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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT04073706
Registration number
NCT04073706
Ethics application status
Date submitted
26/08/2019
Date registered
29/08/2019
Date last updated
26/03/2024
Titles & IDs
Public title
Sentinel Node Biopsy in Endometrial Cancer
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Scientific title
A Phase III Randomised Clinical Trial Comparing Sentinel Node Biopsy With No Retroperitoneal Node Dissection in Apparent Early-Stage Endometrial Cancer
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Secondary ID [1]
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ENDO-3
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Universal Trial Number (UTN)
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Trial acronym
ENDO-3
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Endometrial Cancer Stage I
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Sentinel Lymph Node
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Surgery
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Condition category
Condition code
Cancer
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Womb (Uterine or endometrial cancer)
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Intervention/exposure
Study type
Interventional
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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
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Intervention code [1]
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Treatment: Surgery
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Stage 1: Return to usual activities
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Assessment method [1]
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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.
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Timepoint [1]
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12 months from surgery
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Primary outcome [2]
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Stage 2: Disease Free Survival
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Assessment method [2]
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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
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Timepoint [2]
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4.5 years from surgery
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Secondary outcome [1]
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Cost Effectiveness using QALYs using EuroQoL-5D (EQ-5D) Questionnaire
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Assessment method [1]
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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
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Timepoint [1]
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12 months from surgery
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Secondary outcome [2]
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Cost Effectiveness measuring Intervention costs
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Assessment method [2]
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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.
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Timepoint [2]
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12 months from surgery
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Secondary outcome [3]
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Cost Effectiveness measuring GP and specialist consultations
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Assessment method [3]
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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.
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Timepoint [3]
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12 months from surgery
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Secondary outcome [4]
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Cost Effectiveness measuring radiology and imaging requirements
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Assessment method [4]
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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.
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Timepoint [4]
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12 months from surgery
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Secondary outcome [5]
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Cost Effectiveness measuring prescriptions and over the counter medicine requirements
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Assessment method [5]
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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.
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Timepoint [5]
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12 months from surgery
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Secondary outcome [6]
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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
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Assessment method [6]
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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.
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Timepoint [6]
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12 months from surgery
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Secondary outcome [7]
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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
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Assessment method [7]
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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.
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Timepoint [7]
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12 months from surgery
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Secondary outcome [8]
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Perioperative Outcomes: Adverse Events
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Assessment method [8]
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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)
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Timepoint [8]
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12 months from surgery
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Secondary outcome [9]
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Perioperative Outcomes: Length of Surgery
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Assessment method [9]
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Compare the length of surgery between the two groups. This will be recorded in hh:mm on the surgery form.
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Timepoint [9]
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At time of surgery
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Secondary outcome [10]
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Perioperative Outcomes: Blood Loss during Surgery
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Assessment method [10]
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Compare the blood loss between the two groups during surgery. This will be recorded in ml.
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Timepoint [10]
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At time of surgery
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Secondary outcome [11]
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Perioperative Outcomes: Blood Transfusion Requirements during Surgery
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Assessment method [11]
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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.
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Timepoint [11]
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At time of surgery
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Secondary outcome [12]
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Perioperative Outcomes: Length of Hospital Stay
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Assessment method [12]
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Compare the length of hospital stay between the two groups. The duration will be measured in days. Date of surgery being day 0.
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Timepoint [12]
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At time of discharge from hospital following surgery
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Secondary outcome [13]
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Health Related Quality of Life and Fear of Recurrence
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Assessment method [13]
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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
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Timepoint [13]
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12 months from surgery
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Secondary outcome [14]
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Incidence of Lymphedema
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Assessment method [14]
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Compare lower limb lymphedema between groups
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Timepoint [14]
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12 months from surgery
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Secondary outcome [15]
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Adjuvant Treatment Requirements
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Assessment method [15]
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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.
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Timepoint [15]
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12 months from surgery
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Secondary outcome [16]
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Value of Molecular Biomarkers
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Assessment method [16]
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Translational Research - Compare Molecular profile from surgery between the groups that require adjuvant therapy for 24 months.
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Timepoint [16]
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24 months from surgery
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Secondary outcome [17]
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Value of Molecular Biomarkers
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Assessment method [17]
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Translational Research - Compare the Molecular profile of Germline DNA at 12 months from surgery between the groups
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Timepoint [17]
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12 months from surgery
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Secondary outcome [18]
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Value of Molecular Biomarkers
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Assessment method [18]
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Translational Research - Compare the Molecular profile of Circulating Tumour DNA at 12 months from surgery between the groups
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Timepoint [18]
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12 months from surgery
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Secondary outcome [19]
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Value of Molecular Biomarkers
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Assessment method [19]
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Translational Research - Compare the Molecular profile of Plasma at 12 months from surgery between the groups
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Timepoint [19]
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12 months from surgery
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Secondary outcome [20]
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Value of Molecular Biomarkers
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Assessment method [20]
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Translational Research - Compare the Molecular profile of Serum at 12 months from surgery between the groups
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Timepoint [20]
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12 months from surgery
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Secondary outcome [21]
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Overall Survival
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Assessment method [21]
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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
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Timepoint [21]
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4.5 years from surgery
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Secondary outcome [22]
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Patterns of Recurrence - date and localization of 1st recurrence
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Assessment method [22]
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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
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Timepoint [22]
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4.5 years from surgery
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Secondary outcome [23]
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Impact of body composition (sarcopenia) on surgical complications, recovery and overall survival
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Assessment method [23]
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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
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Timepoint [23]
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4.5 years from surgery
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Secondary outcome [24]
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Impact of frailty on surgical complications, recovery and overall survival
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Assessment method [24]
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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
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Timepoint [24]
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4.5 years from surgery
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Secondary outcome [25]
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Follow-Up Strategies
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Assessment method [25]
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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.
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Timepoint [25]
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4.5 years from surgery
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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.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Females
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Can healthy volunteers participate?
No
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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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
18/01/2021
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
1/01/2031
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Actual
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Sample size
Target
760
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS,VIC
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Recruitment hospital [1]
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Chris O'Brien Lifehouse - Camperdown
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Recruitment hospital [2]
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St George Hospital - Kogarah
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Recruitment hospital [3]
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The Wesley Hospital - Auchenflower
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Recruitment hospital [4]
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Buderim Private Hospital - Buderim
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Recruitment hospital [5]
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Townsville Hospital - Douglas
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Recruitment hospital [6]
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North West Private Hospital - Everton Park
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Recruitment hospital [7]
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Royal Brisbane and Women's Hospital - Herston
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Recruitment hospital [8]
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Mater Hospital - South Brisbane
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Recruitment hospital [9]
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Gold Coast University Hospital - Southport
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Recruitment hospital [10]
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St Andrews War Memorial Hospital - Spring Hill
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Recruitment hospital [11]
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Royal Hobart Hospital - Hobart
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Recruitment hospital [12]
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Mercy Hospital for Women - Heidelberg
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Recruitment hospital [13]
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Royal Women's Hospital - Parkville
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Recruitment postcode(s) [1]
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2050 - Camperdown
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Recruitment postcode(s) [2]
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2217 - Kogarah
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Recruitment postcode(s) [3]
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4066 - Auchenflower
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Recruitment postcode(s) [4]
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4556 - Buderim
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Recruitment postcode(s) [5]
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4814 - Douglas
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Recruitment postcode(s) [6]
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4053 - Everton Park
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Recruitment postcode(s) [7]
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4029 - Herston
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Recruitment postcode(s) [8]
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4101 - South Brisbane
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Recruitment postcode(s) [9]
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4215 - Southport
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Recruitment postcode(s) [10]
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4000 - Spring Hill
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Recruitment postcode(s) [11]
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7000 - Hobart
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Recruitment postcode(s) [12]
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3084 - Heidelberg
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Recruitment postcode(s) [13]
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3052 - Parkville
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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Texas
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Country [2]
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Brazil
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State/province [2]
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Sao Paulo
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Country [3]
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India
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State/province [3]
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Delhi
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Country [4]
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Singapore
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State/province [4]
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NUH Zone B
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Funding & Sponsors
Primary sponsor type
Other
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Name
Queensland Centre for Gynaecological Cancer
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Address
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Country
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Other collaborator category [1]
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Other
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Name [1]
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The University of Queensland
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Address [1]
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Country [1]
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Ethics approval
Ethics application status
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Summary
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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT04073706
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Andreas Obermiar, MD
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Address
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Director, Queensland Centre for Gynaecological Cancer Research
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Vanessa Behan, BSN
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Address
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Country
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Phone
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+61 7 3346 5590
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Fax
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Email
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[email protected]
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT04073706
Download to PDF