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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Oscar Lambret

Participant type

Patients

Age range

65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 Nov 2015 → ongoing

Decision date (initial)

2024-08-09

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-513079-42-00

EudraCT number

2015-001732-38

ClinicalTrials.gov

NCT02598219

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis, Others, Safety

To compare the morbidity classified as possibly related to lymph node dissection between the a sentinel node policy (exclusive SN resection  complete pelvic lymphadenectomy on SN-negative side) and the national or European protocols of surgical staging, until 3 years of surgery, in intermediate-risk endometrioid and high-risk endometrioid and non-endometrioid carcinomas (full lymphadenectomy: pelvic, paraaortic or both according to stratification)

Secondary objectives 6

1. To determine the Rate of sentinel node detection, location, laterality
2. To determine the Rate of positive node detection (pN1)
3. To estimate and test the impact of sentinel node policy in terms of Progression Free Survival (PFS)
4. To estimate and test the impact of sentinel node policy in terms of Specific and Overall Survival (OS), indicate if the death is due to disease progression or not
5. Exploratory : To evaluate the expression L1CAM on uterine specimens
6. Exploratory : Proteomic diagnosis of node metastases

Conditions and MedDRA coding

Intermediate-risk, high risk endometrial cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

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 ESMO guidelines: • Strata A - Intermediate-risk endometrioid (type 1): 2009 FIGO stage IA/T1a grade 3, or IB grade 1 or 2 Or • Strata B - High risk endometrioid (type 1): 2009 FIGO stages IB/T1b, grade 3. FIGO stage II, grade 1 or 2 or 3. Or • Strata C - High risk non endometrioid (type 2): 2009 FIGO stages I-II
2. Without any suspicious pelvic, paraaortic, distant node at preoperative MRI (lombo-pelvic MRI or pelvic MRI associated with whole body scintigraphy)
3. Age ≥ 18 years
4. Performance status (OMS) ≤ 2
5. No contraindication to surgery
6. Absence of known hypersensitivity: • to colloidal rhenium sulphide and technecium (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 5

1. Preoperative workup with: - Previous hysterectomy (by nature, this trial cannot be offered as a secondary staging procedure) - Non carcinoma (for exemple sarcoma, trophoblastic tumor) - Low-risk endometrioïd carcinoma as defined by ESMO: 2009 FIGO stage IA grade 1-2 - Metastastic 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Per-operative morbidity will be assessed during surgery according to the Oslo classification of intraoperative unfavourable incidents. Adverse effects possibly related to node dissection will be assessed at per-operative timepoint, in particular: - vascular (including blood loss) - urinary - digestive - and nervous system related disorders
2. Early post-operative morbidity possibly related to node dissection will be assessed up to 30 days and scored according to Clavien-Dindo scale: - post-operative complications (vascular, urinary, digestive, nervous complications), - symptomatic lymphocysts (necessitating pain killers or punctions) and leg lymphedemas whatever the intensity and duration (preoperative and postoperative legs and thigh measurements. Post-operative events of grade II or more defined by Clavien-Dindo scale
3. Distant complications, beyond day 30 for patients (e.g. secondary paraaortic dissection for pelvic pN1) will be evaluated in accordance with the NCI-CTCAE scale v4.03, until third year of post-operative follow-up. Adverse effects related to node dissection will be searched for, especially: - nervous complications (obturator, femoral nerves) - lymphatic (lymphocyst, leg lymphedema, erysipelas) complications. Concerning lymphocyst, only symptomatic lymphocysts (pain, fever...)

Secondary endpoints 6

1. In the experimental arm (SN policy), the overall detection rate of pelvic SN (uni- or bilateral) is calculated as the number of patients with at least one SN detected per-operatively, divided by the total number of patients who underwent staging in the experimental arm. Bilateral detection rate is calculated as number of patients with bilateral SN divided by the total number of patients who underwent staging.
2. SN-positive detection rate is calculated as number of detected SN divided by the total number of lymph nodes extracted
3. The disease free survival is defined as the time from the date of randomization to the first documentation of local, regional or distant relapse or all-cause death, whichever occurs first. Observations will be censored at the date of last follow-up for patients alive free of disease at last follow-up.
4. The overall survival is defined as the time from the date of randomization to the date of all-cause death. Observations will be censored at the date of last follow-up for patients still alive. The specific survival is defined as the time from the date of randomization to the date of death from cancer. Observations will be censored at the date of death for patients who died from another cause, and at the date of last follow-up for patients still alive.
5. Exploratory : standard staining with HES (hematoxylin-eosin-safran) is carried out in a systematic manner as well as immunohistochemistry with polyclonal anti-L1CAM: clone CD171 (SIGMA). The rate of L1CAM positive sample must be precised in the final pathology report, to be further correlated with the node involvement and disease recurrence.
6. Exploratory: Standard sections of SN, with IHC staining or not, are required for mass spectrometry analysis. For each tissue, 7 superfrost slides are needed with 2 or 3 sections by glass slide (depending to the size of the tissue). All SN slides must be stored by the investigational site until their transfer to PRISM laboratory. During the study, the sponsor will draft the list of samples to be analyzed, and will organize shipment of slides from the investigational site, to the PRISM laboratory.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Oscar Lambret

Sponsor organisation

Centre Oscar Lambret

Address

3 Rue Frederic Combemale

City

Lille

Postcode

59000

Country

France

Scientific contact point

Organisation

Centre Oscar Lambret

Contact name

Clinical Research Sponsor Unit

Public contact point

Organisation

Centre Oscar Lambret

Contact name

Clinical Research Sponsor Unit

Locations

1 EU/EEA country · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications