Evaluation of Sentinel Node Policy in Early Stage Endometrial Carcinomas at Intermediate and High Risk of Recurrence. (SENTIRAD)

Randomized Trial Comparing Sentinel Node (SN) Policy to Current French Initial Staging Protocols in Early Stage Endometrial Carcinomas at Intermediate and High Risk of Recurrence

The aim of this trial is to evaluate the sentinel node policy in early stage endometrial carcinomas at intermediate and high risk of recurrence (by comparing the sentinel node policy to current initial staging protocols).

Study Overview

• Status: Active, not recruiting
• Conditions: Endometrioid Carcinoma; Non Endometrioid Carcinoma
• Intervention / Treatment: Drug: Pre-operative SN mapping with radionucleide; Drug: Intra-operative SN mapping with patent V blue dye; Drug: Intra-operative SN mapping with indocyanin green; Procedure: Full bilateral laparoscopic lymphadenectomy and Hysterectomy; Procedure: Current initial staging protocols

Detailed Description

1. Routine exams required for diagnosis:

   • Endometrioid biopsy or product of a dilatation-curettage under hysteroscopy for diagnosis of histologic typing
   • Tumor assessment: Lombopelvic MRI (1.5 or 3T) with gadolinium injection, studied by steady and dynamic sequences. US and CT-Scan in case of intolerance to MRI should be discussed. FDG-PET may be an option.
2. Tumor board: The completed chart will be reviewed to confirm the risk group and indication.
3. Complete physical and gynecological examination by surgical oncologist followed by a consultation of anesthesiology to confirm the operability of patient.
4. Informed and signed consent form.

5. Study baseline assessment.

   Then,

6. Surgery should be performed within a maximum of 4 weeks from the first consultation, according arm allocated:

   Arm A: Sentinel node policy*

   Arm B:

   • Bilateral pelvic lymphadenectomy (intermediate risk endometrioid)
   • Or Ilio-infrarenal paraaortic lymphadenectomy (high risk endometrioid)

   • Or Pelvic + paraaortic lymphadenectomies (high risk non endometrioid)*

     • along with a peritoneal staging for each arm (cytology, random biopsies, infracolic omentectomy)
7. Second tumor board: after definitive pathological results of the hysterectomy-annexectomy and node (sentinel or not) specimens.

• Study Type: Interventional
• Enrollment (Actual): 262
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Avignon, France, 84036
    • Polyclinique Urbain V
  • Besançon, France, 25000
    • Centre Hospitalier Régional Universitaire
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Clermont-Ferrand, France, 63011
    • Centre Jean Perrin
  • Dijon, France
    • Centre Georges Francois Leclerc
  • Lille, France, 59020
    • Centre Oscar Lambret
  • Lille, France, 59037
    • Hôpital Jeanne de Flandres, CHRU Lille
  • Limoges, France, 87042
    • Hôpital Mère-Enfant, CHU Limoges
  • Lyon, France, 69008
    • Centre Leon Berard
  • Marseille, France, 13273
    • Institut Paoli Calmettes
  • Montpellier, France, 34298
    • ICM Val d'Aurelle
  • Paris, France, 75015
    • Hopital Europeen Georges Pompidou
  • Paris, France, 75013
    • Hôpital La Pitié-Salpétrière
  • Saint-Herblain, France, 44805
    • Institut de Cancérologie de l'Ouest, René Gauducheau
  • Strasbourg, France, 67065
    • Centre Paul Strauss
  • Toulouse, France, 31059
    • Institut Claudius Regaud

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients with early endometrial carcinoma with early FIGO clinical stage I-II (clinical examination, abdomino-pelvic MRI/Ultrasound - or CT scan if MRI not possible - and endometrial biopsy or curettage), then stratification of the recurrence risk as defined by last European Society for Medical Oncology (ESMO) guidelines :

   • Intermediate-risk endometrioid (type 1): FIGO stage IA/T1a grade 3, or IB grade 1 or 2
   • Or High risk endometrioid (type 1) : FIGO stage IB/T1b grade 3, or II grade 1 or 2 or 3
   • Or High risk non endometrioid (type 2) : FIGO stages I-II
2. Without any suspicious pelvic, paraaortic, distant node at preoperative MRI
3. Age ≥ 18 years
4. Performance status (OMS) ≤ 2
5. No contraindication to surgery
6. Absence of known hypersensitivity to colloidal rhenium sulphide and technetium (nanocolloid) or one of its excipients, to human albumin preparations, to Nanocoll® and Rotop-nanoHSA® and their excipients, to injectable dyes (blue dye or indocyanine green if available) or one of their excipients, to triphenylmethane derivatives
7. Signed and dated informed consent
8. Effective contraception for patients with reproductive potential
9. Patient affiliated with a health insurance system

Exclusion Criteria:

1. Preoperative workup with :

   • Previous hysterectomy (by nature, this trial cannot be offered as a secondary staging procedure)
   • non carcinoma (for example sarcoma, trophoblastic tumor)
   • Low-risk endometrioid carcinoma as defined by the ESMO: 2009 FIGO stage IA grade 1-2
   • Metastatic disease at preoperative workup
   • Suspicious adenopathy at preoperative workup
2. Pregnant and/or breastfeeding woman
3. No understanding of the trial
4. Patient deprived of liberty or in guardianship
5. Inexperience of the trial site in pelvic sentinel node detection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pre-operative SN mapping with radionucleide; 1 Pre-operative Sentinel Node (SN) mapping with Nanocis or Nanocoll or Rotop-nanoHSA 2- Intra-operative SN mapping with patent V blue dye, or Intra-operative SN mapping with indocyanin green for patients with known hypersensitivity, allergy to patent V blue dye 3- Full bilateral laparoscopic lymphadenectomy and Hysterectomy: If bilateral SN are detected, all positive SN are removed, then the surgeon proceeds to a total hysterectomy. If unilateral SN are detected, surgeon will complete intervention with pelvic LN dissection on the opposite side, in accordance with risk group definition (ex: omentectomy for high-risk non endometrioid carcinomas). If non SN are detected, surgeon will proceed to a total hysterectomy, a bilateral salpingo-oophorectomy, a complete and bilateral pelvic LND with more enlarged dissection regardless the pathology	Drug: Pre-operative SN mapping with radionucleide; Preparation : four 1ml syringe (Nanocis, or Nanocoll, or Rotop-nanoHSA) are prepared per patient, each containing a total activity 10 MBq if the injection is planned the same day of surgery and in the operative theater OR each containing a total activity 30MBq if the injection is performed the day before the surgery.; Intracervical injection is performed by the surgeon, no more than 3-24 hours before surgery : 4 submucous injections with the filtered radiocolloid at 3, 6, 9 and 12 o'clock positions. Each injection if performed at 2 mm of depth for a total activity of 40 MBq or a total activity of 120 MBq is the surgery is planned the day after the injection.; Sentinel Node detection by planar scintigraphy at 1 and 3h (if no detection at 1 hour), or by SPECT-CT imaging if available.; Other Names: Pre-operative Sentinel Node; Drug: Intra-operative SN mapping with patent V blue dye; Patent blue V dye are diluted with saline sterile solution to obtain 4ml of 50%. Four 1ml syringe, each containing a 50% patent blue dye solution, are prepared per patient.; Intracervical injection is performed by the surgeon. after anesthesis induction and incising the skin,under laparoscopic / laparotomy control to detect intraperitoneal injection of the tracer. Sub-mucous injections are performed with 50% diluted dye at 3 and 9 o'clock positions. At each positions : 1ml is injected deep into the stroma of the cervix (1cm), another 1ml is injected superficially (at 2mm depth). The time between the injection of the dye and the search for the SN must be as shortest as possible.; SN are detected by direct visualization of blue colored lymphatics and node; Other Names: Intra-operative SN mapping; Drug: Intra-operative SN mapping with indocyanin green; 1: Infracyanine powder is diluted in aqueous sterile water to obtain 4ml with a concentration of 1.25 mg/mL. Four 1ml syringe, each containing a 1.25 mg/mL Infracyanine dye solution, are prepared per patient. 2- Intracervical injection is performed by the surgeon, after anesthesis induction and incising the skin,under laparoscopic / laparotomy control to detect intraperitoneal injection of the tracer. Sub-mucous injections are performed with 50% diluted dye at 3 and 9 o'clock positions. At each positions : 1ml is injected deep into the stroma of the cervix (1cm), another 1ml is injected superficially (at 2mm depth). The time between the injection of the dye and the search for the SN must be as shortest as possible 3- SN detection by near-infrared fluorescence imaging; Other Names: Intra-operative Sentinel Node (SN) mapping with Infracyanine; Procedure: Full bilateral laparoscopic lymphadenectomy and Hysterectomy; Bilateral pelvic lymphadenectomy (intermediate risk endometrioid); Or Ilio-infrarenal paraaortic lymphadenectomy (high risk endometrioid); Or Pelvic + paraaortic lymphadenectomies (high risk non endometrioid); Other Names: Full bilateral lymphadenectomy
Other: B : Current initial staging protocols; Current initial staging protocols	Procedure: Current initial staging protocols; Current French initial staging protocols

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morbidity	Per-operative morbidity will be assessed during surgery according to the Oslo classification of intraoperative unfavourable incidents. Early post-operative morbidity will be assessed up to 30 days and scored according to Clavien-Dindo scale. Distant complications, beyond day 30 for patients with no indication of a secondary surgical staging (e.g. secondary paraaortic dissection for pelvic pN1) will be evaluated in accordance with the NCI-CTCAE scale v4.03	Up to 3 after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of detected sentinel node	number of patients with ≥ 1 Sentinel Node (SN) / total number of explored patients, and bilaterality	During surgery
Rate of pN1	n pN1 / total N	an average of 1 month after surgery
Disease free survival	Time from the date of randomization to the first documentation of local, regional or distant disease or death, whichever occurs first.	Up to 5 years after surgery
Overall survival	Time from the date of randomization to the date of death (indicate if the death is due to disease progression or not).	Up to 5 years after surgery
Pronostic value of L1CAM on the risk of reccurrence	A standard staining with HES is carried out in a systematic manner as well as immunohistochemistry with polyclonal anti-L1CAM. If 10% or more of the tumor cells showed L1CAM staining, the sample is rated positive. The rate of L1CAM positive sample will be further correlated with the node involvement and disease recurrence.	an average of 1 month after surgery
Proteomic signature of positive SN	Detection of SN involvement with proteomics	an average of 1 year after surgery

Collaborators and Investigators

• Sponsor: Centre Oscar Lambret
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France; National Cancer Institute, France; Canceropôle Nord Ouest
• Investigators: Study Director: Lucie BRESSON, MD, Centre Oscar Lambret

Publications and helpful links

General Publications

• Aboulouard S, Wisztorski M, Duhamel M, Saudemont P, Cardon T, Narducci F, Lemaire AS, Kobeissy F, Leblanc E, Fournier I, Salzet M. In-depth proteomics analysis of sentinel lymph nodes from individuals with endometrial cancer. Cell Rep Med. 2021 Jun 15;2(6):100318. doi: 10.1016/j.xcrm.2021.100318. eCollection 2021 Jun 15.

Helpful Links

• Results of proteomics profiling of sentinel lymph nodes

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2015
• Primary Completion (Actual): October 1, 2024
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: November 3, 2015
• First Submitted That Met QC Criteria: November 4, 2015
• First Posted (Estimated): November 5, 2015

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Sentinel node
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Genital Diseases, Female; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Carcinoma; Uterine Neoplasms; Endometrial Neoplasms; Ovarian Neoplasms; Carcinoma, Endometrioid; Surgical Procedures, Operative; Urogenital Surgical Procedures; Gynecologic Surgical Procedures; Hysterectomy
• Other Study ID Numbers: SENTIRAD-1502; PHRC-K14-184 (Other Grant/Funding Number: DGOS/INCA); 2024-513079-42-00 (Ctis); 2015-001732-38 (EudraCT Number)

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
• product manufactured in and exported from the U.S.: No