Orlistat Plus Progestin for Fertility-Sparing Treatment of Endometrial Cancer or Atypical Hyperplasia

Summary

This is a single-center, randomized, open-label, controlled clinical trial evaluating whether adding orlistat to standard progestin therapy can improve treatment response in patients receiving fertility-sparing treatment for early-stage endometrial cancer (grade 1-2) or atypical endometrial hyperplasia. Progestin is the standard drug used to preserve the uterus and fertility in these patients, but about 30% of patients respond poorly because the progesterone receptor (PR) in the endometrium is lost or reduced. Laboratory studies by the research team have shown that orlistat, a widely used oral weight-loss drug that blocks fat absorption, can raise PR levels and restore sensitivity to progestin. The study will enroll 48 patients (age 45 years or younger, body mass index 24 kg/m2 or higher) who still have residual disease and low PR expression after at least 3 months of first-line progestin therapy. Participants will be randomly assigned in a 1:1 ratio to receive either progestin plus orlistat (experimental group) or progestin alone (control group) for 3 months, followed by 24 months of follow-up. The main goal is to compare the change in PR expression from baseline after 3 months of treatment. The study will also assess how many patients achieve complete disease reversal, time to complete response, recurrence, pregnancy and live-birth rates, safety, and changes in body weight and metabolic measures.

Timeline

Start

2026-07

Primary completion

2027-09

Completion

2029-12

Drugs

Indications