Uterine Manipulation During Minimally Invasive Surgery for Early Stage Endometrial Cancer

Study Overview
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Brief Summary
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This is a prospective, multi-center, randomized non-inferiority phase III study to evaluate if patients undergoing a minimally invasive surgery for early stage uterine cancer have cancer cells in the fluid that is obtained at the time of their surgery when a uterine manipulator is placed versus patients who do not have a uterine manipulator placed.

Detailed Description
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In most cases, patients who have early stage endometrial cancer undergo a surgery to remove the uterus, cervix, tubes, ovaries, and occasionally lymph nodes. This is usually done through a minimally invasive (not a large incision) surgery. To accomplish this, the uterus needs to be manipulated (moved around) to help the surgeon complete your surgery. This is usually done with a device called a uterine manipulator and the majority of surgeons use this device in any patient undergoing a minimally invasive hysterectomy (removal of the uterus and cervix). Even though the majority of surgeons use a manipulator, there are some surgeons who believe there is a possibility that cancer cells inside the uterus can be spilled into the abdomen through the fallopian tubes. This may cause a higher risk of spreading the cancer and or of the cancer coming back. Currently, there are very limited research studies directly looking at whether the uterine manipulator may cause these cells to appear in the abdomen. The purpose of this study is to see if patients undergoing a minimally invasive surgery for early stage uterine cancer have cancer cells in the fluid that is obtained at the time of their surgery when a uterine manipulator is placed versus patients who do not have a uterine manipulator placed. A computer program will randomly assign the subjects to one of two groups. One group will have minimally invasive surgery with the use of a uterine manipulator and the other group will have minimally invasive surgery without the use of a uterine manipulator. Researchers will use the information from this study to decide how best to take care of patients undergoing minimally invasive surgery for uterine cancer.

Official Title
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Uterine Manipulation During Minimally Invasive Surgery for Early Stage Endometrial Cancer

Conditions
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ENDOMETRIAL CANCER

Intervention / Treatment
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* Device: Surgery with UM
* Device: Surgery without UM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A subject will be considered eligible for inclusion in this study if all the following criteria are met: Patient must be greater than or equal to 18 years old. Suspected clinically early stage endometrial cancer of any histology (endometrioid, mixed, serous, clear-cell, carcinosarcomas, mucinous) Pre-operative imaging not suggestive of extra-uterine disease, if obtained pre-operatively. CA 125 testing is optional but, if obtained, must be within lab normal values. 5. ECOG performance status 0-2 (see appendix 1). 6. Signed informed consent and ability to comply with follow-up. 7. Per the opinion of the treating investigator, the patient must be a suitable candidate for the MIS surgical procedure. Exclusion Criteria: A subject must not have any of the following criteria: Planned laparotomic hysterectomy On progesterone therapy to treat their endometrial cancer Any prior pelvic irradiation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: A prospective multi-center non-inferiority randomized study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Surgery With UM (Arm MAN UA)<br>Subjects that undergo a MIS approach with a uterine manipulator (experimental arm) | Device: Surgery with UM<br>* The experimental group will have MIS with the placement of a uterine manipulator<br>|
| Active Comparator: Surgery Without UM (Arm Control)<br>Subjects that undergo a MIS approach without a uterine manipulator (control arm) | Device: Surgery without UM<br>* The control group will have MIS without the placement of a uterine manipulator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive peritoneal cytology (PC) | Positive PC is defined as the presence of malignant cells in the peritoneal cytology specimen. | Immediately after uterine manipulator placement in the manipulator group or prior to the initiation of the hysterectomy procedure in the non-manipulator group | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-operative positive PC | Positive PC is defined as the presence of malignant cells in the peritoneal cytology specimen. | Immediately after closure of the vaginal cuff | 
| Lymphovascular space invasion (LVSI) | LVSI is defined as the presence of tumor cells within a definite endothelial-lined space (lymphatics or blood vessels) at the advancing edge of the tumor as it invades the myometrium, within an endometrial polyp, or within the endometrial stroma. | During surgery | 
| Percentage of myometrial invasion (MI) | Defined as the % of invasion into the myometrium from the endomyometrial junction | During surgery | 
| Extent of lymph node metastases | Defined as presence of isolated tumor cells (ITC - <0.2 mm), or micrometastasis (mm - 0.2 - 2 mm), or macrometastasis (MM - > 2 mm), whichever is greater. | During surgery | 
| Operative time | Defined as time from start of operation to closure of skin in minutes as documented in the electronic medical record | 1 day | 
| Surgical morbidity | Surgical morbidity (CTCAE v5.0) grade 3 and higher, or any grade of the following adverse events: colonic fistula, colonic perforation, enterovesical fistula, gastrointestinal fistula, ileus, intra-abdominal hemorrhage, rectal fistula, rectal perforation, small intestinal perforation, abdominal infection, pelvic infection, vaginal infection, intra-operative arterial injury, venous injury, intra-operative gastrointestinal injury, intra-operative hemorrhage, intra-operative neurological injury, intra-operative urinary injury, and post-operative hemorrhage. | Intra-operative and up to 30 days post-surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endometrial, cancer, uterine, manipulator