Sentinel Node Mapping in High Risk Endometrial Cancer (ALICE)

February 16, 2022 updated by: Glauco Baiocchi Neto, AC Camargo Cancer Center

Sentinel Node Mapping Versus Sentinel Node Mapping With Systematic Lymphadenectomy in High Risk Endometrial Cancer: a Open Label, Non-inferiority, Randomized Trial.

This study will evaluate the role of systematic lymphadenectomy after sentinel node (SLN) mapping in high risk endometrial cancer (high grade histologies or deep myometrial invasion). The participants will be randomized in a non-inferiority controlled trial in 2 groups: SLN mapping or SLN mapping followed by systematic lymphadenectomy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Although most patients with endometrial cancer present with early-stage disease, the standard treatment still includes systematic lymph node dissection for staging. Recently, SLN mapping has emerged as an acceptable surgical strategy when deciding between complete lymphadenectomy and no node dissection. This approach can help avoid the morbidity that is associated with a complete lymphadenectomy, such as neurovascular injury, lymphocyst formation, and lymphedema. A recent meta-analysis that included 55 studies and 4915 patients reported an overall SLN detection rate of 81% versus 50% for bilateral SLNs. Moreover, the use of indocyanine green increased the bilateral SLN detection rate compared with blue dye (74.6% vs. 50.5%). Yet, the studies noted an overall sensitivity of 96% and false negative rates of less than 5% when analyzed per hemipelvis. Since 2014, the National Comprehensive Cancer Network (NCCN) guidelines have recommended SLN mapping as an alternative option for node staging in endometrial cancer. However, most studies on SLN mapping have included patients who are at low risk for lymph node involvement and thus might underestimate the false negative rate. Recently, Soliman et al. reported a series of only high-grade and deep invasive endometrial cancers for which patients underwent SLN mapping, followed by pelvic and para-aortic lymph node dissection. An 89% detection rate was reported, suggesting that SLN mapping accurately identifies node metastases, with an negative predictive value (NPV) of 98% and an false negative predictive value (FNPV) of 2% when analyzed by hemipelvises. Positive nodes were found in 22.8% of patients (43% of isolated tumor cells and micrometastases), and in 40% of cases, the SLN was the only positive node. Data from the investigators corroborate these findings-26.7% of high-risk cases had positive nodes (50% of isolated tumor cells and micrometastases), and when analyzed by hemipelvis, the NPV was 97.9% and the FNPV was 2.1%. In 14 (70%) patients, the SLN was the only positive node. Moreover, there are few publications that have compared the results of the addition of SLN mapping to lymphadenectomy alone. Raimond et al. compared 156 patients that had SLN mapping with 95 who had pelvic node dissection. In their study, SLN mapping and imuno-histochemistry (IHC) were performed in low- and intermediate-risk patients, and the former detected metastatic node 3 times more often than complete pelvic lymphadenectomy alone (16.2% vs. 5.1%, p=0.03). They had no false negatives, and the IHC findings modified the adjuvant therapy in half of all cases. Holloway et al. compared a series of 661 patients who had undergone pelvic and para-aortic lymphadenectomy with 119 who were subjected to SLN mapping plus node dissection, including 68 high-intermediate- and high-risk patients in the SLN mapping group (GOG99 stratification). Despite the similarity in demographics and pathological risk factors, the SLN group had more LN metastases that were detected (30.3% vs. 16.3%; p<0.001) and received more adjuvant therapy (28.6% vs. 16.3%; p=0.003). The SLN was the only positive node in 18 (50%) of mapped cases, and the false negative rate was 2.8%.The investigators recently published a series on high risk endometrial cancer and also recorded a higher pelvic node metastasis rate for the SLN mapping group (26.7% vs. 14.3%, p=0.02) but no significant difference in para-aortic node metastases (13.5% vs. 5.6%, p=0.12). Notably, if considered only patients in whom SLNs were mapped, 31.3% had pelvic positive nodes. Despite the differences in uterine risk factors between groups, 10.6% (8/75) of patients in the SLN group had node metastasis that was diagnosed only after IHC. Excluding these patients, the SLN group would have had a node positivity rate of 17.3%, similar to the N-SLN group (17.4%), reinforcing the impact of IHC in the detection of node metastases. Moreover, the SLN group received more adjuvant chemotherapy (33.5% vs. 48%). The overall detection rate for SLNs was 85.3%, and bilateral SLNs were observed in 60%. The investigators noted an overall sensitivity of 90%, a negative predictive value of 95.7%, and a false negative predictive value of 4.3%. Recently, Touhami et al. showed that the risk of non-SLN metastasis is 61% when the SLN metastasis size is ≥2mm, and 5% for SLN metastasis of <2mm. However, one of the remaining uncertainties is the role of systematic lymphadenectomy after a positive SLN. In other words, is there any benefit in favor of systematic lymphadenectomy in a patient that already undergo adjuvant chemotherapy? The investigators hypothesized that there is no disease free survival benefit in adding systematic lymphadenectomy to only sentinel node mapping and proposed a prospective randomized controlled non-inferiority trial comparing SLN mapping to SLN mapping with systematic lymphadenectomy in high risk endometrial cancer.

Study Type

Interventional

Enrollment (Anticipated)

178

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Brazil
    • Parana
    • SP
      • Sao Paulo, SP, Brazil, 01509010
      • São Paulo, SP, Brazil
      • São Paulo, SP, Brazil
    • Sao Paulo
      • Barretos, Sao Paulo, Brazil

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • High grade histologies (endometrioid grade 3, serous, clear cell and carcinosarcoma)
  • Endometrioid grades 1 or 2 with myometrial invasion of ≥50%
  • Endometrioid grades 1 or 2 with cervical invasion
  • Clinically suitable to receive systematic lymphadenectomy
  • Consent statement

Exclusion Criteria:

  • Previous hysterectomy in other institution
  • Presence of extra-uterine disease (peritoneal, visceral or suspicious lymph node metastasis)
  • Previous pelvic node dissection

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Sentinel Node Mapping plus Lymphadenectomy
Patients with high risk endometrial cancer will undergo Sentinel Node Mapping followed by Systematic Pelvic and Para-Aortic Lymphadenectomy
Procedure: Sentinel Node Mapping
At least one sentinel node should be retrieved in both hemipelvis. If no sentinel node is found in one hemipelvis, a side specific lymphadenectomy will be performed.
Procedure: Lymphadenectomy
Systematic Pelvic and Para-Aortic Lymphadenectomy
Experimental: Sentinel Node Mapping
Patients with high risk endometrial cancer will undergo Sentinel Node Mapping per NCCN algorithm
Procedure: Sentinel Node Mapping
At least one sentinel node should be retrieved in both hemipelvis. If no sentinel node is found in one hemipelvis, a side specific lymphadenectomy will be performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recurrence
Time Frame: 3 years
Recurrence Free Survival
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Survival
Time Frame: 5 years
Overall Survival
5 years
Early morbidity
Time Frame: <30 days after surgery
Surgical and clinical morbidity
<30 days after surgery
Late morbidity
Time Frame: >30 days after surgery
Surgical and clinical morbidity
>30 days after surgery
Lymphedema
Time Frame: Evaluation before surgery and after 6 and 12 months of follow-up
Presence and lymphedema graduation
Evaluation before surgery and after 6 and 12 months of follow-up
Quality of Life Questionary (QLQ)
Time Frame: Evaluation before surgery and after 1 and 6 months of follow-up
EORTC QLQ-C30
Evaluation before surgery and after 1 and 6 months of follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AC Camargo Cancer Center

Investigators

  • Principal Investigator: Glauco Baiocchi, MD, PhD, Department of Gynecologic Oncology - AC Camargo Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 22, 2017

Primary Completion (Anticipated)

December 20, 2024

Study Completion (Anticipated)

December 20, 2024

Study Registration Dates

First Submitted

December 4, 2017

First Submitted That Met QC Criteria

December 4, 2017

First Posted (Actual)

December 8, 2017

Study Record Updates

Last Update Posted (Actual)

February 18, 2022

Last Update Submitted That Met QC Criteria

February 16, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2.392.088

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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