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

Endometrial Carcinoma Clinical Trial

— SENTIRAD  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02598219
• Other study ID #: SENTIRAD-1502
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 2015
• Est. completion date: October 2027

Study information

• Verified date: December 2023
• Source: Centre Oscar Lambret
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 262
• Est. completion date: October 2027
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Endometrial Carcinoma
• Endometrial Neoplasms
• Recurrence

Intervention

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.
• 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
• 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

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)
• Current initial staging protocols
Current French initial staging protocols

Locations

Country	Name	City	State
France	Polyclinique Urbain V	Avignon
France	Centre Hospitalier Régional Universitaire	Besançon
France	Institut Bergonié	Bordeaux
France	Centre Jean Perrin	Clermont-Ferrand
France	Centre Georges François Leclerc	Dijon
France	Centre Oscar Lambret	Lille
France	Hôpital Jeanne de Flandres, CHRU Lille	Lille
France	Hôpital Mère-Enfant, CHU Limoges	Limoges
France	Centre Léon Bérard	Lyon
France	Institut Paoli Calmettes	Marseille
France	ICM Val d'Aurelle	Montpellier
France	Hôpital Européen Georges Pompidou	Paris
France	Hôpital La Pitié-Salpêtrière	Paris
France	Institut de Cancérologie de l'Ouest, René Gauducheau	Saint-Herblain
France	Centre Paul Strauss	Strasbourg
France	Institut Claudius Regaud	Toulouse

Sponsors (4)

Lead Sponsor	Collaborator
Centre Oscar Lambret	Canceropôle Nord Ouest, Institut National de la Santé Et de la Recherche Médicale, France, National Cancer Institute, France

Country where clinical trial is conducted

France, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Rate of detected sentinel node	number of patients with = 1 Sentinel Node (SN) / total number of explored patients, and bilaterality	During surgery
Secondary	Rate of pN1	n pN1 / total N	an average of 1 month after surgery
Secondary	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
Secondary	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
Secondary	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
Secondary	Proteomic signature of positive SN	Detection of SN involvement with proteomics	an average of 1 year after surgery

External Links

•   Results of proteomics profiling of sentinel lymph nodes