Clinical trial NCT05646316: Impact of Sentinel Lymph Node Mapping on Patient Reported Lower Extremity Limb Dysfunction in Stage I Endometrial Cancer
Official title: A Phase III Trial Of The Impact Of Sentinel Lymph Node Mapping On Patient Reported Lower Extremity Limb Dysfunction In Endometrial Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Stage I Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8
Lead sponsor: NRG Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2022-12-12
Enrollment: 428
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief 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.

Detailed 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 and excision 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 and excision 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 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.

ARM 2: 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 in both arms also undergo imaging as clinically indicated and optional blood sample collection throughout the study.

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

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of patient-reported lower extremity limb dysfunction
timeFrame: From 18 months post-hysterectomy after undergoing lymphatic assessment to 39 months
Secondary outcomes:
measure: The incidence of lymphedema by quantifiable lower extremity limb changes
timeFrame: From enrollment and at 3, 6, 9, 12, and 18 months after surgery
measure: The incidence of lymphedema by bioimpedance assessments (if available)
timeFrame: From enrollment and at 3, 6, 9, 12, and 18 months after surgery.
measure: Rate of successful bilateral SLN identification
timeFrame: At time of surgery
measure: Rate of successful identification of lymph node metastasis
timeFrame: At time of surgery
measure: Rate of perioperative complications
timeFrame: At time of surgery
Other outcomes:
measure: Adjuvant therapy decisions
timeFrame: Up to 24 months
measure: incremental cost-effectiveness ratio (ICER) of a SLN mapping algorithm
timeFrame: From enrollment and at 3, 6, 9, 12, and 18 months after surgery
measure: Progression free survival
timeFrame: 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
measure: Overall survival
timeFrame: Duration of time from study entry to time of death or the date of last contact, assessed at 2 years after enrollment
Locations:
city: Washington
country: United States
facility: George Washington University Medical Center
state: District of Columbia
city: Coral Gables
country: United States
facility: UM Sylvester Comprehensive Cancer Center at Coral Gables
state: Florida
city: Deerfield Beach
country: United States
facility: UM Sylvester Comprehensive Cancer Center at Deerfield Beach
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine-Sylvester Cancer Center
state: Florida
city: Miami
country: United States
facility: UM Sylvester Comprehensive Cancer Center at Kendall
state: Florida
city: Plantation
country: United States
facility: UM Sylvester Comprehensive Cancer Center at Plantation
state: Florida
city: Augusta
country: United States
facility: Augusta University Medical Center
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Warrenville
country: United States
facility: Northwestern Medicine Cancer Center Warrenville
state: Illinois
city: Carmel
country: United States
facility: IU Health North Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University/Melvin and Bren Simon Cancer Center
state: Indiana
city: Marrero
country: United States
facility: West Jefferson Medical Center
state: Louisiana
city: Metairie
country: United States
facility: East Jefferson General Hospital
state: Louisiana
city: New Orleans
country: United States
facility: Louisiana State University Health Science Center
state: Louisiana
city: New Orleans
country: United States
facility: University Medical Center New Orleans
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland/Greenebaum Cancer Center
state: Maryland
city: Bel Air
country: United States
facility: UM Upper Chesapeake Medical Center
state: Maryland
city: Detroit
country: United States
facility: Wayne State University/Karmanos Cancer Institute
state: Michigan
city: Farmington Hills
country: United States
facility: Weisberg Cancer Treatment Center
state: Michigan
city: Flint
country: United States
facility: McLaren Cancer Institute-Flint
state: Michigan
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Maple Grove
country: United States
facility: Fairview Clinics and Surgery Center Maple Grove
state: Minnesota
city: Maplewood
country: United States
facility: Saint John's Hospital - Healtheast
state: Minnesota
city: Princeton
country: United States
facility: Fairview Northland Medical Center
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Wyoming
country: United States
facility: Fairview Lakes Medical Center
state: Minnesota
city: Springfield
country: United States
facility: Mercy Hospital Springfield
state: Missouri
city: Billings
country: United States
facility: Saint Vincent Healthcare
state: Montana
city: Billings
country: United States
facility: Saint Vincent Frontier Cancer Center
state: Montana
city: Billings
country: United States
facility: Intermountain Health West End Clinic
state: Montana
city: Butte
country: United States
facility: Saint James Community Hospital and Cancer Treatment Center
state: Montana
city: Kearney
country: United States
facility: Fred and Pamela Buffett Cancer Center - Kearney
state: Nebraska
city: Omaha
country: United States
facility: Nebraska Medicine-Village Pointe
state: Nebraska
city: Omaha
country: United States
facility: Alegent Health Bergan Mercy Medical Center
state: Nebraska
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: Women's Cancer Center of Nevada
state: Nevada
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Bryn Mawr
country: United States
facility: Bryn Mawr Hospital
state: Pennsylvania
city: Paoli
country: United States
facility: Paoli Memorial Hospital
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: Women and Infants Hospital
state: Rhode Island
city: Dallas
country: United States
facility: Parkland Memorial Hospital
state: Texas
city: Dallas
country: United States
facility: UT Southwestern/Simmons Cancer Center-Dallas
state: Texas
city: Fort Worth
country: United States
facility: UT Southwestern/Simmons Cancer Center-Fort Worth
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Texas Medical Center
state: Texas
city: Houston
country: United States
facility: Methodist Willowbrook Hospital
state: Texas
city: Houston
country: United States
facility: Houston Methodist West Hospital
state: Texas
city: Richardson
country: United States
facility: UT Southwestern Clinical Center at Richardson/Plano
state: Texas
city: Sugar Land
country: United States
facility: Houston Methodist Sugar Land Hospital
state: Texas
city: The Woodlands
country: United States
facility: Houston Methodist The Woodlands Hospital
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
Study officials:
affiliation: NRG Oncology
name: Edward J Tanner
role: PRINCIPAL_INVESTIGATOR
References: