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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04073706




Registration number
NCT04073706
Ethics application status
Date submitted
26/08/2019
Date registered
29/08/2019
Date last updated
3/04/2025

Titles & IDs
Public title
Sentinel Node Biopsy in Endometrial Cancer
Scientific title
A Phase III Randomised Clinical Trial Comparing Sentinel Node Biopsy With No Retroperitoneal Node Dissection in Apparent Early-Stage Endometrial Cancer
Secondary ID [1] 0 0
ENDO-3
Universal Trial Number (UTN)
Trial acronym
ENDO-3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Endometrial Cancer Stage I 0 0
Sentinel Lymph Node 0 0
Surgery 0 0
Condition category
Condition code
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - 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
Treatment: Surgery - 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

Experimental: TH BSO with SNB - 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.

Active comparator: TH BSO without retroperitoneal node dissection - 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.


Treatment: Surgery: 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
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.

Treatment: Surgery: 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
Removal of uterus, tubes and ovaries without retroperitoneal node dissection
Intervention code [1] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Stage 1: Return to usual activities
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
12 months from surgery
Primary outcome [2] 0 0
Stage 2: Disease Free Survival
Assessment method [2] 0 0
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
Timepoint [2] 0 0
4.5 years from surgery
Secondary outcome [1] 0 0
Cost Effectiveness using QALYs using EuroQoL-5D (EQ-5D) Questionnaire
Assessment method [1] 0 0
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
Timepoint [1] 0 0
12 months from surgery
Secondary outcome [2] 0 0
Cost Effectiveness measuring Intervention costs
Assessment method [2] 0 0
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.
Timepoint [2] 0 0
12 months from surgery
Secondary outcome [3] 0 0
Cost Effectiveness measuring GP and specialist consultations
Assessment method [3] 0 0
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.
Timepoint [3] 0 0
12 months from surgery
Secondary outcome [4] 0 0
Cost Effectiveness measuring radiology and imaging requirements
Assessment method [4] 0 0
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.
Timepoint [4] 0 0
12 months from surgery
Secondary outcome [5] 0 0
Cost Effectiveness measuring prescriptions and over the counter medicine requirements
Assessment method [5] 0 0
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.
Timepoint [5] 0 0
12 months from surgery
Secondary outcome [6] 0 0
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
Assessment method [6] 0 0
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.
Timepoint [6] 0 0
12 months from surgery
Secondary outcome [7] 0 0
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
Assessment method [7] 0 0
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.
Timepoint [7] 0 0
12 months from surgery
Secondary outcome [8] 0 0
Perioperative Outcomes: Adverse Events
Assessment method [8] 0 0
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)
Timepoint [8] 0 0
12 months from surgery
Secondary outcome [9] 0 0
Perioperative Outcomes: Length of Surgery
Assessment method [9] 0 0
Compare the length of surgery between the two groups. This will be recorded in hh:mm on the surgery form.
Timepoint [9] 0 0
At time of surgery
Secondary outcome [10] 0 0
Perioperative Outcomes: Blood Loss during Surgery
Assessment method [10] 0 0
Compare the blood loss between the two groups during surgery. This will be recorded in ml.
Timepoint [10] 0 0
At time of surgery
Secondary outcome [11] 0 0
Perioperative Outcomes: Blood Transfusion Requirements during Surgery
Assessment method [11] 0 0
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.
Timepoint [11] 0 0
At time of surgery
Secondary outcome [12] 0 0
Perioperative Outcomes: Length of Hospital Stay
Assessment method [12] 0 0
Compare the length of hospital stay between the two groups. The duration will be measured in days. Date of surgery being day 0.
Timepoint [12] 0 0
At time of discharge from hospital following surgery
Secondary outcome [13] 0 0
Health Related Quality of Life and Fear of Recurrence
Assessment method [13] 0 0
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
Timepoint [13] 0 0
12 months from surgery
Secondary outcome [14] 0 0
Incidence of Lymphedema
Assessment method [14] 0 0
Compare lower limb lymphedema between groups
Timepoint [14] 0 0
12 months from surgery
Secondary outcome [15] 0 0
Adjuvant Treatment Requirements
Assessment method [15] 0 0
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.
Timepoint [15] 0 0
12 months from surgery
Secondary outcome [16] 0 0
Value of Molecular Biomarkers
Assessment method [16] 0 0
Translational Research - Compare Molecular profile from surgery between the groups that require adjuvant therapy for 24 months.
Timepoint [16] 0 0
24 months from surgery
Secondary outcome [17] 0 0
Value of Molecular Biomarkers
Assessment method [17] 0 0
Translational Research - Compare the Molecular profile of Germline DNA at 12 months from surgery between the groups
Timepoint [17] 0 0
12 months from surgery
Secondary outcome [18] 0 0
Value of Molecular Biomarkers
Assessment method [18] 0 0
Translational Research - Compare the Molecular profile of Circulating Tumour DNA at 12 months from surgery between the groups
Timepoint [18] 0 0
12 months from surgery
Secondary outcome [19] 0 0
Value of Molecular Biomarkers
Assessment method [19] 0 0
Translational Research - Compare the Molecular profile of Plasma at 12 months from surgery between the groups
Timepoint [19] 0 0
12 months from surgery
Secondary outcome [20] 0 0
Value of Molecular Biomarkers
Assessment method [20] 0 0
Translational Research - Compare the Molecular profile of Serum at 12 months from surgery between the groups
Timepoint [20] 0 0
12 months from surgery
Secondary outcome [21] 0 0
Overall Survival
Assessment method [21] 0 0
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
Timepoint [21] 0 0
4.5 years from surgery
Secondary outcome [22] 0 0
Patterns of Recurrence - date and localization of 1st recurrence
Assessment method [22] 0 0
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
Timepoint [22] 0 0
4.5 years from surgery
Secondary outcome [23] 0 0
Impact of body composition (sarcopenia) on surgical complications, recovery and overall survival
Assessment method [23] 0 0
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
Timepoint [23] 0 0
4.5 years from surgery
Secondary outcome [24] 0 0
Impact of frailty on surgical complications, recovery and overall survival
Assessment method [24] 0 0
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
Timepoint [24] 0 0
4.5 years from surgery
Secondary outcome [25] 0 0
Follow-Up Strategies
Assessment method [25] 0 0
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.
Timepoint [25] 0 0
4.5 years from surgery

Eligibility
Key inclusion criteria
1. Females, over 18 years, with histologically confirmed primary epithelial cancer of the endometrium of any cell type or uterine carcinosarcoma (mixed malignant mullerian tumour);
2. Clinically stage I disease (disease confined to body of uterus);
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
4. Signed written informed consent;
5. 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)
6. All available clinical evidence (physical examination findings, or medical imaging such as CT, MRI or ultrasound) demonstrates no evidence of extrauterine disease
7. 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).
8. Negative (serum or urine) pregnancy test = 30 days of surgery in pre-menopausal women and women < 2 years after the onset of menopause.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. 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.
2. Enlarged retroperitoneal pelvic and/or aortic lymph nodes (>1 cm) on medical imaging;
3. Estimated life expectancy of less than 6 months;
4. Patients who have absolute contraindications for adjuvant radiotherapy and/or chemotherapy;
5. Patients who have previously received radiation treatment to the pelvis
6. Serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator);
7. Patient compliance and geographic proximity that do not allow adequate follow-up;
8. Patients with allergy to Indocyanine Green (ICG)
9. Patients who have had previous retroperitoneal surgery
10. Patients who require a retroperitoneal (pelvic +/- para-aortic) lymph node dissection (lymphadenectomy)
11. Other prior malignancies <5 years before inclusion, except for successfully treated keratinocyte skin cancers, or ductal carcinoma of the breast insitu
12. Uterine perforation during endometrial tissue sampling

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/01/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/02/2031
Actual
Sample size
Target
760
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [3] 0 0
The Wesley Hospital - Auchenflower
Recruitment hospital [4] 0 0
Buderim Private Hospital - Buderim
Recruitment hospital [5] 0 0
North West Private Hospital - Everton Park
Recruitment hospital [6] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [7] 0 0
Mater Hospital - South Brisbane
Recruitment hospital [8] 0 0
Gold Coast University Hospital - Southport
Recruitment hospital [9] 0 0
St Andrews War Memorial Hospital - Spring Hill
Recruitment hospital [10] 0 0
Mercy Hospital for Women - Heidelberg
Recruitment hospital [11] 0 0
Royal Women's Hospital - Parkville
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2170 - Liverpool
Recruitment postcode(s) [3] 0 0
4066 - Auchenflower
Recruitment postcode(s) [4] 0 0
4556 - Buderim
Recruitment postcode(s) [5] 0 0
4053 - Everton Park
Recruitment postcode(s) [6] 0 0
4029 - Herston
Recruitment postcode(s) [7] 0 0
4101 - South Brisbane
Recruitment postcode(s) [8] 0 0
4215 - Southport
Recruitment postcode(s) [9] 0 0
4000 - Spring Hill
Recruitment postcode(s) [10] 0 0
3084 - Heidelberg
Recruitment postcode(s) [11] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Texas
Country [2] 0 0
Argentina
State/province [2] 0 0
Buenos Aires
Country [3] 0 0
Brazil
State/province [3] 0 0
Nelson De Sena
Country [4] 0 0
Brazil
State/province [4] 0 0
PR
Country [5] 0 0
Brazil
State/province [5] 0 0
Sao Paulo
Country [6] 0 0
Brazil
State/province [6] 0 0
SP
Country [7] 0 0
Colombia
State/province [7] 0 0
Medellin
Country [8] 0 0
India
State/province [8] 0 0
Delhi
Country [9] 0 0
Italy
State/province [9] 0 0
Via Pozzuolo
Country [10] 0 0
Singapore
State/province [10] 0 0
NUH Zone B

Funding & Sponsors
Primary sponsor type
Government body
Name
Queensland Centre for Gynaecological Cancer
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
The University of Queensland
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Andreas Obermiar, MD
Address 0 0
Director, Queensland Centre for Gynaecological Cancer Research
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Trial Manager
Address 0 0
Country 0 0
Phone 0 0
+61 7 3346 5590
Email 0 0
endo3trial@uq.edu.au
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT04073706