Sentinel Node Biopsy for Endometrial Cancer

(ENDO-3 Trial)

Recruiting at 26 trial locations

Overseen By Trial Manager

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Queensland Centre for Gynaecological Cancer

Disqualifiers: Extrauterine disease, Enlarged lymph nodes, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

760 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Sentinel Node Biopsy for Endometrial Cancer?

Research shows that Sentinel Node Biopsy (SLNB) is effective in detecting cancer spread in endometrial cancer patients, helping to avoid more invasive surgeries like full lymph node removal. Studies indicate that SLNB can accurately identify cancerous nodes, which is crucial for tailoring further treatment and improving patient outcomes. ^{1 2 3 4 5}

Is sentinel node biopsy generally safe for humans?

Sentinel node biopsy (SLNB) is considered a minimally invasive procedure and is used to reduce surgical complications compared to full lymph node removal, suggesting it is generally safe for humans. ^{3 6 7 8 9}

How is the treatment Sentinel Node Biopsy different from other treatments for endometrial cancer?

Sentinel Node Biopsy is a surgical technique that targets only the first few lymph nodes (sentinel nodes) to check for cancer spread, unlike complete lymph node removal, which involves taking out many nodes. This approach can reduce surgical complications and is particularly useful in early-stage endometrial cancer. ^{1 10 11 12 13}

Research Team

Andreas Obermiar, MD

Principal Investigator

Director, Queensland Centre for Gynaecological Cancer Research

Eligibility Criteria

This trial is for women over 18 with early-stage endometrial cancer, confirmed by tissue analysis. They should be physically able to undergo laparoscopic or robotic surgery and have no signs of cancer outside the uterus. Women under 45 wishing to keep their ovaries can join if they have a specific low-grade tumor with limited invasion.

Inclusion Criteria

My doctor approves me for surgery using a robot or through small cuts.

I am fully active or can carry out light work.

Negative (serum or urine) pregnancy test ≤ 30 days of surgery in pre-menopausal women and women < 2 years after the onset of menopause.

Exclusion Criteria

Estimated life expectancy of less than 6 months

Patient compliance and geographic proximity that do not allow adequate follow-up

Patients with allergy to Indocyanine Green (ICG)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Participants undergo Total Laparoscopic/Robotic Hysterectomy, Bilateral Salpingo-Oophorectomy with or without Sentinel Node Biopsy

At time of surgery

Recovery and Initial Follow-up

Participants are monitored for recovery, adverse events, and return to usual activities

12 months

Regular follow-up visits as per institutional guidelines

Long-term Follow-up

Participants are monitored for disease-free survival and recurrence

4.5 years

3 monthly visits for the first 3 years, then 6 monthly until 4.5 years

Treatment Details

Interventions

• Sentinel Node Biopsy

Trial Overview The study compares traditional surgical removal of reproductive organs in endometrial cancer patients with and without sentinel node biopsy (SNB), which uses dye to identify key lymph nodes for removal. The aim is to see if SNB can replace more extensive surgery without compromising patient outcomes.

Participant Groups

Group I: TH BSO with SNB Experimental Treatment 1 Intervention

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.

Group II: TH BSO without retroperitoneal node dissection Active Control 1 Intervention

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.

Sentinel Node Biopsy is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Sentinel Lymph Node Biopsy for:

• Endometrial cancer
• Breast cancer
• Melanoma

Approved in United States as Sentinel Lymph Node Biopsy for:

• Endometrial cancer
• Breast cancer
• Melanoma
• Penile cancer

Approved in Canada as Sentinel Lymph Node Biopsy for:

• Endometrial cancer
• Breast cancer
• Melanoma

Who Is Running the Clinical Trial?

Queensland Centre for Gynaecological Cancer

Lead Sponsor

Trials

17

Recruited

5,100+

The University of Queensland

Collaborator

Trials

149

Recruited

71,700+

Findings from Research

In a study of 301 patients with early-stage endometrial carcinoma, sentinel lymph node (SLN) biopsy was found to have similar oncological outcomes in terms of progression-free survival and overall survival compared to complete lymph node dissection, indicating its effectiveness as a less invasive option.

The SLN biopsy group experienced significantly shorter surgical durations, suggesting that this method may reduce surgical risks and recovery time without compromising cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of oncological outcomes between sentinel lymph node biopsy and complete lymphadenectomy for endometrial cancer. Makroum, AA., Lee, YJ., Lee, JY., et al.[2023]

In a study of 74 patients with endometrial cancer, sentinel lymph node (SLN) mapping was successfully achieved in 62.1% of cases, with detection rates improving significantly from 50% to 84.6% after the first 30 cases, indicating that surgeon experience plays a crucial role in the success of this technique.

The use of methylene blue dye resulted in a higher detection rate (74.3%) compared to patent blue dye (52.3%), and factors such as high body mass index (BMI) and lymph-vascular space invasion (LVSI) were associated with lower success rates in SLN mapping.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robotic blue-dye sentinel lymph node detection for endometrial cancer - Factors predicting successful mapping. Eitan, R., Sabah, G., Krissi, H., et al.[2015]

In a study of 88 patients with intermediate- and high-risk endometrial cancer, sentinel lymph node biopsy (SLNB) demonstrated a high detection rate of 96.6%, allowing for effective identification of nodal metastases, particularly low volume metastasis (LVM).

The results suggest that SLNB can potentially replace full lymphadenectomy in intermediate-risk patients due to its high sensitivity (90%) and negative predictive value (97.5%), while for high-risk patients, full lymph node dissection may still be necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avoiding Full Lymphadenectomies in Intermediate- and High-Risk Endometrial Cancer by Sentinel Lymph Node Biopsy Implementation. Pineda, VG., Zapardiel, I., Gracia, M., et al.[2022]

The sentinel lymph node (SLN) biopsy demonstrated a high sensitivity of 93.7% for detecting nodal disease in a study of 892 patients with early-stage endometrial adenocarcinoma, indicating its effectiveness in clinical settings.

Patients with macrometastases had significantly lower overall and disease-free survival rates compared to those with negative nodes or low-volume disease, highlighting the importance of accurate staging for tailoring adjuvant treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accuracy and Survival Outcomes after National Implementation of Sentinel Lymph Node Biopsy in Early Stage Endometrial Cancer. Cabrera, S., Gómez-Hidalgo, NR., García-Pineda, V., et al.[2023]

In a study of 108 endometrial cancer patients who underwent robot-assisted laparoscopic surgery with sentinel lymph node (SLN) mapping, the 5-year recurrence-free survival rate was an impressive 95.4%, indicating strong long-term outcomes for this approach.

The study also reported a low rate of treatment complications, with the most common being peripheral neuropathy (9.3%), suggesting that SLN mapping is a safe alternative to traditional lymphadenectomy in managing endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"Long-term outcome in endometrial cancer patients after robot-assisted laparoscopic surgery with sentinel lymph node mapping". Jebens Nordskar, N., Hagen, B., V Vesterfjell, E., et al.[2022]

In a study of 90 patients with early-stage endometrial cancer, those who underwent sentinel lymph node biopsy (SLNB) reported significantly better quality of life (QoL) outcomes compared to those who had more invasive lymphadenectomy (LND), particularly in physical status and symptom management.

The SLNB group experienced less impact on sleep quality, pain, and dyspnoea, and also reported better sexual quality of life, indicating that SLNB is a beneficial surgical approach that enhances overall patient well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sentinel Lymph Node Impact on the Quality of Life of Patients with Endometrial Cancer. García-Pineda, V., Hernández, A., Garrido-Mallach, S., et al.[2023]

In a study of 69 patients with early-stage endometrial cancer, the sentinel node (SLN) mapping algorithm demonstrated a 100% sensitivity in detecting node positivity, significantly outperforming SLN mapping alone, which had a sensitivity of only 77.8%.

The SLN mapping algorithm was particularly effective in identifying positive nodes in high-risk endometrial cancer subtypes, where SLN mapping alone had a high false-negative rate of 42.9%, highlighting the importance of following the algorithm for accurate staging and treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective evaluation of the sentinel node mapping algorithm in endometrial cancer and correlation of its performance against endometrial cancer risk subtypes. Rajanbabu, A., Agarwal, R.[2018]

In a prospective study involving 10 patients with endometrial cancer, sentinel lymph node biopsy (SLNB) was successfully performed, allowing for the identification of sentinel lymph nodes in 8 out of 10 patients, demonstrating the technique's feasibility.

The results showed that SLNB accurately reflected the pathological status of the patients, with only one case of tumor metastasis found in the sentinel lymph nodes, indicating that this method is practical and safe for staging endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sentinel node identification and intraoperative lymphatic mapping. First results of a pilot study in patients with endometrial cancer. Fersis, N., Gruber, I., Relakis, K., et al.[2020]

A study involving 108 patients and 126 gynecologists found that both groups generally preferred sentinel lymph node (SLN) mapping for low- and intermediate-risk endometrial cancer, with patients showing a mean preference score of 4.29.

Key factors influencing patient preferences included the potential for survival gain, travel time to the hospital, and the risk of complications from subsequent radiotherapy, highlighting the importance of these factors in patient counseling regarding SLN mapping.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients' and gynecologists' views on sentinel lymph node mapping in low- and intermediate-risk endometrial cancer: a Dutch vignette study. Aarts, JWM., Burg, LC., Kasius, JC., et al.[2021]

This study aims to determine if sentinel lymph node (SLN) biopsy without systematic lymphadenectomy negatively affects oncological outcomes in endometrial cancer, focusing on 3-year disease-free survival and overall survival over a 5-year period.

The trial will involve 178 participants and assess not only survival rates but also the impact on morbidity, lower limb lymphedema, and quality of life, with results expected by 2027.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sentinel lymph node mapping versus sentinel lymph node mapping with systematic lymphadenectomy in endometrial cancer: an open-label, non-inferiority, randomized trial (ALICE trial). Baiocchi, G., Andrade, CEMC., Ribeiro, R., et al.[2022]

In a study of 6,414 women with early-stage endometrial cancer, sentinel lymph node (SLN) biopsy was found to significantly increase the likelihood of detecting micrometastasis compared to traditional lymphadenectomy, particularly in T1a and T1b disease.

The results indicated a 90% higher chance of identifying micrometastasis in T1a cases and a 68% higher chance in T1b cases when using SLN biopsy, suggesting that this method may enhance the detection of cancer spread in early-stage endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between sentinel lymph node biopsy and micrometastasis in endometrial cancer. Matsuo, K., Klar, M., Khetan, VU., et al.[2022]

Sentinel lymph node (SLN) mapping shows high detection rates and diagnostic accuracy in high-grade endometrial cancer, similar to its effectiveness in low-grade cases, based on current literature.

Current studies indicate that SLN mapping does not lead to inferior survival outcomes compared to traditional lymphadenectomy, although more prospective studies are needed to assess long-term results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lymphatic Mapping and Sentinel Node Biopsy in High-Grade Uterine Cancers. How, JA., Frumovitz, M., Stewart, KI., et al.[2023]

The ENDO-3 trial is a phase III randomized non-inferiority study involving 760 women with stage 1 endometrial cancer, comparing the outcomes of sentinel node biopsy versus no retroperitoneal node dissection, focusing on surgical recovery and disease-free survival.

The primary goal is to determine if sentinel node biopsy does not negatively impact recovery or increase morbidity compared to no-node dissection, with results expected by December 2024.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Obermair, A., Nicklin, J., Gebski, V., et al.[2022]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Comparison of oncological outcomes between sentinel lymph node biopsy and complete lymphadenectomy for endometrial cancer. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Robotic blue-dye sentinel lymph node detection for endometrial cancer - Factors predicting successful mapping. [2015]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Avoiding Full Lymphadenectomies in Intermediate- and High-Risk Endometrial Cancer by Sentinel Lymph Node Biopsy Implementation. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Accuracy and Survival Outcomes after National Implementation of Sentinel Lymph Node Biopsy in Early Stage Endometrial Cancer. [2023]

5. Ireland pubmed.ncbi.nlm.nih.gov

"Long-term outcome in endometrial cancer patients after robot-assisted laparoscopic surgery with sentinel lymph node mapping". [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Sentinel Lymph Node Impact on the Quality of Life of Patients with Endometrial Cancer. [2023]

7. Ireland pubmed.ncbi.nlm.nih.gov

A prospective evaluation of the sentinel node mapping algorithm in endometrial cancer and correlation of its performance against endometrial cancer risk subtypes. [2018]

8. Singapore pubmed.ncbi.nlm.nih.gov

Sentinel node identification and intraoperative lymphatic mapping. First results of a pilot study in patients with endometrial cancer. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Patients' and gynecologists' views on sentinel lymph node mapping in low- and intermediate-risk endometrial cancer: a Dutch vignette study. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Sentinel lymph node mapping versus sentinel lymph node mapping with systematic lymphadenectomy in endometrial cancer: an open-label, non-inferiority, randomized trial (ALICE trial). [2022]

11. Ireland pubmed.ncbi.nlm.nih.gov

Association between sentinel lymph node biopsy and micrometastasis in endometrial cancer. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Lymphatic Mapping and Sentinel Node Biopsy in High-Grade Uterine Cancers. [2023]

13. England pubmed.ncbi.nlm.nih.gov

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. [2022]