Endometrial Cancer Stage IPhase 3ENDO-3NCT04073706
Sentinel Node Biopsy in Endometrial Cancer
A Phase 3 study testing 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 and 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 in people with Endometrial Cancer Stage I and Sentinel Lymph Node, run by Queensland Centre for Gynaecological Cancer at 23 sites in 7 countries.
Trial 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)). Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Endometrial Cancer Stage I, Sentinel Lymph Node, Surgery
- What is being tested?
- 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 and 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
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 760 participants
- Where
- 23 sitesin 7 countries
- Study dates
- 18 Jan 2021to Feb 2031
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 ≤2;
- 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.
Who cannot join
- 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);
Show all 12Show fewer
- 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)
- Other prior malignancies <5 years before inclusion, except for successfully treated keratinocyte skin cancers, or ductal carcinoma of the breast insitu
- Uterine perforation during endometrial tissue sampling
Trial locations and contacts
23 sites in 7 countries. Contact the study team or a site near you to ask about taking part.
23 sites in 7 countries
Australia13 sites, 13 recruiting
- Recruiting
The Wesley Hospital
Auchenflower, Queensland, 4066
Grace Ngiam, +61 7 3346 5590, endo3trial@uq.edu.au
Sara Baniahmadi, +61 7 3346 5073, sara.baniahmadi@health.qld.gov.au
- Recruiting
Greenslopes Private Hospital
Brisbane, Queensland, 4120
Grace Ngiam, +61733465590, endo3trial@uq.edu.au
Sara Baniahmadi, +61733465073, sara.baniahmadi@health.qld.gov.au
- Recruiting
Buderim Private Hospital
Buderim, Queensland, 4556
Grace Ngiam, +61 7 3346 5590, endo3trial@uq.edu.au
Sara Baniahmadi, +61733465073, sara.baniahmadi@health.qld.gov.au
- Recruiting
Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050
Rhonda Farrell, MD, rhondafarrell@mac.com
Sadaf Kalam, sadaf.kalam@lh.org.au
- Recruiting
North West Private Hospital
Everton Park, Queensland, 4053
Grace Ngiam, 0733465590, endo3trial@uq.edu.au
Sara Baniahmadi, +61733465073, sara.baniahmadi@health.qld.gov.au
- Recruiting
Mercy Hospital for Women
Heidelberg, Victoria, 3084
Adam Pendlebury, MD, cgo@dradampendlebury.com.au
Carla Starmans, Cstarmans@mercy.com.au
- Recruiting
Royal Brisbane and Women's Hospital
Herston, Queensland, 4029
Grace Ngiam, +61 7 3346 5590, endo3trial@uq.edu.au
Sara Baniahmadi, +61733465073, sara.baniahmadi@health.qld.gov.au
- Recruiting
Liverpool Hospital
Liverpool, New South Wales, 2170
Michael Burling, MD, michael.burling@health.nsw.gov.au
Michael Burling, MD
- Recruiting
Epworth Freemasons
Melbourne, Victoria, 3002
Adam Pendlebury, MD, cgo@dradampendlebury.com.au
Adam Pendlebury, MD
- Recruiting
Royal Women's Hospital
Parkville, Victoria, 3052
Estefania Vicario, estefania.vicario@thewomens.org.au
Orla McNally, MD, Orla.McNally@thewomens.org.au
- Recruiting
Mater Hospital
South Brisbane, Queensland, 4101
Grace Ngiam, +61 7 3346 5590, endo3trial@uq.edu.au
Sara Baniahmadi, +61733465073, sara.baniahmadi@health.qld.gov.au
- Not yet recruiting
Gold Coast University Hospital
Southport, Queensland, 4215
Grace Ngiam, +61 7 3346 5590, endo3trial@uq.edu.au
Sara Baniahmadi, +61733465073, sara.baniahmadi@health.qld.gov.au
- Recruiting
St Andrews War Memorial Hospital
Spring Hill, Queensland, 4000
Grace Ngiam, +61 7 3346 5590, endo3trial@uq.edu.au
Sara Baniahmadi, +61733465073, sara.baniahmadi@health.qld.gov.au
Brazil3 sites, 3 recruiting
- Recruiting
Hospital de Base
São José do Rio Preto, São Paulo, 15090-000
Guilherme Accorsi, MD, dr.guilhermeaccorsi@gmail.com
Guilherme Accorsi, MD
- Recruiting
Fundacao Antonio Prudente, AC Camargo Cancer Center
São Paulo, São Paulo
Glauco Baiocchi Neto, MD, glauco.baiocchi@accamargo.org.br
Bruna Goncalves, bruna.goncalves@accamargo.org.br
- Recruiting
Hospital Israelita Albert Einstein
São Paulo, São Paulo
Renato Moretti-Marques, MD, morettimarques@gmail.com
Renato
Argentina2 sites, 2 recruiting
- Recruiting
Hospital Britanico
Buenos Aires, Ciudad Autónoma de Buenos Aires (caba)
Julian Di Guilmi, MD, Jdiguilmi@hbritanico.com.ar
Julian Di Guilmi, MD
- Recruiting
Hospital Italiano
Buenos Aires, Ciudad Autónoma de Buenos Aires (caba)
Diego Odetto, MD, diego.odetto@hospitalitaliano.org.ar
Diego Odetto, MD
Colombia2 sites, 2 recruiting
- Recruiting
Centro de tratamiento e investigación sobre Cáncer Luis Carlos Sarmiento Angulo
Bogotá, Bogotá, Distrito Capital, 110131
David Viveros, MD, dviverosc@gmail.com
Briegal De Las Calderon, bcalderon@fctic.org
- Not yet recruiting
Instituto de Cancerología S.A.S
Medellín, Antioquia, 050025
Gabriel Rendon, MD, gabriel.rendon@auna.org
Gabriel Rendon, MD
United States1 site, 1 recruiting
- Recruiting
Houston Methodist Hospital
Houston, Texas, 77030
Jaya Kamath, 713-441-6616, jskamath@houstonmethodist.org
Konny Fong, 346.238.5815, klchanfong@houstonmethodist.org
Italy1 site, 1 recruiting
- Recruiting
Azienda Sanitaria Universitaria Friuli Centrale (ASUFC)
Udine, Via Pozzuolo, 33100
Stefano Restaino, MD, stefano.restaino@asufc.sanita.fvg.it
Giuseppe Vizzielli, MD, giuseppe.vizzielli@asufc.sanita.fvg.it
Singapore1 site, 1 recruiting
- Recruiting
National University Hospital and National University Cancer Institute
Singapore, NUH Zone B, 119074
Joseph Ng Soon Yau, MD, obgnsyj@nus.edu.sg
Pearl S Tong, MD, pearl_sy_tong@nuhs.edu.sg
About this study
Official title: A Phase III Randomised Clinical Trial Comparing Sentinel Node Biopsy With No Retroperitoneal Node Dissection in Apparent Early-Stage Endometrial Cancer
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:
Read more
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.
Read the detailed description
Hypothesis: The primary hypothesis is that SNB will not cause detriment to patients (lymphoedema, morbidity, loss of quality of life) and not increase costs compared to patients without a retroperitoneal node dissection. The secondary hypothesis is that disease-free survival in patients without retroperitoneal node dissection is not inferior to those receiving SNB.
Aims: To determine the value of SNB for patients, the healthcare system and to exclude detriment to patients.
Objectives:
Primary Stage 1:
To determine the recovery of participants (defined as incidence of adverse events, lower limb lymphoedema and health-related QOL) and to the healthcare system (cost) of Sentinel Node Biopsy (SNB) for the surgical treatment of endometrial cancer.
Primary Stage 2:
Compare disease-free survival at 4.5 years for participants randomised to receive hysterectomy, bilateral salpingo-oophorectomy with SNB compared to participants randomised to hysterectomy, bilateral salpingo-oophorectomy without retroperitoneal node dissection.
Secondary:
- Compare patterns of recurrence and overall survival (OS) between the groups
- Determine the cost-effectiveness of SNB
- Compare Patient Reported Outcomes (PROMS) between the groups at 12 months from surgery
- Compare Health Related Quality of Life (HRQL) and Fear of Recurrence between the groups at 12 months from surgery
- Compare perioperative outcomes (duration of surgery, length of hospital stay, intraoperative blood loss, blood transfusion requirements) and the incidence of intra- and postoperative adverse events within 12 months from surgery between the groups
- Compare lower limb lymphoedema at 12 months after surgery
- Compare the need for postoperative (adjuvant) treatments between groups
- Determine the impact of body composition and frailty on survival, quality of life, lymphoedema, peri-, intra- and postoperative outcomes
- Compare follow-up strategies (clinical vs symptom checklist)
- Translational Research - Trans-ENDO 3 - biobanking strategy - Compare the Molecular profile at 12 months from surgery between the groups
- Conditions
- Endometrial Cancer Stage I, Sentinel Lymph Node, Surgery
- Being tested
- 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 Note: If participants (≤45yo), Grade 1 endometrial adenocarcinoma with myometrial invasion <50%, wish to retain their ovaries a BSO may be omitted
- Keywords
- uterine cancer, sentinel node biopsy
- Medical subject headings
- Endometrial Neoplasms, Uterine Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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 omittedProcedure or surgery
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 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 omittedProcedure or surgery
Removal of uterus, tubes and ovaries without retroperitoneal node dissection
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 4.5 years from surgery
Secondary outcomes (25)
Cost Effectiveness using QALYs using EuroQoL-5D (EQ-5D) Questionnaire
An assessment will be performed on the cost-effectiveness of TH + SNB relative to TH alone, calculated as the incremental cost per unit of improvement in functional outcome, measured in terms of the primary outcome. This will assess how much more money the proposed intervention will cost the health system and society, and whether this represents a sound investment in terms of the improvement in quality of life. We will also measure the quality-adjusted life years (QALYs) gained with the intervention and use this to undertake a cost-utility analysis. The QALY calculations will be based on health status measures for trial participants, with valuations of changes in health status and quality of life based on the EQ-5D
Measured: 12 months from surgery
Cost Effectiveness measuring Intervention costs
An assessment will be performed on the cost-effectiveness of TH + SNB relative to TH alone, calculated as the incremental cost per unit of improvement in functional outcome, measured in terms of the primary outcome. This will assess how much more money the proposed intervention will cost the health system and society.
Measured: 12 months from surgery
Cost Effectiveness measuring GP and specialist consultations
An assessment will be performed on the cost-effectiveness of TH + SNB relative to TH alone, calculated as the incremental cost per unit of improvement in functional outcome, measured in terms of the primary outcome. This will assess how much more money the proposed intervention will cost the health system and society, and whether this represents a sound investment in terms of the improvement in quality of life.
Measured: 12 months from surgery
Cost Effectiveness measuring radiology and imaging requirements
An assessment will be performed on the cost-effectiveness of TH + SNB relative to TH alone, calculated as the incremental cost per unit of improvement in functional outcome, measured in terms of the primary outcome. This will assess how much more money the proposed intervention will cost the health system and society.
Measured: 12 months from surgery
Cost Effectiveness measuring prescriptions and over the counter medicine requirements
An assessment will be performed on the cost-effectiveness of TH + SNB relative to TH alone, calculated as the incremental cost per unit of improvement in functional outcome, measured in terms of the primary outcome. This will assess how much more money the proposed intervention will cost the health system and society, and whether this represents a sound investment in terms of the improvement in quality of life.
Measured: 12 months from surgery
Cost Effectiveness measuring community and health service requirements and days off work and informal care required by family and friends using a combination of the Health Services Questionnaire and clinical files
An assessment will be performed on the cost-effectiveness of TH + SNB relative to TH alone, calculated as the incremental cost per unit of improvement in functional outcome, measured in terms of the primary outcome. This will assess how much more money the proposed intervention will cost the health system and society, and whether this represents a sound investment in terms of the improvement in quality of life.
Measured: 12 months from surgery
Cost Effectiveness: direct costs using a bottom-up approach by recording the volume of resource use in both groups of the trial, and then applying a unit cost to each component
Direct costs wukk be ibtained for smaples of participants, stratified by hospital, operation and outcome to assess the cost-effectiveness of TH + SNB relative to TH alone, calculated as the incremental cost per unit of improvement in functional outcome, measured in terms of the primary outcome. This will assess how much more money the proposed intervention will cost the health system and society.
Measured: 12 months from surgery
Perioperative Outcomes: Adverse Events
Compare perioperative outcomes and the incidence of intra- and postoperative adverse events within 12 months from surgery between groups using Common Terminology Criteria for Adverse Events (CTCAE version 5)
Measured: 12 months from surgery
Perioperative Outcomes: Length of Surgery
Compare the length of surgery between the two groups. This will be recorded in hh:mm on the surgery form.
Measured: At time of surgery
Perioperative Outcomes: Blood Loss during Surgery
Compare the blood loss between the two groups during surgery. This will be recorded in ml.
Measured: At time of surgery
Perioperative Outcomes: Blood Transfusion Requirements during Surgery
Compare the blood transfusion requirements between the two groups. This will be recorded in units and recorded on the Surgery Form and the Concomitant Medication Form.
Measured: At time of surgery
Perioperative Outcomes: Length of Hospital Stay
Compare the length of hospital stay between the two groups. The duration will be measured in days. Date of surgery being day 0.
Measured: At time of discharge from hospital following surgery
Health Related Quality of Life and Fear of Recurrence
Change in Quality of Life using Functional Assessment of Cancer General (FACT-EN), Fear of Recurrence and PROMS between baseline and 1 year after surgery
Measured: 12 months from surgery
Incidence of Lymphedema
Compare lower limb lymphedema between groups
Measured: 12 months from surgery
Adjuvant Treatment Requirements
Compare the need for postoperative (adjuvant) treatments between groups and evaluate the impact of SNB on clinical decisions regarding adjuvant treatment. Any chemotherapy or radiation therapy required will be recorded on specific chemotherapy or radiation forms. Chemotherapy will be recorded in mg received and number of doses required including start/end dates. Radiation treatment received will be recorded as total dose of Gy and how many fractions, including start and end dates.
Measured: 12 months from surgery
Value of Molecular Biomarkers
Translational Research - Compare Molecular profile from surgery between the groups that require adjuvant therapy for 24 months.
Measured: 24 months from surgery
Value of Molecular Biomarkers
Translational Research - Compare the Molecular profile of Germline DNA at 12 months from surgery between the groups
Measured: 12 months from surgery
Value of Molecular Biomarkers
Translational Research - Compare the Molecular profile of Circulating Tumour DNA at 12 months from surgery between the groups
Measured: 12 months from surgery
Value of Molecular Biomarkers
Translational Research - Compare the Molecular profile of Plasma at 12 months from surgery between the groups
Measured: 12 months from surgery
Value of Molecular Biomarkers
Translational Research - Compare the Molecular profile of Serum at 12 months from surgery between the groups
Measured: 12 months from surgery
Overall Survival
Compare overall 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
Measured: 4.5 years from surgery
Patterns of Recurrence - date and localization of 1st recurrence
Date and localization of 1st recurrence as confirmed histologically and/or radiologically - Compare these patterns of recurrences between the groups. These will also be adjudicated by an independent committee to ensure accuracy of documented recurrence
Measured: 4.5 years from surgery
Impact of body composition (sarcopenia) on surgical complications, recovery and overall survival
Body mass measures are practical \& sensitive for predicting health risks \& outcomes. Sarcopenia is defined as loss of skeletal muscle mass \& strength. It's been found to be associated with procedure-related morbidity, survival in cancer patients and increased use of healthcare. The concurrent appearance of low muscle mass with high adiposity (sarcopenic obesity) is common in people with chronic diseases. The trial will determine the role sarcopenia has on participants pre-operatively (via CT images \& Bioimpedance Spectroscopy (BIS - if available at site) \& postoperatively using the BIS in regard to survival in gynaecological malignancies, if it is a predictive factor for treatment adverse events \& participants tolerability of treatment \& compare diagnostic methods to determine medical fitness for surgery. BIS sends non-detectable electrical currents, at a range of frequencies through the body allowing precise measurement \& analysis of impedance to currents by extracellular fluid
Measured: 4.5 years from surgery
Impact of frailty on surgical complications, recovery and overall survival
It has been reported consistently that frailty has a significant impact on the occurrence of adverse postoperative outcomes. Therefore, measuring frailty is important to estimate risks, determine the best treatment options, and to aid diagnosis and care planning. Frailty will be measured prior to surgery suing the validated tool - Frailty Phenotype. This may determine the impact frailty has on survival, quality of life, lymphedema, peri-, intra- and postoperative outcomes
Measured: 4.5 years from surgery
Follow-Up Strategies
Current institutional \& clinical guidelines suggest patients need to be seen at regular follow up visits. The risk of developing a recurrence is higher within the initial period after surgery \& the majority of recurrences develop within those first 3 years. Participants will ideally be seen 3 monthly for the first 3 years \& 6 monthly until 4.5 years. The objective of follow up is that local recurrences from endometrial cancer are potentially curable. It helps to diagnose local recurrences as early as possible so that they are amenable for curative or effective palliative management. We will compare these clinical findings to a symptom checklist that will be completed by participants every 3 months from surgery until 4.5 years. This records patient reported symptoms that may indicate a recurrence. Comparing these findings should determine effective follow up strategies for this group of patients.
Measured: 4.5 years from surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2019
- Study start18 Jan 2021
- Primary completionJan 2031 (estimated)
- Study completionFeb 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Endometrial Cancer Stage IStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 760 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Queensland Centre for Gynaecological Cancer
- Sponsor type
- Other government
- Collaborators
- The University of Queensland
- Responsible party
- Sponsor
- Investigators
- Andreas Obermair, Prof, Study chair, Director, Queensland Centre for Gynaecological Cancer Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04073706
- Sponsor's protocol ID
- ENDO-3
- Acronym
- ENDO-3
- Status last verified
- Sep 2026
- First submitted
- 26 Aug 2019
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 34728527
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Randomised Clinical Trial Comparing Sentinel Node Biopsy With No Retroperitoneal Node Dissection in Apparent Early-Stage Endometrial Cancer
- ClinicalTrials.gov ID
- NCT04073706
- Acronym / sponsor ID
- ENDO-3 / ENDO-3
- Conditions
- Endometrial Cancer Stage I, Sentinel Lymph Node, Surgery
- Keywords
- uterine cancer, sentinel node biopsy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 760 participants (estimated)
- Lead sponsor
- Queensland Centre for Gynaecological CancerOther government
- Collaborators
- The University of Queensland
- Study start
- 18 Jan 2021 (actual)
- Primary completion
- Jan 2031 (estimated)
- Study completion
- Feb 2031 (estimated)
- First posted
- 29 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Hypothesis: The primary hypothesis is that SNB will not cause detriment to patients (lymphoedema, morbidity, loss of quality of life) and not increase costs compared to patients without a retroperitoneal node dissection. The secondary hypothesis is that disease-free survival in patients without retroperitoneal node dissection is not inferior to those receiving SNB.
Aims: To determine the value of SNB for patients, the healthcare system and to exclude detriment to patients.
Objectives:
Primary Stage 1:
To determine the recovery of participants (defined as incidence of adverse events, lower limb lymphoedema and health-related QOL) and to the healthcare system (cost) of Sentinel Node Biopsy (SNB) for the surgical treatment of endometrial cancer.
Primary Stage 2:
Compare disease-free survival at 4.5 years for participants randomised to receive hysterectomy, bilateral salpingo-oophorectomy with SNB compared to participants randomised to hysterectomy, bilateral salpingo-oophorectomy without retroperitoneal node dissection.
Secondary:
- Compare patterns of recurrence and overall survival (OS) between the groups
- Determine the cost-effectiveness of SNB
- Compare Patient Reported Outcomes (PROMS) between the groups at 12 months from surgery
- Compare Health Related Quality of Life (HRQL) and Fear of Recurrence between the groups at 12 months from surgery
- Compare perioperative outcomes (duration of surgery, length of hospital stay, intraoperative blood loss, blood transfusion requirements) and the incidence of intra- and postoperative adverse events within 12 months from surgery between the groups
- Compare lower limb lymphoedema at 12 months after surgery
- Compare the need for postoperative (adjuvant) treatments between groups
- Determine the impact of body composition and frailty on survival, quality of life, lymphoedema, peri-, intra- and postoperative outcomes
- Compare follow-up strategies (clinical vs symptom checklist)
- Translational Research - Trans-ENDO 3 - biobanking strategy - Compare the Molecular profile at 12 months from surgery between the groups
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TH BSO with SNB | Experimental | 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 omittedTotal 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. |
| TH BSO without retroperitoneal node dissection | Active comparator | 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 omittedTotal 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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 ≤2;
- 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)
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 omittedRemoval 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. | Procedure or surgery | 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 omittedRemoval of uterus, tubes and ovaries without retroperitoneal node dissection | Procedure or surgery | TH BSO without retroperitoneal node dissection |
Primary outcome
Stage 1: Return to usual activities
Time frame: 12 months from surgery
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.
Stage 2: Disease Free Survival
Time frame: 4.5 years from surgery
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
25 secondary outcomes
Cost Effectiveness using QALYs using EuroQoL-5D (EQ-5D) Questionnaire
Time frame: 12 months from surgery
Cost Effectiveness measuring Intervention costs
Time frame: 12 months from surgery
Cost Effectiveness measuring GP and specialist consultations
Time frame: 12 months from surgery
Cost Effectiveness measuring radiology and imaging requirements
Time frame: 12 months from surgery
Cost Effectiveness measuring prescriptions and over the counter medicine requirements
Time frame: 12 months from surgery
Cost Effectiveness measuring community and health service requirements and days off work and informal care required by family and friends using a combination of the Health Services Questionnaire and clinical files
Time frame: 12 months from surgery
Cost Effectiveness: direct costs using a bottom-up approach by recording the volume of resource use in both groups of the trial, and then applying a unit cost to each component
Time frame: 12 months from surgery
Perioperative Outcomes: Adverse Events
Time frame: 12 months from surgery
Perioperative Outcomes: Length of Surgery
Time frame: At time of surgery
Perioperative Outcomes: Blood Loss during Surgery
Time frame: At time of surgery
Perioperative Outcomes: Blood Transfusion Requirements during Surgery
Time frame: At time of surgery
Perioperative Outcomes: Length of Hospital Stay
Time frame: At time of discharge from hospital following surgery
Health Related Quality of Life and Fear of Recurrence
Time frame: 12 months from surgery
Incidence of Lymphedema
Time frame: 12 months from surgery
Adjuvant Treatment Requirements
Time frame: 12 months from surgery
Value of Molecular Biomarkers
Time frame: 24 months from surgery
Value of Molecular Biomarkers
Time frame: 12 months from surgery
Value of Molecular Biomarkers
Time frame: 12 months from surgery
Value of Molecular Biomarkers
Time frame: 12 months from surgery
Value of Molecular Biomarkers
Time frame: 12 months from surgery
Overall Survival
Time frame: 4.5 years from surgery
Patterns of Recurrence - date and localization of 1st recurrence
Time frame: 4.5 years from surgery
Impact of body composition (sarcopenia) on surgical complications, recovery and overall survival
Time frame: 4.5 years from surgery
Impact of frailty on surgical complications, recovery and overall survival
Time frame: 4.5 years from surgery
Follow-Up Strategies
Time frame: 4.5 years from surgery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2026.
- Derived from this study: PubMed 34728527Obermair 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Andreas Obermair, Prof study chair
Director, Queensland Centre for Gynaecological Cancer Research
23 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 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 and 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 in people with Endometrial Cancer Stage I and Sentinel Lymph Node, run by Queensland Centre for Gynaecological Cancer at 23 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in Australia, Brazil, Argentina, Colombia, United States and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Grace Ngiam (+61 7 3346 5590, endo3trial@uq.edu.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Stage 1: Return to usual activities (time frame: 12 months from surgery). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04073706, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2026.