Uterine Preservation Via Lifestyle Transformation

Official title

UPLifT-Endo: Uterine Preservation Via Lifestyle Transformation A Behavioral Intervention to Promote Primary Prevention and Uterine Preservation in Premenopausal Women With Obesity and Atypical Endometrial Hyperplasia or Grade 1 Endometrial Cancer

Overview

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.

Interventions

• 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.
• Behavioral Enhanced usual care
  1-3 page handouts
• Drug Levonorgestrel-releasing IUD.
  Standard of care

Primary outcome measures

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

Secondary outcome measures (6)

• Time to resolution of atypical endometrial hyperplasia (AEH) [Time frame: Through completion of follow-up (estimated to be 2 years)]
• Time to resolution of endometrial cancer [Time frame: Through completion of follow-up (estimated to be 2 years)]
• Atypia-free survival [Time frame: Through completion of follow-up (estimated to be 2 years)]
• Endometrial cancer progression-free survival (EC-PFS) [Time frame: Through completion of follow-up (estimated to be 2 years)]
• Change in weight [Time frame: Through completion of follow-up (estimated to be 2 years)]
• 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)]

Eligibility 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 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 3 centers

• Washington University School of Medicine — St Louis
• University of New Mexico — Albuquerque
• University of Oklahoma — Oklahoma City

Identifiers

NCT: NCT05903131 · 202307204 · P50CA265793

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗