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 (PMMR)

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).

Study Overview

• Status: Recruiting
• Conditions: Endometrial Cancer
• Intervention / Treatment: Procedure: Peritoneal Mesometrial Resetion + Targeted Compartmental Lymphadenectomy (PMMR+TCL)

• Study Type: Observational
• Enrollment (Anticipated): 500

Contacts and Locations

• Study Contact: Name: Paul Buderath, Dr.; Phone Number: +492017232442; Email: paul.buderath@uk-essen.de
• Study Contact Backup: Name: Rainer Kimmig, Prof.; Phone Number: +492017232441; Email: rainer.kimmig@uk-essen.de

Study Locations

• Germany
  • NRW
    • Essen, NRW, Germany, 45122
      • Recruiting
      • University Hospital Essen, Department of Gynaecology
      • Contact: Paul Buderath, Dr.; Phone Number: +492017232442; Email: paul.buderath@uk-essen.de
      • Contact: Rainer Kimmig, Prof.; Phone Number: +492017232441; Email: rainer.kimmig@uk-essen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Women with the primary diagnosis of histologically proven endometrial carcinoma: endometroid and non-endometroid FIGO stages I-III; Karnofsky-Index ≥ 70; unrestricted operability; Age >=18 years.

Description

Inclusion Criteria:

• - Histologically proven endometrial carcinoma: endometroid and non-endometroid FIGO stages I-III; Karnofsky-Index ≥ 70; unrestricted operability; Age >=18 years.
• Completed treatment with according Cohort A, PMMR/targeted compartmental pelvic/paraaortic +/- complete pelvic and paraaortic LNE without adjuvant radiotherapy by the responsible clinic (clinician).

or

• Completed treatment according Cohort B, current clinical practice including adjuvant treatment based on ESMO/ESGO/ESTRO guidelines [26] by the responsible clinic (clinician).
• Informed consent of the patient

Exclusion Criteria:

• - Uterine pure sarcoma
• Distant metastases; sclerodermia, lupus erythematodes, mixed connective tissue disease; secondary malignancy; previous radiotherapy of the pelvis.
• Pregnancy
• Patients with diseases of the connective tissue will be excluded because of unforeseeable (e.g. neurological) symptoms and disorders after surgery.
• Postoperative radiotherapy could be administered with respect to the surgical field in R1 situation or if >= 5 lymph nodes were involved; in all other situations adjuvant radiotherapy will be an exclusion criterion for participation in the study cohort A. The patient may be offered documentation in analogy but apart from the study protocol.
• Patient who concomitantly participate in other studies may also be included in this study as long as inclusion criteria of this study are met, follow up data will be available and they do not experience an exclusion criterion.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort A; PMMR + TCL, followed by systematic lymphadenectomy in node positive patients.	Procedure: Peritoneal Mesometrial Resetion + Targeted Compartmental Lymphadenectomy (PMMR+TCL); Peritoneal Mesometrial Resetion + Targeted Compartmental Lymphadenectomy (PMMR+TCL)
Cohort B; Therapy according to actual guidelines

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Time to recurrence or progression	36 months
Intra- and postoperative complications, incidence of lymph oedema		36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Time to death of any cause	36 months
Rate of locoregional relapse and rate of distant metastases at 3 years.		36 months
Pelvic organ functioning	Therapy-induced morbidity on bladder/urethra, rectum/bowel, vagina/vulva, assessed by the LENT-SOMA scoring system	36 months
QoL	Quality of life by EORTC-QLQ-C30 questionnaire at 12 and 24 months after surgery.	36 months

Collaborators and Investigators

• Sponsor: Dr. Paul Buderath
• Investigators: Principal Investigator: Rainer Kimmig, Prof., University Hospital, Essen

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2017
• Primary Completion (Anticipated): January 1, 2025
• Study Completion (Anticipated): January 1, 2030

Study Registration Dates

• First Submitted: August 4, 2020
• First Submitted That Met QC Criteria: August 4, 2020
• First Posted (Actual): August 7, 2020

Study Record Updates

• Last Update Posted (Actual): August 7, 2020
• Last Update Submitted That Met QC Criteria: August 4, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Endometrial Neoplasms
• Other Study ID Numbers: PMMR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No