Sentinel Node Biopsy in Endometrial Cancer

NCT04073706 | Recruiting Phase 3 DMC

• 1 other identifier: ENDO-3
• Study Type: interventional
• Target: 760
• Locations: 7 countries
• Sites: 19

Brief Summary

Endometrial cancer (EC) is the most common gynaecological cancer. Current treatment of EC typically includes removal of the uterus and to determine the extent of the disease (removal of fallopian tubes, ovaries \& if required a lymph node dissection (surgical staging)). While lymph node dissection may be valuable to guide the need for adjuvant treatment (chemo or radiotherapy) after surgery, it has been a topic of controversy for the last 30 years. In some patients it causes morbidity, specifically lymphoedema. This recently has been replaced with sentinel node biopsy (SNB). It requires an injection of a dye into the cervix with specific equipment \& surgical dissection of the lymph node in which the dye first becomes visible. Despite this promising proposition \& similar to a lymph node dissection, the value to patients, cost effectiveness \& potential harms (e.g. lymphedema) of SNB compared to no-node dissection in EC has never been established. Aim: determine the value of SNB for patients, the healthcare system and exclude detriment to patients using a randomised approach 1:1. Stage 1 - 444 patients. Stage 2 additional 316 patients. Primary Outcome Stage 1: Proportion of participants returning to usual daily activities at 12 months from surgery using the EQ-5D which will determine when women in both groups can return to their usual activities. Primary Outcome Stage 2: Treatment non-inferiority as evaluated by disease-free survival status at 4.5 years post-surgery, as measured by the time interval between the date of randomisation and date of first recurrence. Confirmation of recurrent disease will be ascertained through clinical assessment, radiological work-up and/or histological results.

Conditions

Sentinel Lymph Node; Surgery; Endometrial Cancer Stage I

Keywords

uterine cancer; sentinel node biopsy

Outcome Measures

Primary Outcomes (2)

• Stage 1: Return to usual activities

  Proportion of participants returning to usual daily activities at 12 months from surgery using the EQ-5D which will determine when women in both groups can return to their usual activities.

  12 months from surgery

• Stage 2: Disease Free Survival

  Compare disease-free survival for participants randomised to receive hysterectomy, bilateral salpingo-oophorectomy with SNB compared to participants randomised to hysterectomy, bilateral salpingo-oophorectomy without retroperitoneal node dissection

  4.5 years from surgery

Secondary Outcomes (25)

• Cost Effectiveness using QALYs using EuroQoL-5D (EQ-5D) Questionnaire

  12 months from surgery

• Cost Effectiveness measuring Intervention costs

  12 months from surgery

• Cost Effectiveness measuring GP and specialist consultations

  12 months from surgery

• Cost Effectiveness measuring radiology and imaging requirements

  12 months from surgery

• Cost Effectiveness measuring prescriptions and over the counter medicine requirements

  12 months from surgery

Study Arms (2)

TH BSO with SNB

EXPERIMENTAL

Total Laparoscopic/Robotic Hysterectomy, Bilateral Salpingo-Oophorectomy (TH BSO) with Sentinel Node Biopsy (SNB) using Indocyanine Green (ICG)+/- Methylene Blue Dye (+/- omentectomy in high risk cell types) Note: If participants (≤45 years of age), have Grade 1 endometrial adenocarcinoma (EAC) with myometrial invasion \<50% (by MRI) and wish to retain their ovaries a BSO may be omitted.

Procedure: TH BSO with SNB Note: If participants (≤45yo), Grade 1 endometrial adenocarcinoma with myometrial invasion <50%, wish to retain their ovaries a BSO may be omitted

TH BSO without retroperitoneal node dissection

ACTIVE COMPARATOR

Total Laparoscopic/Robotic Hysterectomy, Bilateral Salpingo-Oophorectomy (TH BSO) without retroperitoneal node dissection (+/- omentectomy in high risk cell types) Note: If participants (≤45 years of age), have Grade 1 endometrial adenocarcinoma (EAC) with myometrial invasion \<50% (by MRI) and wish to retain their ovaries a BSO may be omitted.

Procedure: TH BSO without retroperitoneal node dissection Note: If participants (≤45yo), Grade 1 endometrial adenocarcinoma with myometrial invasion <50%, wish to retain their ovaries a BSO may be omitted

Interventions

TH BSO with SNB Note: If participants (≤45yo), Grade 1 endometrial adenocarcinoma with myometrial invasion <50%, wish to retain their ovaries a BSO may be omitted PROCEDURE

Removal of uterus, tubes and ovaries with a sentinel node biopsy. A tracer dye (ICG) +/- Methylene Blue Dye is injected into the surroundings of the primary tumour, it is transported via local lymphatic channels towards the draining lymphatic basin, and the first node that the tracer reaches is called the "sentinel node". These one or two nodes are thought to be first involved with cancer spread.

TH BSO with SNB

TH BSO without retroperitoneal node dissection Note: If participants (≤45yo), Grade 1 endometrial adenocarcinoma with myometrial invasion <50%, wish to retain their ovaries a BSO may be omitted PROCEDURE

Removal of uterus, tubes and ovaries without retroperitoneal node dissection

TH BSO without retroperitoneal node dissection

Eligibility Criteria

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

You may qualify if:

• Females, over 18 years, with histologically confirmed primary epithelial cancer of the endometrium of any cell type or uterine carcinosarcoma (mixed malignant mullerian tumour);
• Clinically stage I disease (disease confined to body of uterus);
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• Signed written informed consent;
• Participant must meet criteria for a laparoscopic or robotic surgical approach as determined by the treating physician (e.g. suitable for TH BSO, ability to tolerate Trendelenberg positioning)
• All available clinical evidence (physical examination findings, or medical imaging such as CT, MRI or ultrasound) demonstrates no evidence of extrauterine disease
• Myometrial Invasion on MRI of not more than 50%. (Only if participant is \<45yo, has ONLY Grade 1 EAC and wishes to retain their ovaries).
• Negative (serum or urine) pregnancy test ≤ 30 days of surgery in pre-menopausal women and women \< 2 years after the onset of menopause.

You may not qualify if:

• Evidence of extrauterine disease (apparent involvement of cervix, vagina, parametria, adnexa, lymph nodes, bladder, bowel or distant sites) by clinical examination and/or through medical imaging.
• Enlarged retroperitoneal pelvic and/or aortic lymph nodes (\>1 cm) on medical imaging;
• Estimated life expectancy of less than 6 months;
• Patients who have absolute contraindications for adjuvant radiotherapy and/or chemotherapy;
• Patients who have previously received radiation treatment to the pelvis
• Serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator);
• Patient compliance and geographic proximity that do not allow adequate follow-up;
• Patients with allergy to Indocyanine Green (ICG)
• Patients who have had previous retroperitoneal surgery
• Patients who require a retroperitoneal (pelvic +/- para-aortic) lymph node dissection (lymphadenectomy)
• Uterine perforation during endometrial tissue sampling

Sponsors & Collaborators

• The University of Queensland: collaborator
• Queensland Centre for Gynaecological Cancer: lead

Study Sites (19)

Houston Methodist Hospital

Houston, Texas, 77030, United States

RECRUITING

Hospital Britanico

Buenos Aires, Ciudad Autónoma de Buenos Aires (caba), Argentina

NOT YET RECRUITING

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

RECRUITING

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

RECRUITING

The Wesley Hospital

Auchenflower, Queensland, 4066, Australia

RECRUITING

Buderim Private Hospital

Buderim, Queensland, 4556, Australia

RECRUITING

North West Private Hospital

Everton Park, Queensland, 4053, Australia

RECRUITING

Royal Brisbane and Women's Hospital

Herston, Queensland, 4029, Australia

RECRUITING

Mater Hospital

South Brisbane, Queensland, 4101, Australia

RECRUITING

Gold Coast University Hospital

Southport, Queensland, 4215, Australia

NOT YET RECRUITING

St Andrews War Memorial Hospital

Spring Hill, Queensland, 4000, Australia

RECRUITING

Mercy Hospital for Women

Heidelberg, Victoria, 3084, Australia

RECRUITING

Royal Women's Hospital

Parkville, Victoria, 3052, Australia

RECRUITING

Hospital de Base

São José do Rio Preto, São Paulo, 15090-000, Brazil

RECRUITING

Fundacao Antonio Prudente, AC Camargo Cancer Center

São Paulo, São Paulo, Brazil

RECRUITING

Hospital Israelita Albert Einstein

São Paulo, São Paulo, Brazil

NOT YET RECRUITING

Centro de tratamiento e investigación sobre Cáncer Luis Carlos Sarmiento Angulo

Bogotá, Bogotá, Distrito Capital, 110131, Colombia

RECRUITING

Azienda Sanitaria Universitaria Friuli Centrale (ASUFC)

Udine, Via Pozzuolo, 33100, Italy

RECRUITING

National University Hospital and National University Cancer Institute

Singapore, NUH Zone B, 119074, Singapore

RECRUITING

Related Publications (1)

• Obermair A, Nicklin J, Gebski V, Hayes SC, Graves N, Mileshkin L, Lin MY, Beale P, Baxter E, Robledo K, Salomon C, Hanna GB, Janda M. A phase III randomized clinical trial comparing sentinel node biopsy with no retroperitoneal node dissection in apparent early-stage endometrial cancer - ENDO-3: ANZGOG trial 1911/2020. Int J Gynecol Cancer. 2021 Dec;31(12):1595-1601. doi: 10.1136/ijgc-2021-003029. Epub 2021 Nov 2.

  PMID: 34728527 DERIVED

MeSH Terms

Conditions

Endometrial Neoplasms; Uterine Neoplasms

Condition Hierarchy (Ancestors)

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

• Andreas Obermair, Prof

  Director, Queensland Centre for Gynaecological Cancer Research

  STUDY CHAIR

Central Study Contacts

Grace Ngiam

CONTACT

+61 7 3346 5590; endo3trial@uq.edu.au

Sara Baniahmadi

CONTACT

+61733465073; sara.baniahmadi@health.qld.gov.au

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2019
• First Posted: August 29, 2019
• Study Start: January 18, 2021
• Primary Completion (Estimated): January 1, 2031
• Study Completion (Estimated): February 1, 2031
• Last Updated: January 30, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CO (1); US (1); AR (1); AU (11); BR (3); SG (1); IT (1)