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ALICE: Sentinel Node Mapping in High Risk Endometrial Cancer

Sponsor
AC Camargo Cancer Center (Other)
Overall Status
Recruiting
CT.gov ID
NCT03366051
Collaborator
(none)
178
Enrollment
5
Locations
2
Arms
83.9
Anticipated Duration (Months)
35.6
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Procedure: Sentinel Node Mapping
  • Procedure: Lymphadenectomy
 N/A

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 Design

Study Type:
Interventional
Anticipated Enrollment :
178 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Randomized Controlled Non-Inferiority TrialRandomized Controlled Non-Inferiority Trial
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Sentinel Node Mapping Versus Sentinel Node Mapping With Systematic Lymphadenectomy in High Risk Endometrial Cancer: a Open Label, Non-inferiority, Randomized Trial.
Actual Study Start Date :
Dec 22, 2017
Anticipated Primary Completion Date :
Dec 20, 2024
Anticipated Study Completion Date :
Dec 20, 2024

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

  1. Recurrence [3 years]

    Recurrence Free Survival

Secondary Outcome Measures

  1. Survival [5 years]

    Overall Survival

  2. Early morbidity [<30 days after surgery]

    Surgical and clinical morbidity

  3. Late morbidity [>30 days after surgery]

    Surgical and clinical morbidity

  4. Lymphedema [Evaluation before surgery and after 6 and 12 months of follow-up]

    Presence and lymphedema graduation

  5. Quality of Life Questionary (QLQ) [Evaluation before surgery and after 1 and 6 months of follow-up]

    EORTC QLQ-C30

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Hospital Erasto Gaertner Curitiba Parana Brazil
2 Hospital do Cancer de Barretos Barretos Sao Paulo Brazil
3 AC Camargo Cancer Center Sao Paulo SP Brazil 01509010
4 Albert Einstein Hospital São Paulo SP Brazil
5 Sao Camilo Oncologia São Paulo SP Brazil

Sponsors and Collaborators

  • AC Camargo Cancer Center

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Glauco Baiocchi Neto, Director, Department of Gynecologic Oncology, AC Camargo Cancer Center
ClinicalTrials.gov Identifier:
NCT03366051
Other Study ID Numbers:
  • 2.392.088
First Posted:
Dec 8, 2017
Last Update Posted:
Feb 18, 2022
Last Verified:
Feb 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Glauco Baiocchi Neto, Director, Department of Gynecologic Oncology, AC Camargo Cancer Center
Endometrial Cancer
Sentinel Lymph Node
Lymphadenectomy
Additional relevant MeSH terms:
Endometrial Neoplasms
Lymphatic Metastasis

Study Results

No Results Posted as of Feb 18, 2022