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Sentinel Node Mapping in High Risk Endometrial Cancer (ALICE)

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ClinicalTrials.gov Identifier: NCT03366051
Recruitment Status : Recruiting
First Posted : December 8, 2017
Last Update Posted : August 13, 2019
Sponsor:
Information provided by (Responsible Party):
Glauco Baiocchi Neto, AC Camargo Cancer Center

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
Endometrial Cancer Lymph Node Metastases Procedure: Sentinel Node Mapping Procedure: Lymphadenectomy Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 162 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized 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 : December 22, 2017
Estimated Primary Completion Date : December 20, 2021
Estimated Study Completion Date : December 20, 2024

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.




Primary Outcome Measures :
  1. Recurrence [ Time Frame: 3 years ]
    Recurrence Free Survival


Secondary Outcome Measures :
  1. Survival [ Time Frame: 5 years ]
    Overall Survival

  2. Early morbidity [ Time Frame: <30 days after surgery ]
    Surgical and clinical morbidity

  3. Late morbidity [ Time Frame: >30 days after surgery ]
    Surgical and clinical morbidity

  4. Lymphedema [ Time Frame: Evaluation before surgery and after 6 and 12 months of follow-up ]
    Presence and lymphedema graduation

  5. Quality of Life Questionary (QLQ) [ Time Frame: Evaluation before surgery and after 1 and 6 months of follow-up ]
    EORTC QLQ-C30



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03366051


Contacts
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Contact: Bruna Goncalves, RN, MSc 551121895110 bruna.goncalves@accamargo.org.br

Locations
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Brazil
Hospital Erasto Gaertner Not yet recruiting
Curitiba, Parana, Brazil
Contact: Reitan Ribeiro, MD       reitanribeiro@hotmail.com   
Hospital do Cancer de Barretos Recruiting
Barretos, Sao Paulo, Brazil
Contact: Carlos Andrade, MD, PhD       mdcarlosandrade@gmail.com   
AC Camargo Cancer Center Recruiting
Sao Paulo, SP, Brazil, 01509010
Contact: Glauco Baiocchi, MD, PhD    551121895110    glauco.baiocchi@accamargo.org.br   
Sponsors and Collaborators
AC Camargo Cancer Center
Investigators
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Principal Investigator: Glauco Baiocchi, MD, PhD Department of Gynecologic Oncology - AC Camargo Cancer Center

Publications:

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Responsible Party: Glauco Baiocchi Neto, Director, Department of Gynecologic Oncology, AC Camargo Cancer Center
ClinicalTrials.gov Identifier: NCT03366051     History of Changes
Other Study ID Numbers: 2.392.088
First Posted: December 8, 2017    Key Record Dates
Last Update Posted: August 13, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Glauco Baiocchi Neto, AC Camargo Cancer Center:
Endometrial Cancer
Sentinel Lymph Node
Lymphadenectomy
Additional relevant MeSH terms:
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Endometrial Neoplasms
Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Genital Diseases, Female