Clinical trial NCT05687084: Uterine Manipulator Versus No Uterine Manipulator in Endometrial Cancer Trial
Official title: Randomized Controlled Trial on the Oncologic Outcomes of Use Versus Not Use of the Uterine Manipulator in the Surgical Treatment of Apparent Uterine-confined Endometrial Carcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Endometrial Neoplasms
Keywords: Endometrial Neoplasms
Uterine manipulator
Laparoscopic hysterectomy
Recurrence-free survival
Cause-specific survival
Overall survival
Oncologic outcomes
Lead sponsor: Universita di Verona
Sponsor class: OTHER
First posted: 2023-01-17
Enrollment: 1030
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter, parallel arms, open-label, randomized controlled trial.
Primary purpose: TREATMENT

Brief summary: Minimally invasive surgery is the recommended approach in endometrial cancer (EC) patients based on the results of two randomized controlled trials, given its advantages without compromised oncologic outcomes. The uterine manipulator is commonly used in benign and malignant pathologies to perform a laparoscopic or robotic hysterectomy. However, although regularly used, the uterine manipulator adoption in EC is a controversial technical aspect due to the raised concerns regarding the possible risk of disruption of the tumor mass, the spread of malignant cells, and seeding of the disease, particularly at the level of the vaginal cuff or spread of tumor cells, with increased risk of recurrence and death due to EC. On that basis, given that hysterectomy without a uterine manipulator is feasible, only a randomized controlled trial comparing oncologic outcomes in EC patients after use versus not use of the uterine manipulator will be able to provide high-quality evidence to answer this critical question and allow or exclude the use of a uterine manipulator during minimally invasive hysterectomy for EC.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of Endometrial Cancer of any histology (including carcinosarcoma) and grade
* Planned surgical treatment including hysterectomy and bilateral salpingo-oophorectomy (ovarian preservation in selected patients is not an exclusion criterion)
* Age ≥ 18 years
* No preoperative evidence of extrauterine disease (Clinical stage IIIA, IIIB)
* No preoperative evidence of suspicious lymph nodes (Clinical stage IIIC)
* No preoperative evidence of distant metastasis (Clinical stage IV)
* Approved and signed informed consent

Exclusion Criteria:

* Neoadjuvant therapy
* Synchronous or previous (\< 5 years) invasive cancer, not including non-melanoma skin cancer
* Fertility preservation
* World Health Organization performance score \> 2
* Uterine sarcoma
* Previous pelvic/abdominal radiotherapy, hormone therapy for cancer (\< 5 years), chemotherapy (\< 5 years), pelvic or paraaortic lymphadenectomy, or retroperitoneal surgery
* Inadequate bone marrow function (white blood cells \<3·0×109/L, platelets \<100×109/L)
* Inadequate liver function (bilirubin \>1.5×upper normal limit \[UNL\], aspartate aminotransferase, and alanine aminotransferase \>2.5 × UNL)
* Inadequate kidney function (creatinine clearance \< 60 mL per min calculated according to Cockcroft-Gault 10 or \< 50 mL per min Ethylenediaminetetraacetic acid clearance)
* Intraoperative evidence of stage IV disease

Primary outcomes:
measure: Recurrence-free survival
timeFrame: Each follow-up visit, up to 4 years from the day of surgery
Secondary outcomes:
measure: Cause-specific survival
timeFrame: Each follow-up visit, up to 4 years from the day of surgery
measure: Overall survival
timeFrame: Each follow-up visit, up to 4 years from the day of surgery
measure: Site-specific recurrence-free survival
timeFrame: Each follow-up visit, up to 4 years from the day of surgery
measure: Operative time
timeFrame: Day of surgery
measure: Intraoperative blood loss
timeFrame: Day of surgery
measure: 30-day post-surgical morbidity
timeFrame: 30 days after surgery
measure: Lymphovascular space invasion
timeFrame: Day of surgery
measure: Peritoneal cytology
timeFrame: Day of surgery
measure: Quality of life indexes
timeFrame: Each follow-up visit, up to 4 years from the day of surgery
Other outcomes:
Locations:
city: Cuneo
country: Italy
facility: UOC Ostetricia e Ginecologia, Azienda Ospedaliera Santa Croce e Carle
city: Reggio Emilia
country: Italy
facility: UOC Ostetricia e Ginecologia, Arcispedale Santa Maria Nuova
city: Verona
country: Italy
facility: AOUI Verona - University of Verona - Department of Obstetrics and Gynecology
Study officials:
affiliation: AOUI Verona - University of Verona
name: Stefano Uccella, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: AOUI Verona - University of Verona
name: Simone Garzon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: AOUI Verona - University of Verona
name: Pier Carlo Zorzato, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Concin N, Matias-Guiu X, Vergote I, Cibula D, Mirza MR, Marnitz S, Ledermann J, Bosse T, Chargari C, Fagotti A, Fotopoulou C, Gonzalez Martin A, Lax S, Lorusso D, Marth C, Morice P, Nout RA, O'Donnell D, Querleu D, Raspollini MR, Sehouli J, Sturdza A, Taylor A, Westermann A, Wimberger P, Colombo N, Planchamp F, Creutzberg CL. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Int J Gynecol Cancer. 2021 Jan;31(1):12-39. doi: 10.1136/ijgc-2020-002230. Epub 2020 Dec 18.
citation: van den Haak L, Alleblas C, Nieboer TE, Rhemrev JP, Jansen FW. Efficacy and safety of uterine manipulators in laparoscopic surgery: a review. Arch Gynecol Obstet. 2015 Nov;292(5):1003-11. doi: 10.1007/s00404-015-3727-9. Epub 2015 May 13.
citation: Uccella S, Cianci S, Gueli Alletti S. Uterine manipulator in endometrial cancer: we are still far from the answer. Am J Obstet Gynecol. 2021 Mar;224(3):332. doi: 10.1016/j.ajog.2020.09.049. Epub 2020 Nov 15. No abstract available.
citation: Uccella S, Bonzini M, Malzoni M, Fanfani F, Palomba S, Aletti G, Corrado G, Ceccaroni M, Seracchioli R, Shakir F, Ferrero A, Berretta R, Tinelli R, Vizza E, Roviglione G, Casarella L, Volpi E, Cicinelli E, Scambia G, Ghezzi F. The effect of a uterine manipulator on the recurrence and mortality of endometrial cancer: a multi-centric study by the Italian Society of Gynecological Endoscopy. Am J Obstet Gynecol. 2017 Jun;216(6):592.e1-592.e11. doi: 10.1016/j.ajog.2017.01.027. Epub 2017 Jan 29.
citation: Padilla-Iserte P, Lago V, Tauste C, Diaz-Feijoo B, Gil-Moreno A, Oliver R, Coronado P, Martin-Salamanca MB, Pantoja-Garrido M, Marcos-Sanmartin J, Gilabert-Estelles J, Lorenzo C, Cazorla E, Roldan-Rivas F, Rodriguez-Hernandez JR, Sanchez L, Muruzabal JC, Hervas D, Domingo S; Spanish Society of Gynecology and Obstetrics Spanish Investigational Network Gynecologic Oncology Group. Impact of uterine manipulator on oncological outcome in endometrial cancer surgery. Am J Obstet Gynecol. 2021 Jan;224(1):65.e1-65.e11. doi: 10.1016/j.ajog.2020.07.025. Epub 2020 Jul 18.