Uterine Preservation Via Lifestyle Transformation

The Washington University

Status and phase: Enrolling; Phase 2

Conditions: Grade 1 Endometrial Cancer; Endometrial Hyperplasia

Treatments: Drug: Progestin; Behavioral: Telemedicine behavioral weight intervention; Drug: Levonorgestrel-releasing IUD.; Behavioral: Enhanced usual care

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05903131

P50CA265793 (U.S. NIH Grant/Contract)

202307204

Details and patient eligibility

About

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.

Enrollment: 96 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 documented.

• 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.

• Undergoing uterine-sparing management (e.g. due to interest in fertility preservation, interest in uterine preservation, provider recommendation, or other reason).

• 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.

• 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.
• Pregnant and/or breastfeeding. Participants must have a negative urine or serum pregnancy test during screening window and within 7 days prior to LNG-IUD insertion. If LNG-IUD is in place, lack of pregnancy is assumed.
• Active pelvic infection at the time of IUD placement or other contraindication to the use of an IUD in the opinion of the treating physician.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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96 participants in 2 patient groups

Arm 1: Levonorgestrel-releasing IUD (LNG-IUD) + Behavioral Weight Loss Intervention

Experimental group

Description:

* 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.

Treatment:

Drug: Levonorgestrel-releasing IUD.

Behavioral: Telemedicine behavioral weight intervention

Drug: Progestin

Arm 2: Levonorgestrel-releasing IUD (LNG-IUD) + Enhanced Usual Care

Active Comparator group

Description:

* 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.

Treatment:

Behavioral: Enhanced usual care

Drug: Levonorgestrel-releasing IUD.