A Prospective Study Comparing Three Injection Sites to Detect Sentinel Lymph Nodes in Endometrial Cancer

NCT04577950 | Unknown DMC

• 1 other identifier: SENNAN
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Uterine cancer is the most common gynecologic malignancy in developed countries. Adenocarcinoma of the endometrium is the most common histologic type of uterine cancer. Endometrial cancer is the fifth most frequent cancer in women in Switzerland. The incidence rose up to 5.9% in 2015. This tumor affects mainly older women, at 63 years on average. The majority of women are diagnosed at an early stage. Seventy-five to 90% of the patients are alerted by abnormal uterine bleeding very quickly, which allows a quick management of care and a high survival rate. Besides age, one of the main risk factor of developing an endometrial carcinoma is obesity. In fact, obese women have higher risk to have an endometrial cancer, but also at a younger age than the average and finally they have an increased risk of death due to this particular cancer. Although this cancer is linked to the co-morbidities that go with obesity like diabetes or hypertension. The treatment of endometrial cancer in most women is surgery involving a total hysterectomy and a bilateral salpingo-oophorectomy with or without a lymph node dissection. For patients with early stage endometrial cancer, there is a disagreement regarding lymph nodes dissection, because randomized controlled trials and a meta-analysis have shown no clear evidence on overall or recurrence-free survival and a higher incidence on early and late complications in relation with pelvic lymph node dissection. A systematic lymph node dissection consists of removing all the nodes within a nodal drainage basin. This dissection proves to be very difficult in obese patient and includes a risk to damage blood vessels or nerves. Moreover, lymph node dissection is associated with a higher morbidity, longer operating time, more frequent blood loss and finally symptomatic lymphedema and seroma. That is why, sentinel lymph node biopsy (SLNB) seems to be a good alternative to lymph node dissection. The tumor's spread is assessed in lymph nodes with a reduced morbidity. In fact, lymphadenectomy and its dangerous complications, like lymphedema, could be avoided in the vast majority of cases. Indeed, a histological analysis of these sentinel lymph-nodes (SLNs) leads to ultrastadification: cancers are graded depending on the presence and the size of metastasis in lymph nodes. Adjuvant treatments, such as radiotherapy or chemotherapy, can be suggested following these data and a better management of endometrial cancer is possible.

Conditions

Endometrial Cancer

Keywords

Sentinel node; Endometrial carcinoma; Lymphatic drainage

Outcome Measures

Primary Outcomes (1)

• Lymphatic route of endometrial cancer dissemination

  Comparing the per-operative anatomical locations of uterine SLNs depending on the 3 different injection sites of the tracers: whether in endometrium, in uterine isthmus or in the cervix.

  1 month

Secondary Outcomes (9)

• Sensibility/sensitivity of the tracers

  1 month

• Adverse events

  1 month

• Additional time required to identify SLNs

  1 month

• Morbidity directly induced by the search of SLNs

  1 month

• Negative predictive value of the different markers

  1 month

Study Arms (1)

Arm with procedure: identification of lymphatic drainage of the uterus following 3 sites injections

EXPERIMENTAL

A radiocolloid (Nanocoll® marked with Technetium 99), a fluorochrome (ICG) and a blue dye (Bleu Patenté®) will be injected in submucosal tissue to see the differences in lymphatic drainage between three different injection sites. Indeed, ICG will be injected under the endometrium, whereas Nanocoll® will be injected in the cervix and Bleu Patenté® in the uterine isthmus, at the transition between the cervix and the uterine corpus.

Procedure: Lymphatic drainage of endometrial cancer

Interventions

Lymphatic drainage of endometrial cancer PROCEDURE

Nanocoll® is injected a day before surgery in the cervix at four points. A lymphoscintigraphy is performed 2 or 3 hours afterward. At the beginning of the surgery, the operative field already in place and before the beginning of laparoscopic, 2ml (10mg) of ICG, distributed in four points around the tumor, is injected under the endometrium intra-myometrial under endoscopic control. As ICG spreads slower than blue dye, ICG is always injected first. Then, Bleu Patenté® is injected at two sites in the uterine isthmus, opposite of the uterine arteries. The risk of false negative results, because a tracer migrated too quickly, is reduced when the injection takes place when patients are already anesthetized.

Arm with procedure: identification of lymphatic drainage of the uterus following 3 sites injections

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed Consent as documented by signature
• Early endometrial cancers (of International Federation of Gynecology and Obstetrics stage IA-IB), whatever histological grade and type
• Primary surgical treatment with hysterectomy
• No metastasis, no other cancers, no recurrency of cancers
• No signs of lymph nodes metastasis on the preoperative workup (MRI +/- positron emission computed tomography)
• No contraindication to laparoscopic procedures.
• Women of \> 18 years

You may not qualify if:

• Known severe allergies (antecedents of Quincke oedema, anaphylactic shock,…) and a history of allergy to iodides
• Contraindications to the injected products because of known hypersensitivity or allergy to ICG of blue dye
• Antecedent of pelvic lymph nodes surgery
• Previous lymphadenectomy or surgery that could change the uterine lymphatic drainage (conisation or myomectomy)
• Other diagnosed cancer during treatment or care
• Stage II and above (tumor invading cervix stroma) including those after a neo-adjuvant treatment
• Suspicion of lymph nodes metastasis at preoperative workup
• Medical or uterine conservative treatment
• Patient, who does not understand, speak or write in French
• Drugs that can interfere with ICG : anti convulsants - bisulphite compounds - haloperidol - heroin - pethidine \[meperidine\] - methamizole - methadone - morphine - nitrofurantoin - opium alkaloids - phenobarbitone- phenylbutazone - cyclopropane - probenecid - rifamycin - sodium bisulphite (mostly combined with heparin)
• Radioactive iodine uptake performed less than one week following the use of ICG.
• Hypersensitivity to Nanocoll, to any of the excipients (Stannous chloride, dihydrate Glucose, anhydrous Poloxamer 238 Sodium phosphate, dibasic, anhydrous Sodium phytate, anhydrous) or to any of the components of the labelled radiopharmaceutical.
• A history of hypersensitivity to products containing human albumin
• Hypersensitivity to dyes made of triphenylmethane
• Lymphostasis

Sponsors & Collaborators

• Centre Hospitalier Universitaire Vaudois: lead

Study Sites (1)

CHUV department of gynecology

Lausanne, 1011, Switzerland

RECRUITING

MeSH Terms

Conditions

Endometrial Neoplasms

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Patrice Mathevet, MD - PhD

  Centre Hospitalier Universitaire Vaudois

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Patrice Mathevet, MD- PhD

CONTACT

+41213146727; patrice.mathevet@chuv.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of the gynecologic department

Model Details: A prospective phase 2 study comparing three injection sites to detect sentinel lymph nodes in endometrial cancer.

Study Record Dates

• First Submitted: September 12, 2020
• First Posted: October 8, 2020
• Study Start: January 21, 2021
• Primary Completion: September 1, 2024
• Study Completion: December 1, 2024
• Last Updated: January 27, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: 3 years
• Access Criteria: Request to PI

Locations

CH (1)