Impact of Sentinel Lymph Node Mapping on Patient Reported Lower Extremity Limb Dysfunction in Stage I Endometrial Cancer

Stage I Uterine Corpus Cancer AJCC v8 Clinical Trial

Official title:

A Phase III Trial of the Impact of Sentinel Lymph Node Mapping on Patient Reported Lower Extremity Limb Dysfunction in Endometrial Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05646316
• Other study ID #: NRG-CC010
• Secondary ID: NCI-2022-05090NR
• Status: Recruiting
• Phase: Phase 3
• Start date: December 7, 2022
• Est. completion date: October 31, 2026

Study information

• Verified date: May 2024
• Source: NRG Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase III trial compares the effect of sentinel lymph node mapping to standard lymph node dissection in reducing the risk of swelling in the legs (lymphedema) in patients undergoing a hysterectomy for stage I endometrial cancer. Standard lymph node dissection removes lymph nodes around the uterus during a hysterectomy to look for spread of cancer from the uterus to nearby lymph nodes. Sentinel lymph node mapping uses a special dye and camera to look for cancer that may have spread to nearby lymph nodes. Comparing the results of the procedures may help doctors predict the risk of long-term swelling in the legs.

Description:

PRIMARY OBJECTIVES:

I. To compare the rates of lower extremity limb dysfunction (defined as a >= 4-point increase in Gynecologic Cancer Lymphedema Questionnaire [GCLQ] symptom score from baseline) in patients with apparent uterine confined endometrial cancer randomized to one of two lymphatic assessment strategies at time of hysterectomy:

Ia. Sentinel lymph node mapping followed by side-specific lymphadenectomy on sides without a sentinel lymph node (SLN) identified according to a National Comprehensive Cancer Network (NCCN) guidelines approved algorithm (Arm 1); Ib. Sentinel lymph node mapping according to an NCCN Guidelines approved algorithm followed by bilateral pelvic +/- para-aortic lymphadenectomy (Arm 2).

SECONDARY OBJECTIVE:

I. To compare changes in lower extremity limb circumference in patients with apparent uterine confined endometrial cancer randomized to one of two lymphatic assessment strategies at time of hysterectomy.

II. To validate the test characteristics of a SLN mapping algorithm including SLN detection rates, rate of perioperative complications, rate of identifying lymphatic metastases, and detection of micrometastases using pathologic ultra-staging.

EXPLORATORY OBJECTIVES:

I. To compare adjuvant therapy decisions in patients with apparent uterine confined endometrial cancer randomized to one of two lymphatic assessment strategies at time of hysterectomy.

II. To explore the impact of patient characteristics (age, body mass index [BMI], race), extent of lymph node dissection, and adjuvant therapy decisions (radiation, chemotherapy) on the development of lower extremity limb dysfunction - as well as their interaction with lymph node assessment strategies.

III. To evaluate the cost-effectiveness of SLN mapping with or without completion of lymphadenectomy for endometrial cancer.

SAFETY OBJECTIVE:

I. To compare progression free and overall survival in patients with apparent uterine confined endometrial cancer randomized to one of two lymphatic assessment strategies at time of hysterectomy.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM 1: Patients receive ICG dye via injection and undergo sentinel lymph node mapping during standard minimally invasive hysterectomy. Lymph nodes around the uterus may be removed if the mapping cannot be completed. Successful mapping requires no additional removal of lymph nodes.

ARM 2: Patients receive ICG dye via injection and undergo sentinel lymph node mapping during standard minimally invasive hysterectomy. Additional lymph nodes around the uterus are removed per standard of care.

Patients in both arms also undergo imaging as clinically indicated.

After completion of study intervention, patients are followed every 3 months for one year and at 18 and 24 months.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 428
• Est. completion date: October 31, 2026
• Est. primary completion date: October 31, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically proven diagnosis of endometrial cancer based on endometrial sampling with a plan to undergo laparoscopic or robotic hysterectomy and lymphatic assessment as part of primary management. Biopsy must be performed within 90 days prior to registration

• Clinical stage I endometrial cancer based on the following diagnostic workup:

• History/physical examination within 30 days prior to registration is reassuring for the absence of metastatic disease

• Age >= 18 years

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2

• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information

• Patients must speak English or Spanish

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

Related Conditions & MeSH terms

• Endometrial Neoplasms
• Stage I Uterine Corpus Cancer AJCC v8

Intervention

Procedure:
• Diagnostic Imaging
Undergo imaging

Drug:
• Indocyanine Green Solution
Given via injection

Procedure:
• Minimally Invasive Surgery
Undergo minimally invasive hysterectomy
• Pelvic Lymphadenectomy
Undergo pelvic lymphadenectomy

Other:
• Questionnaire Administration
Ancillary studies

Procedure:
• Sentinel Lymph Node Mapping
Undergo sentinel lymph node mapping

Locations

Country	Name	City	State
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	IU Health North Hospital	Carmel	Indiana
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Northwestern University	Chicago	Illinois
United States	Parkland Memorial Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	McLaren Cancer Institute-Flint	Flint	Michigan
United States	Houston Methodist Hospital	Houston	Texas
United States	Houston Methodist West Hospital	Houston	Texas
United States	Methodist Willowbrook Hospital	Houston	Texas
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Women's Cancer Center of Nevada	Las Vegas	Nevada
United States	Fairview Clinics and Surgery Center Maple Grove	Maple Grove	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	West Jefferson Medical Center	Marrero	Louisiana
United States	East Jefferson General Hospital	Metairie	Louisiana
United States	Louisiana State University Health Science Center	New Orleans	Louisiana
United States	University Medical Center New Orleans	New Orleans	Louisiana
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Fairview Northland Medical Center	Princeton	Minnesota
United States	Women and Infants Hospital	Providence	Rhode Island
United States	UT Southwestern Clinical Center at Richardson/Plano	Richardson	Texas
United States	Regions Hospital	Saint Paul	Minnesota
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Houston Methodist Sugar Land Hospital	Sugar Land	Texas
United States	Houston Methodist The Woodlands Hospital	The Woodlands	Texas
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	George Washington University Medical Center	Washington	District of Columbia
United States	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	Fairview Lakes Medical Center	Wyoming	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
NRG Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adjuvant therapy decisions	Adjuvant therapy decisions will be compared for patients according to study arm allocation after accounting for tumor characteristics, stage, and patient demographics to determine whether lymph node mapping strategies was associated with a difference in adjuvant therapy choice.	Up to 24 months
Other	incremental cost-effectiveness ratio (ICER) of a SLN mapping algorithm	To determine the ICER of a SLN mapping algorithm with or without full lymphadenectomy for endometrial cancer using the European Quality of Life 5 Dimensions 3 Level Version, medical records (EQ-5D-5L), and questionnaire to gather resource utilization for lymphedema treatment. The visual analog scale and index scores from the EQ-5D-DL will be calculated at baseline and change scores corresponding at each collected follow-up time point then compared between treatment arms using a t-test with a 2-sided significance level of 0.05. At each time point, the EQ-5D-5L is obtained, and quality of life related utility scores will be calculated from the EQ-5D-5L. A mean utility score and confidence intervals will be used for cost-effective modeling. Quality-adjusted life years (QALYs) are calculated as the weighted sum of survival time and quality of life-based utilities. A Markov model will be used to model cost for this analysis.	From enrollment and at 3, 6, 9, 12, and 18 months after surgery
Other	Progression free survival	This endpoint is not expected to be sufficiently powered for a definitive comparison and will therefore be treated as supportive evidence.	The duration of time from study entry to time of progression or death, whichever occurs first, or date of last contact if neither progression nor death has occurred, assessed at 2 years after enrollment
Other	Overall survival	This endpoint is not expected to be sufficiently powered for a definitive comparison and will therefore be treated as supportive evidence.	Duration of time from study entry to time of death or the date of last contact, assessed at 2 years after enrollment
Primary	Incidence of patient-reported lower extremity limb dysfunction	The primary endpoint is the incidence of patient-reported lower extremity limb dysfunction at 18 months post-hysterectomy after undergoing lymphatic assessment according to a National Comprehensive Cancer Network (NCCN) guideline-based sentinel lymph node (SLN) mapping algorithm with or without completion of lymphadenectomy. The primary endpoint will be assessed using the Gynecologic Cancer Lymphedema Questionnaire (GCLQ) questionnaire. Surveys will be performed at enrollment (pre-surgery) and at 3, 6, 9, 12, and 18 months post-surgery. Patient-reported lower extremity limb dysfunction will be defined as an increase in GCLQ symptom score of at least four (4) points from baseline at any time during the 18 months follow-up. The primary null hypothesis will be evaluated with an intent-to-treat chi-squared test, adjusted for stratification factors. Proportional hazards modeling will be used to generate a hazard ratio and 95% confidence limits of Arm 1 versus Arm 2.	From 18 months post-hysterectomy after undergoing lymphatic assessment to 39 months
Secondary	The incidence of lymphedema by quantifiable lower extremity limb changes	Patients will undergo circumferential lower extremity limb measures at three locations along each leg. Change will be estimated as measurement at baseline subtracted from measurement at follow-up. This will be assessed in both legs separately.	From enrollment and at 3, 6, 9, 12, and 18 months after surgery
Secondary	The incidence of lymphedema by bioimpedance assessments (if available)	Patients will undergo circumferential lower extremity limb measures at three locations along each leg. Change will be estimated as measurement at baseline subtracted from measurement at follow-up. This will be assessed in both legs separately. The SOZO device by ImpediMed provides an L-Dex score for each leg at each assessment point as each limb is at risk for lower extremity lymphedema.	From enrollment and at 3, 6, 9, 12, and 18 months after surgery.
Secondary	Rate of successful bilateral SLN identification	Will be assessed in both, and only as the time of surgery.	At time of surgery
Secondary	Rate of successful identification of lymph node metastasis	Will be assessed in both, and only as the time of surgery. The rate of lymph node metastasis identification during surgery will be compared between groups, with either t-tests or chi-squared tests where appropriate.	At time of surgery
Secondary	Rate of perioperative complications	Will be assessed in both arms separately, and only as the time of surgery. The rate of perioperative complications during surgery will be compared between groups, with either t-tests or chi-squared tests where appropriate.	At time of surgery