Sentinel Lymph Node Mapping for Endometrial Cancer

Recruiting at 44 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: NRG Oncology

Must not be taking: Chemotherapy, Immunotherapy

Disqualifiers: Morbid obesity, Prior surgery, Lymphedema, others

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

Compensation: Varies

Number of Visits: 4

Duration: At time of surgery

428 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new methods to detect the spread of endometrial cancer and reduce the risk of leg swelling after surgery. It compares two approaches during a hysterectomy: the traditional removal of lymph nodes (Pelvic Lymphadenectomy) and a newer method called Sentinel Lymph Node Mapping. This newer method uses a special dye, Indocyanine Green Solution, to identify cancer spread, potentially avoiding unnecessary lymph node removal. Women with stage I endometrial cancer planning a hysterectomy, who have not undergone prior radiation or chemotherapy, might be suitable candidates. The goal is to determine if the dye method can better predict and reduce the chance of leg swelling after surgery. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, progestin-containing therapies like megestrol, medroxyprogesterone, or levonorgestrel-containing IUDs are allowed.

What prior data suggests that sentinel lymph node mapping is safe for endometrial cancer patients?

Research shows that sentinel lymph node mapping is a safe and well-tolerated procedure for patients with endometrial cancer. Studies have found no serious allergic reactions or other immediate or delayed side effects when using indocyanine green (ICG) dye for this mapping. Doctors inject this dye to highlight sentinel lymph nodes, helping determine if cancer has spread.

Sentinel lymph node mapping is becoming more common in treating endometrial cancer because it involves removing fewer lymph nodes than traditional methods. This can reduce the risk of lymphedema, which is swelling in the legs due to fluid buildup.

While pelvic lymphadenectomy is a standard procedure, it can increase the risk of surgery-related and long-term lymphatic issues. Sentinel lymph node mapping aims to lower these risks by removing fewer lymph nodes.

Overall, the safety data for sentinel lymph node mapping, especially with ICG, appears promising, making it a potentially safer option compared to more extensive lymph node removal procedures. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about sentinel lymph node mapping for endometrial cancer because it offers a more targeted approach to identifying cancer spread. Unlike traditional methods that often involve removing numerous lymph nodes, this technique uses a special dye to highlight sentinel lymph nodes, which are the first nodes to which cancer cells are likely to spread. This can potentially reduce complications and side effects associated with more extensive lymph node removal. Additionally, in cases where mapping is successful, it minimizes unnecessary surgeries, making the treatment less invasive and more focused.

What evidence suggests that sentinel lymph node mapping is effective for reducing lymphedema in stage I endometrial cancer?

This trial will compare two approaches using sentinel lymph node mapping for endometrial cancer. In Arm 1, participants will receive a special dye called indocyanine green (ICG) and undergo sentinel lymph node mapping during minimally invasive surgery. This process helps doctors find cancer in the lymph nodes without removing many of them, reducing the risk of complications like leg swelling. In Arm 2, participants will also receive ICG and undergo sentinel lymph node mapping, but additional lymph nodes will be removed per standard care. Research has shown that using ICG accurately checks if endometrial cancer has spread to the lymph nodes, improving cancer staging accuracy while causing less harm to the patient. This method is considered reliable and less invasive, leading to better outcomes for patients. ^{3 6 7 8 9}

Who Is on the Research Team?

Edward J Tanner

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for adults with stage I endometrial cancer who are planning a hysterectomy and lymphatic assessment. They must be in good general health, not have chronic leg swelling or recent infections, radiation, or surgery that could affect the legs or pelvis. Prior cancers are okay if they don't impact this study's safety.

Inclusion Criteria

I have a confirmed diagnosis of endometrial cancer and will have surgery including lymph node assessment.

Exclusion Criteria

Patients whom the surgeon believes is not a candidate for pelvic lymphadenectomy due to medical comorbidities or other technical challenges (i.e. morbid obesity or prior surgery), History of chemotherapy or immunotherapy for the treatment of endometrial cancer. Progestin-containing therapies such as megestrol, medroxyprogesterone, or levonorgestrel-containing intrauterine device (IUD) are acceptable, History of radiation to the pelvis, groin or lower extremities, or surgery to the pelvic lymph nodes or inguinal lymph nodes, Patients who are going to undergo another elective surgery during the same operative event as their hysterectomy (i.e., sacrocolpopexy, cholecystectomy), Patients with severe, active co-morbidity defined as follows: History of patient or provider identified lower extremity lymphedema, History of patient or provider identified chronic lower extremity swelling, History of lower extremity or pelvic deep venous thromboembolism within 90 days of registration, History of lower extremity cellulitis within 90 days of registration, For the bioimpedance sub study only: patients with implantable metal devices (i.e. defibrillator, metal joint replacements, etc.) will not be eligible to participate in the bioimpedance sub study but will be eligible to participate in the overall study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive ICG dye via injection and undergo sentinel lymph node mapping and excision during standard minimally invasive hysterectomy. Additional lymph nodes may be removed depending on the arm.

At time of surgery

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments of lower extremity limb dysfunction and other outcomes.

24 months

Every 3 months for 1 year, then at 18 and 24 months

Long-term follow-up

Participants are monitored for progression-free and overall survival.

Up to 39 months

What Are the Treatments Tested in This Trial?

Interventions

• Indocyanine Green Solution
• Minimally Invasive Surgery
• Pelvic Lymphadenectomy
• Sentinel Lymph Node Mapping

Trial Overview The trial compares sentinel lymph node mapping (using dye and camera to find cancer spread) to standard lymph node dissection during hysterectomy in reducing leg swelling risk. It aims to determine which method better predicts long-term limb dysfunction.

How Is the Trial Designed?

Group I: Arm 2 (sentinel lymph node mapping, pelvic lymphadenectomy) Experimental Treatment 8 Interventions

Patients receive ICG dye via injection and undergo sentinel lymph node mapping and excision during standard minimally invasive hysterectomy. Additional lymph nodes around the uterus are removed per standard of care. Patients also undergo imaging as clinically indicated and optional blood sample collection throughout the study.

Group II: Arm 1 (sentinel lymph node mapping) Experimental Treatment 8 Interventions

Patients receive ICG dye via injection and undergo sentinel lymph node mapping and excision during standard minimally invasive hysterectomy. Lymph nodes around the uterus may be removed if the mapping and excision cannot be completed. Successful mapping requires no additional removal of lymph nodes. Patients also undergo imaging as clinically indicated and optional blood sample collection throughout the study.

Minimally Invasive Surgery is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Minimally Invasive Surgery for:

• General surgical procedures
• Gynecological surgeries
• Endometrial cancer staging

Approved in United States as Minimally Invasive Surgery for:

• General surgical procedures
• Gynecological surgeries
• Endometrial cancer staging

Approved in Canada as Minimally Invasive Surgery for:

• General surgical procedures
• Gynecological surgeries
• Endometrial cancer staging

Who Is Running the Clinical Trial?

NRG Oncology

Lead Sponsor

Trials

242

Recruited

105,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 1576 endometrial cancer patients, sentinel lymph node (SLN) mapping showed a high detection rate of 93.4%, with most SLNs located at the external iliac and obturator levels, indicating these areas are critical for assessing metastasis.

Factors such as older age, higher body mass index, and non-endometrioid cancer histology were associated with lower mapping success, suggesting that these characteristics may hinder effective SLN identification in surgical planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anatomical distribution of sentinel lymph nodes in patients with endometrial cancer: a multicenter study. Restaino, S., Buda, A., Puppo, A., 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]

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]

Sentinel lymph node (SLN) mapping is highly successful in detecting metastases in endometrial cancer, with 74.2% of the 819 patients achieving successful bilateral mapping during minimally-invasive staging.

Higher body mass index (BMI) and certain histological types of cancer are significant risk factors for failed SLN mapping, indicating that patients with a BMI over 30 and those with macrometastases or micrometastases may face challenges in accurate detection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical factors associated with failed sentinel lymph node mapping in endometrial cancer. Garrett, AA., Wield, A., Mumford, B., et al.[2022]

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 110 patients with endometrial cancer, the bilateral sentinel lymph node (SLN) mapping using indocyanine green (ICG) had a detection rate of 72.7%, indicating a moderate success rate for this staging method.

The only significant factor influencing the success of bilateral SLN mapping was the surgeon performing the procedure, suggesting that surgical expertise plays a crucial role in the effectiveness of this technique.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sentinel Lymph Node Biopsy in the Treatment of Endometrial Cancer: Why We Fail? Results of a Prospective Multicenter Study on the Factors Associated with Failure of Node Mapping with Indocyanine Green. Ianieri, MM., Puppo, A., Novelli, A., et al.[2019]

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 472 patients with endometrial cancer, sentinel lymph node (SLN) mapping did not show a significant difference in overall recurrence-free survival compared to systematic lymphadenectomy, suggesting similar long-term outcomes.

However, SLN mapping significantly reduced the risk of pelvic sidewall recurrences, with only 30% of recurrences occurring in this area compared to 71.4% in the systematic lymphadenectomy group, indicating a potential advantage in targeting high-risk lymph nodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of sentinel lymph node mapping on recurrence patterns in endometrial cancer. How, J., Gauthier, C., Abitbol, J., et al.[2018]

In a study of 780 patients with early-stage endometrial cancer, sentinel lymph node (SLN) mapping combined with staging lymphadenectomy significantly increased the detection of lymph node metastasis compared to staging lymphadenectomy alone, with a detection rate of 30.3% in the mapped group versus 14.7% in the non-mapped group.

The use of SLN mapping also led to a higher rate of adjuvant therapies, including chemotherapy and radiation, with 28.6% of the mapped group receiving these treatments compared to 16.3% in the non-mapped group, indicating its potential to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sentinel lymph node mapping with staging lymphadenectomy for patients with endometrial cancer increases the detection of metastasis. Holloway, RW., Gupta, S., Stavitzski, NM., et al.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6475506/

Sentinel lymph node mapping using indocyanine green in ... SLN mapping technique using NIR fluorescence imaging with ICG appears to be accurate method in most of the patients with cervical or endometrial carcinoma.

2. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X24159439

EV116/#458 Effectiveness of indocyanine green ... This retrospective study analyzed 13 endometrial cancer patients who underwent SLN mapping with ICG fluorescence imaging at an oncology center in Salvador, ...

3. bmcsurg.biomedcentral.com bmcsurg.biomedcentral.com/articles/10.1186/s12893-025-03232-w

Comparison of identification of sentinel lymph nodes between ... This study aimed to assess the comparative effectiveness of indocyanine green and methylene blue in the marking and identification of ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02131558

Study Details | NCT02131558 | Indocyanine Green and ... The primary outcome is to determine whether sentinel lymph nodes (SLN) were accurately visualized using Indocyanine green (ICG) and near-infrared (NIR) imaging.

5. international-journal-of-gynecological-cancer.com international-journal-of-gynecological-cancer.com/article/S1048-891X(24)21255-X/fulltext

Sentinel Lymph Node Mapping With Indocyanine Green In ... Sentinel lymph node mapping using ICG offers a highly accurate method for detecting lymph node metastases in patients with endometrial cancer.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4889617/

Impact of Indocyanine Green for Sentinel Lymph Node ... ICG was significantly superior to 99m Tc with blue dye in terms of bilateral OM in women with early stage endometrial and cervical cancer.

7. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X24013136

Let go of the myth: safety of indocyanine green for sentinel ... Conclusion. Indocyanine green injection for sentinel lymph node mapping in patients with endometrial cancer caused no immediate/delayed anaphylactic or other ...

8. ejgo.org ejgo.org/pdf/10.3802/jgo.2022.33.e73

Randomized comparison between sentinel lymph node ... In a recent large-scale prospective endometrial cancer study, SLN mapping using indocyanine green (ICG) and fluorescent imaging was successful.

9. asco.org asco.org/abstracts-presentations/ABSTRACT134759

Fluorescence-guided lymph node mapping with ... Data was collected for the number of nodes identified, the location of SLN's, the duration of procedure and the pathology characteristics of the SLN's compared ...