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

Primary Purpose

Endometrial Carcinoma

Status
Active
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Pre-operative SN mapping with radionucleide
Intra-operative SN mapping with patent V blue dye
Intra-operative SN mapping with indocyanin green
Full bilateral laparoscopic lymphadenectomy and Hysterectomy
Current initial staging protocols
Sponsored by
Centre Oscar Lambret
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Endometrial Carcinoma focused on measuring Sentinel node

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Polyclinique Urbain V
  • Centre Hospitalier Régional Universitaire
  • Institut Bergonié
  • Centre Jean Perrin
  • Centre Georges François Leclerc
  • Centre Oscar Lambret
  • Hôpital Jeanne de Flandres, CHRU Lille
  • Hôpital Mère-Enfant, CHU Limoges
  • Centre Léon Bérard
  • Institut Paoli Calmettes
  • ICM Val d'Aurelle
  • Hôpital La Pitié-Salpêtrière
  • Hôpital Européen Georges Pompidou
  • Institut de Cancérologie de l'Ouest, René Gauducheau
  • Centre Paul Strauss
  • Institut Claudius Regaud

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

Pre-operative SN mapping with radionucleide

B : Current initial staging protocols

Arm Description

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

Current initial staging protocols

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Rate of detected sentinel node
number of patients with ≥ 1 Sentinel Node (SN) / total number of explored patients, and bilaterality
Rate of pN1
n pN1 / total N
Disease free survival
Time from the date of randomization to the first documentation of local, regional or distant disease or death, whichever occurs first.
Overall survival
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
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
Detection of SN involvement with proteomics

Full Information

First Posted
November 3, 2015
Last Updated
December 6, 2022
Sponsor
Centre Oscar Lambret
Collaborators
National Cancer Institute, France, Institut National de la Santé Et de la Recherche Médicale, France, Canceropôle Nord Ouest
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1. Study Identification

Unique Protocol Identification Number
NCT02598219
Brief Title
Evaluation of Sentinel Node Policy in Early Stage Endometrial Carcinomas at Intermediate and High Risk of Recurrence.
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 2015 (Actual)
Primary Completion Date
October 2024 (Anticipated)
Study Completion Date
October 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Oscar Lambret
Collaborators
National Cancer Institute, France, Institut National de la Santé Et de la Recherche Médicale, France, Canceropôle Nord Ouest

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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
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. Tumor board: The completed chart will be reviewed to confirm the risk group and indication. Complete physical and gynecological examination by surgical oncologist followed by a consultation of anesthesiology to confirm the operability of patient. Informed and signed consent form. Study baseline assessment. Then, 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) Second tumor board: after definitive pathological results of the hysterectomy-annexectomy and node (sentinel or not) specimens.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Endometrial Carcinoma
Keywords
Sentinel node

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
262 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pre-operative SN mapping with radionucleide
Arm Type
Experimental
Arm Description
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
Arm Title
B : Current initial staging protocols
Arm Type
Other
Arm Description
Current initial staging protocols
Intervention Type
Drug
Intervention Name(s)
Pre-operative SN mapping with radionucleide
Other Intervention Name(s)
Pre-operative Sentinel Node
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Intra-operative SN mapping with patent V blue dye
Other Intervention Name(s)
Intra-operative SN mapping
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Intra-operative SN mapping with indocyanin green
Other Intervention Name(s)
Intra-operative Sentinel Node (SN) mapping with Infracyanine
Intervention Description
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
Intervention Type
Procedure
Intervention Name(s)
Full bilateral laparoscopic lymphadenectomy and Hysterectomy
Other Intervention Name(s)
Full bilateral lymphadenectomy
Intervention Description
Bilateral pelvic lymphadenectomy (intermediate risk endometrioid) Or Ilio-infrarenal paraaortic lymphadenectomy (high risk endometrioid) Or Pelvic + paraaortic lymphadenectomies (high risk non endometrioid)
Intervention Type
Procedure
Intervention Name(s)
Current initial staging protocols
Intervention Description
Current French initial staging protocols
Primary Outcome Measure Information:
Title
Morbidity
Description
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
Time Frame
Up to 3 after surgery
Secondary Outcome Measure Information:
Title
Rate of detected sentinel node
Description
number of patients with ≥ 1 Sentinel Node (SN) / total number of explored patients, and bilaterality
Time Frame
During surgery
Title
Rate of pN1
Description
n pN1 / total N
Time Frame
an average of 1 month after surgery
Title
Disease free survival
Description
Time from the date of randomization to the first documentation of local, regional or distant disease or death, whichever occurs first.
Time Frame
Up to 5 years after surgery
Title
Overall survival
Description
Time from the date of randomization to the date of death (indicate if the death is due to disease progression or not).
Time Frame
Up to 5 years after surgery
Title
Pronostic value of L1CAM on the risk of reccurrence
Description
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.
Time Frame
an average of 1 month after surgery
Title
Proteomic signature of positive SN
Description
Detection of SN involvement with proteomics
Time Frame
an average of 1 year after surgery

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carlos MARTINEZ GOMEZ, MD
Organizational Affiliation
Centre Oscar Lambret
Official's Role
Study Director
Facility Information:
Facility Name
Polyclinique Urbain V
City
Avignon
ZIP/Postal Code
84036
Country
France
Facility Name
Centre Hospitalier Régional Universitaire
City
Besançon
ZIP/Postal Code
25000
Country
France
Facility Name
Institut Bergonié
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
Centre Jean Perrin
City
Clermont-Ferrand
ZIP/Postal Code
63011
Country
France
Facility Name
Centre Georges François Leclerc
City
Dijon
Country
France
Facility Name
Centre Oscar Lambret
City
Lille
ZIP/Postal Code
59020
Country
France
Facility Name
Hôpital Jeanne de Flandres, CHRU Lille
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Hôpital Mère-Enfant, CHU Limoges
City
Limoges
ZIP/Postal Code
87042
Country
France
Facility Name
Centre Léon Bérard
City
Lyon
ZIP/Postal Code
69008
Country
France
Facility Name
Institut Paoli Calmettes
City
Marseille
ZIP/Postal Code
13273
Country
France
Facility Name
ICM Val d'Aurelle
City
Montpellier
ZIP/Postal Code
34298
Country
France
Facility Name
Hôpital La Pitié-Salpêtrière
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
Hôpital Européen Georges Pompidou
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
Institut de Cancérologie de l'Ouest, René Gauducheau
City
Saint-Herblain
ZIP/Postal Code
44805
Country
France
Facility Name
Centre Paul Strauss
City
Strasbourg
ZIP/Postal Code
67065
Country
France
Facility Name
Institut Claudius Regaud
City
Toulouse
ZIP/Postal Code
31059
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34195683
Citation
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.
Results Reference
result
Links:
URL
https://pubmed.ncbi.nlm.nih.gov/34195683/
Description
Results of proteomics profiling of sentinel lymph nodes

Learn more about this trial

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

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