometrial carcinoma:&#xD;
        endometroid and non-endometroid FIGO stages I-III; Karnofsky-Index ≥ 70; unrestricted&#xD;
        operability; Age &gt;=18 years.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  - Histologically proven endometrial carcinoma: endometroid and non-endometroid FIGO&#xD;
             stages I-III; Karnofsky-Index ≥ 70; unrestricted operability; Age &gt;=18 years.&#xD;
&#xD;
          -  Completed treatment with according Cohort A, PMMR/targeted compartmental&#xD;
             pelvic/paraaortic +/- complete pelvic and paraaortic LNE without adjuvant radiotherapy&#xD;
             by the responsible clinic (clinician).&#xD;
&#xD;
        or&#xD;
&#xD;
          -  Completed treatment according Cohort B, current clinical practice including adjuvant&#xD;
             treatment based on ESMO/ESGO/ESTRO guidelines [26] by the responsible clinic&#xD;
             (clinician).&#xD;
&#xD;
          -  Informed consent of the patient&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  - Uterine pure sarcoma&#xD;
&#xD;
          -  Distant metastases; sclerodermia, lupus erythematodes, mixed connective tissue&#xD;
             disease; secondary malignancy; previous radiotherapy of the pelvis.&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Patients with diseases of the connective tissue will be excluded because of&#xD;
             unforeseeable (e.g. neurological) symptoms and disorders after surgery.&#xD;
&#xD;
          -  Postoperative radiotherapy could be administered with respect to the surgical field in&#xD;
             R1 situation or if &gt;= 5 lymph nodes were involved; in all other situations adjuvant&#xD;
             radiotherapy will be an exclusion criterion for participation in the study cohort A.&#xD;
             The patient may be offered documentation in analogy but apart from the study protocol.&#xD;
&#xD;
          -  Patient who concomitantly participate in other studies may also be included in this&#xD;
             study as long as inclusion criteria of this study are met, follow up data will be&#xD;
             available and they do not experience an exclusion criterion.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rainer Kimmig, Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Essen</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Paul Buderath, Dr.</last_name>
    <phone>+492017232442</phone>
    <email>paul.buderath@uk-essen.de</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Rainer Kimmig, Prof.</last_name>
    <phone>+492017232441</phone>
    <email>rainer.kimmig@uk-essen.de</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University Hospital Essen, Department of Gynaecology</name>
      <address>
        <city>Essen</city>
        <state>NRW</state>
        <zip>45122</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Paul Buderath, Dr.</last_name>
      <phone>+492017232442</phone>
      <email>paul.buderath@uk-essen.de</email>
    </contact>
    <contact_backup>
      <last_name>Rainer Kimmig, Prof.</last_name>
      <phone>+492017232441</phone>
      <email>rainer.kimmig@uk-essen.de</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>August 4, 2020</study_first_submitted>
  <study_first_submitted_qc>August 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2020</study_first_posted>
  <last_update_submitted>August 4, 2020</last_update_submitted>
  <last_update_submitted_qc>August 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 7, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University Hospital, Essen</investigator_affiliation>
    <investigator_full_name>Dr. Paul Buderath</investigator_full_name>
    <investigator_title>PD Dr. med. P. Buderath</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Endometrial 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/NCT04504006
org study id: PMMR
nct id: NCT04504006
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Intermediate/high risk endometrial cancer shows locoregional recurrence rates up to 20%. Also
      in so called low-risk disease 5-10% incidence of nodal metastasis is reported. Although
      adjuvant radiotherapy may reduce these recurrences there has been no survival benefit. To
      avoid toxicity of irradiation and preserve the full potential of radiotherapy for salvage
      treatment of recurrences surgery should avoid locoregional recurrence. According to the
      concept of ontogenetically based compartmental surgery it may be suggested that this may be
      achieved by PMMR and therapeutic LNE as it has been already shown for TMMR in cervical cancer
      and TME in rectal cancer. First, monocentric data have shown feasibility and safety of this
      approach and are promising with respect to reduce locoregional recurrence rate significantly.
      On parallel it has also been convincingly shown that sentinel node detection shows a high
      level of accuracy in precluding nodal involvement in endometrial cancer. Thus, unnecessary
      complete lymphadenectomy may be avoided in patients with proven node negative disease.
      However, this procedure is aimed on diagnostic and not therapeutic goals. Nevertheless,
      therapeutically it fits well in the surgical concept of compartmental surgery indicating the
      peripheral border of therapeutic surgical approach. This leads to the concept to resect the
      embryologically determined tissue of risk en bloc together with the "sentinel nodes" of the
      draining lymph compartment (module I). In case of positive node extended therapeutic pelvic
      and paraaortic lymphadenectomy (module II) may be indicated. This should now be evaluated in
      a European collaborative observational trial. The surgical arm (cohort A) will include
      Patients who have received surgical treatment (module I) and in case of positive nodes or
      enhanced risk for isolated positive paraaortic nodes (module II) and don't want to receive
      adjuvant radiation therapy; in intermediate/high risk situations, however, adjuvant
      chemotherapy should be offered to these patients. For patients with high-risk carcinomas who
      do not want to be treated with the modular concept, the option of receiving systematic
      lymphadenectomy during primary surgery will be given. Patients who prefer to be treated
      according current clinical practice will be asked to participate in cohort B to be observed
      as concomitant control and will be treated according to current clinical practice based on
      the European ESMO/ESGO/ESTRO-Guidelines. Primary endpoint will be loco-regional recurrence
      and recurrence free survival. Follow up is planned for 5 years following date of first
      surgery (module I).
observational model: Cohort
time perspective: Prospective
measure: Progression Free Survival
time frame: 36 months
description: Time to recurrence or progression
measure: Intra- and postoperative complications, incidence of lymph oedema
time frame: 36 months
measure: Overall survival
time frame: 36 months
description: Time to death of any cause
measure: Rate of locoregional relapse and rate of distant metastases at 3 years.
time frame: 36 months
measure: Pelvic organ functioning
time frame: 36 months
description: Therapy-induced morbidity on bladder/urethra, rectum/bowel, vagina/vulva, assessed by the LENT-SOMA scoring system
measure: QoL
time frame: 36 months
description: Quality of life by EORTC-QLQ-C30 questionnaire at 12 and 24 months after surgery.
arm group label: Cohort A
description: PMMR + TCL, followed by systematic lymphadenectomy in node positive patients.
arm group label: Cohort B
description: Therapy according to actual guidelines
intervention type: Procedure
intervention name: Peritoneal Mesometrial Resetion + Targeted Compartmental Lymphadenectomy (PMMR+TCL)
description: Peritoneal Mesometrial Resetion + Targeted Compartmental Lymphadenectomy (PMMR+TCL)
arm group label: Cohort A
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
gender based: Yes
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Rainer Kimmig, Prof.
role: Principal Investigator
affiliation: University Hospital, Essen
last name: Paul Buderath, Dr.
phone: +492017232442
email: paul.buderath@uk-essen.de
last name: Rainer Kimmig, Prof.
phone: +492017232441
email: rainer.kimmig@uk-essen.de
facility: 
status: Recruiting
contact: 
contact backup: 
country: Germany
responsible party type: Sponsor-Investigator
investigator affiliation: University Hospital, Essen
investigator full name: Dr. Paul Buderath
investigator title: PD Dr. med. P. Buderath
mesh term: Endometrial Neoplasms
sharing ipd: No