Uterine Manipulation During Minimally Invasive Surgery for Early Stage Endometrial Cancer (MAN-U)

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.

Study Overview

• Status: Recruiting
• Conditions: ENDOMETRIAL CANCER
• Intervention / Treatment: Device: Surgery with UM; Device: Surgery without UM

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 278
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anthony Costales, MD; Phone Number: 713-798-3495; Email: costales@bcm.edu
• Study Contact Backup: Name: Roberto Vargas, MD; Phone Number: 216-444-3414; Email: vargasr@ccf.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Suspended
      • Cleveland Clinic
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Baylor College of Medicine
      • Contact: Anthony Costales, MD; Phone Number: 713-798-3495; Email: costales@bcm.edu
    • Houston, Texas, United States, 77030
      • Recruiting
      • Ben Taub General Hospital
      • Contact: Anthony Costales, MD; Phone Number: 713-798-3495; Email: costales@bcm.edu
    • Houston, Texas, United States, 77030
      • Recruiting
      • Baylor College of Medicine- McNair Campus
      • Contact: Anthony Costales, MD; Phone Number: 713-798-3495; Email: costales@bcm.edu
    • Houston, Texas, United States, 77054
      • Recruiting
      • Harris Health System - Smith Clinic
      • Contact: Anthony Costales, MD; Phone Number: 713-798-3495; Email: costales@bcm.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

A subject will be considered eligible for inclusion in this study if all the following criteria are met:

1. Patient must be greater than or equal to 18 years old.
2. Suspected clinically early stage endometrial cancer of any histology (endometrioid, mixed, serous, clear-cell, carcinosarcomas, mucinous)
3. Pre-operative imaging not suggestive of extra-uterine disease, if obtained pre-operatively.
4. 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:

1. Planned laparotomic hysterectomy
2. On progesterone therapy to treat their endometrial cancer
3. Any prior pelvic irradiation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Anthony Costales, MD
• Collaborators: The Cleveland Clinic
• Investigators: Principal Investigator: Anthony Costales, MD, Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2021
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: October 7, 2020
• First Submitted That Met QC Criteria: October 7, 2020
• First Posted (Actual): October 14, 2020

Study Record Updates

• Last Update Posted (Estimated): October 15, 2025
• Last Update Submitted That Met QC Criteria: October 13, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: cancer; endometrial; uterine; manipulator
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Neoplasms; Neoplasms; Endometrial Neoplasms; Surgical Procedures, Operative
• Other Study ID Numbers: H-46373

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No