A Behavioral Intervention to Promote Primary Prevention and Uterine Preservation in Premenopausal Women With Obesity and Endometrial Hyperplasia

• ClinicalTrials.gov Identifier: NCT05903131
• Recruitment Status: Not yet recruiting
• First Posted: June 15, 2023
• Last Update Posted: May 14, 2024
• Sponsor: Washington University School of Medicine
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Washington University School of Medicine

Study Description

Brief Summary:

Up to 60% of endometrial cancer cases are attributed to obesity, in part because obesity promotes development of atypical endometrial hyperplasia (AEH), and up to 40% of women with AEH go on to develop endometrial cancer. The increasing prevalence of obesity in premenopausal women has resulted in increasing rates of AEH in this age group. Hysterectomy with removal of the fallopian tubes and ovaries is 100% effective in preventing endometrial cancer, but this approach results in infertility. Fertility-sparing treatments exist, such as treatment with oral or intrauterine progestin, but these treatments do not work uniformly and do not combat the underlying cause of endometrial cancer, which is obesity and metabolic syndrome. Additionally, up to 41% of women on progestin eventually experience relapse of AEH or endometrial cancer. Third, many patients have insulin resistance that may worsen with progestin therapy. Thus, to improve treatment of AEH and grade 1 endometrial cancer, prevent and reverse endometrial cancer, and allow women to preserve their fertility, the investigators must integrate an effective weight loss strategy to be given with progestin treatment. It is the hypothesis that premenopausal women with AEH desire uterine preservation will be more likely to have atypia-free uterine preservation at one year if they receive progestin in combination with a behavioral weight loss intervention versus progestin plus enhanced usual care.

Condition or disease	Intervention/treatment	Phase
Endometrial Hyperplasia; Grade 1 Endometrial Cancer	Behavioral: Telemedicine behavioral weight intervention; Drug: Progestin; Behavioral: Enhanced usual care; Drug: Levonorgestrel-releasing IUD.	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 96 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Behavioral Intervention to Promote Primary Prevention and Uterine Preservation in Premenopausal Women With Obesity and Endometrial Hyperplasia
• Estimated Study Start Date: June 30, 2024
• Estimated Primary Completion Date: June 30, 2028
• Estimated Study Completion Date: June 30, 2029

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm 1: Levonorgestrel-releasing IUD (LNG-IUD) + Behavioral Weight Loss Intervention; The levonorgestrel-releasing IUD is used in this study as per standard care.; The behavioral weight loss intervention consists of a telemedicine cognitive behavioral coaching program. At each session, patients will self-report weight, number of days they kept a food journal during the past week, average daily caloric intake for the week, number of days exercised for the week, total number of minutes of moderate physical activity, and average number of steps per day for the week.	Behavioral: Telemedicine behavioral weight intervention; Weekly telephone calls during the first month, biweekly during the next 5 months, and then monthly for the last 7 months (12 months total). Each telephone session will be 30 minutes long.; Drug: Progestin; Released via the levonorgestrel-releasing IUD.; Drug: Levonorgestrel-releasing IUD.; Standard of care
Active Comparator: Arm 2: Levonorgestrel-releasing IUD (LNG-IUD) + Enhanced Usual Care; The levonorgestrel-releasing IUD is used in this study as per standard care.; Participants will be provided with 1- to 3-page handouts on topics including healthy eating, exercise, and behavioral eating strategies from materials provided on the American Cancer Society, Society of Gynecologic Oncology, and WebMD Nourish websites. These materials encourage weight loss through calorie counting, recording dietary intake, engaging in exercise programs, and using portion control strategies.; The participants randomized to this arm will cross over to the behavioral weight loss intervention arm at 12 months if they have not achieved resolution of AEH or grade 1 endometrial cancer.	Behavioral: Enhanced usual care; 1-3 page handouts; Drug: Levonorgestrel-releasing IUD.; Standard of care

Outcome Measures

Primary Outcome Measures :

1. Number of participants with atypical endometrial hyperplasia (AEH)-free biopsy [ Time Frame: At 1 year ]

Secondary Outcome Measures :

1. Time to resolution of atypical endometrial hyperplasia (AEH) [ Time Frame: Through completion of follow-up (estimated to be 2 years) ]
   Defined as the period of time in months/days from the first biopsy to show AEH or grade 1 endometrial cancer to the first biopsy that shows no evidence of hyperplasia or malignancy
2. Time to resolution of endometrial cancer [ Time Frame: Through completion of follow-up (estimated to be 2 years) ]
3. Atypia-free survival [ Time Frame: Through completion of follow-up (estimated to be 2 years) ]
   -Defined as the time interval from the date of positive treatment response (as determined by biopsy) to the date of atypical endometrial hyperplasia (AEH) recurrence. AEH-free or the patients with lost to follow-up will be censored at the last follow-up.
4. Endometrial cancer progression-free survival (EC-PFS) [ Time Frame: Through completion of follow-up (estimated to be 2 years) ]
   EC-PFS is defined as the time interval from the date of positive treatment response (as determined by biopsy) to the date of recurrence of EC. Endometrial cancer-free patients or the patients with lost to follow-up will be censored at the last follow-up.
5. Change in weight [ Time Frame: Through completion of follow-up (estimated to be 2 years) ]
6. Change in Cancer Worry Impact Events Scale (CWIES) [ Time Frame: At enrollment, 6 months, 12 months, end of intervention, and 24 months (estimated to be 2 years) ]
   The CWIES is a 15-item self-report measure evaluating stress reactions and traumatic experiences, specifically inquiring about cancer worry-specific distress. Range of values for each individual item will be a Likert Scale from 0-5. 0=not at all and 5=often. The higher the score, the more cancer-worry specific distress the participant has.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Diagnosis of histologically confirmed complex atypical endometrial hyperplasia (AEH) or grade 1 endometrial cancer.

  • Patients with a previous diagnosis of AEH or grade 1 endometrial cancer who are already being followed with conservative management with oral or LNG-IUD progestin therapy are eligible.
  • For patients with a previous diagnosis of AEH or grade 1 endometrial cancer who have been placed on progestin prior to study entry, the duration of IUD or oral progestin use prior to trial entry should be less than or equal to 6 months.
• Premenopausal woman with a uterus.
• ECOG performance status of 0-2.
• At least 18 years of age and no more than 45 years of age.
• Interested in uterine preservation/fertility-sparing treatment.
• BMI ≥ 30 kg/m^2.
• Prior or current receipt of progestin is allowed as above. Willingness to undergo placement of LNG-IUD at the time of study entry.
• Prior or current receipt of metformin is allowed.
• Ability to understand and willingness to sign an IRB approved written informed consent document.

Exclusion Criteria:

• Current, active treatment for any malignant neoplasm with chemotherapy or radiation.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
• Pregnant and/or breastfeeding. Participants must have a negative serum pregnancy test within 7 days of date of registration.

• Contraindication to use of an IUD:

  • Congenital or acquired uterine anomaly, including fibroids if they distort the uterine cavity
  • PID, postpartum endometriosis, infected abortion in the last 3 months, acute cervicitis or vaginitis including bacterial vaginosis
  • Acute liver disease, liver tumor (benign or malignant)
  • Hypersensitivity to any component of the IUD (levonorgestrel, silicone, polyethylene)
  • Known or suspected carcinoma of the breast.

Contacts and Locations

Contacts

Contact: Andrea R Hagemann, M.D., MSCI; 314-362-1763; hagemanna@wustl.edu

Locations

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

Contact: Andrea R Hagemann, M.D., MSCI 314-362-1763 hagemanna@wustl.edu

Principal Investigator: Andrea R Hagemann, M.D., MSCI

Sub-Investigator: Graham Colditz, M.D., DrPH

Sub-Investigator: Ian Hagemann, M.D., Ph.D.

Sub-Investigator: David Mutch, M.D.

Sub-Investigator: Esther Lu, Ph.D.

Sub-Investigator: Gary Patii, Ph.D.

Sub-Investigator: David Morris, Ph.D.

United States, New Mexico

University of New Mexico

Albuquerque, New Mexico, United States, 87106

Contact: Carolyn Muller, M.D. 505-272-2111

Principal Investigator: Carolyn Muller, M.D.

Sub-Investigator: Kimberly Leslie, M.D.

United States, Oklahoma

University of Oklahoma

Oklahoma City, Oklahoma, United States, 73104

Contact: Kathleen Moore, M.D., MS 405-271-8707

Principal Investigator: Kathleen Moore, M.D., MS

Sponsors and Collaborators

Washington University School of Medicine

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Andrea R Hagemann, M.D., MSCI; Washington University School of Medicine

More Information

Additional Information:

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine 

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT05903131
• Other Study ID Numbers: 202307204; P50CA265793 ( U.S. NIH Grant/Contract )
• First Posted: June 15, 2023
• Last Update Posted: May 14, 2024
• Last Verified: May 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Washington University School of Medicine:

fertility-sparing; weight management; obesity; endometrial cancer; behavioral intervention; premenopausal endometrial hyperplasia; premenopausal endometrial cancer

Additional relevant MeSH terms:

Endometrial Neoplasms; Endometrial Hyperplasia; Obesity; Hyperplasia; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Pathologic Processes; Levonorgestrel; Progestins; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Physiological Effects of Drugs; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral; Hormones