Evaluation of Sentinel Node Policy in Early Stage Endometrial Carcinomas At Intermediate and High Risk of Recurrence.
- Conditions
- Endometrial Carcinoma
- Interventions
- Drug: Pre-operative SN mapping with radionucleideProcedure: Current initial staging protocolsDrug: Intra-operative SN mapping with patent V blue dyeDrug: Intra-operative SN mapping with indocyanin greenProcedure: Full bilateral laparoscopic lymphadenectomy and Hysterectomy
- Registration Number
- NCT02598219
- Lead Sponsor
- Centre Oscar Lambret
- Brief 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).
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 262
-
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
-
Without any suspicious pelvic, paraaortic, distant node at preoperative MRI
-
Age ≥ 18 years
-
Performance status (OMS) ≤ 2
-
No contraindication to surgery
-
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
-
Signed and dated informed consent
-
Effective contraception for patients with reproductive potential
-
Patient affiliated with a health insurance system
-
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
-
Pregnant and/or breastfeeding woman
-
No understanding of the trial
-
Patient deprived of liberty or in guardianship
-
Inexperience of the trial site in pelvic sentinel node detection
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pre-operative SN mapping with radionucleide Intra-operative SN mapping with patent V blue dye 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 Pre-operative SN mapping with radionucleide 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 Pre-operative SN mapping with radionucleide Full bilateral laparoscopic lymphadenectomy and Hysterectomy 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 Pre-operative SN mapping with radionucleide Intra-operative SN mapping with indocyanin green 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 B : Current initial staging protocols Current initial staging protocols Current initial staging protocols
- Primary Outcome Measures
Name Time Method Morbidity Up to 3 after surgery 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
- Secondary Outcome Measures
Name Time Method Rate of detected sentinel node During surgery number of patients with ≥ 1 Sentinel Node (SN) / total number of explored patients, and bilaterality
Rate of pN1 an average of 1 month after surgery n pN1 / total N
Disease free survival Up to 5 years after surgery Time from the date of randomization to the first documentation of local, regional or distant disease or death, whichever occurs first.
Overall survival Up to 5 years after surgery Time from the date of randomization to the date of death (indicate if the death is due to disease progression or not).
Pronostic value of L1CAM on the risk of reccurrence an average of 1 month after surgery 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.
Proteomic signature of positive SN an average of 1 year after surgery Detection of SN involvement with proteomics
Trial Locations
- Locations (16)
Institut Bergonié
🇫🇷Bordeaux, France
Centre Hospitalier Régional Universitaire
🇫🇷Besançon, France
Centre Jean Perrin
🇫🇷Clermont-Ferrand, France
Polyclinique Urbain V
🇫🇷Avignon, France
Hôpital Mère-Enfant, CHU Limoges
🇫🇷Limoges, France
Centre Oscar Lambret
🇫🇷Lille, France
Centre Léon Bérard
🇫🇷Lyon, France
Centre Paul Strauss
🇫🇷Strasbourg, France
Institut Paoli Calmettes
🇫🇷Marseille, France
ICM Val d'Aurelle
🇫🇷Montpellier, France
Institut de Cancérologie de l'Ouest, René Gauducheau
🇫🇷Saint-Herblain, France
Hôpital La Pitié-Salpêtrière
🇫🇷Paris, France
Hôpital Européen Georges Pompidou
🇫🇷Paris, France
Institut Claudius Regaud
🇫🇷Toulouse, France
Centre Georges François Leclerc
🇫🇷Dijon, France
Hôpital Jeanne de Flandres, CHRU Lille
🇫🇷Lille, France