Weight-loss drug plus progestin for fertility-sparing endometrial hyperplasia/cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This multicentre, single-arm phase II study evaluates whether semaglutide combined with a progestin intrauterine device improves complete pathologic response after 48 weeks in women with BMI ≥27 who have early, fertility-desiring endometrial cancer or atypical hyperplasia. Participants receive Wegovy and a Mirena IUD and undergo endometrial sampling to determine response. The study aims to address oncologic, reproductive, and metabolic outcomes beyond standard progestin therapy alone. Eligible patients include those with low-grade disease confined to the uterus and a desire to preserve fertility, while key exclusions include myometrial invasion, extrauterine disease, and certain molecular risk factors.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* BMI ≥ 27
* Diagnosis of grade 1 endometrioid endometrial cancer or atypical hyperplasia made by either endometrial biopsy or dilation and curettage
* For those with endometrial cancer, clinical FIGO 2009 stage 1A disease without evidence of metastatic disease beyond the uterus and no myometrial invasion by MRI or CT
* ECOG status \<2
* Desire for fertility preservation
* Ability to understand and willing to sign a written informed consent document

Exclusion Criteria:

* Evidence of myometrial invasion or extra-uterine disease on imaging
* High grade or p53 mutated (p53mut) endometrial cancer
* Estrogen receptor negative endometrial cancer (positivity defined as moderate/strong staining\>10%)
* Mismatch repair deficient (MMRd) endometrial cancer
* History of other malignancies except if curatively treated with no evidence of disease for \>5 years
* Previous surgical treatment of obesity
* Current use of weight loss medication (no use in last 2 months)
* Medical comorbidity with end-organ dysfunction
* History of suicide attempts or current suicidal thoughts or behaviours
* Currently taking insulin or insulin secretagogue (e.g., sulfonylurea)
* Diabetic retinopathy
* Gastroparesis or problems with food digestion
* History of tachycardia (e.g., sinus tachycardia, supraventricular tachycardia, atrial fibrillation, atrial flutter, or ventricular tachycardia)
* Contraindications to pIUD or semaglutide.

  * Hypersensitive to WEGOVY or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container
  * Personal or family history of medullary thyroid carcinoma (MTC)
  * Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
  * Pregnant or breast-feeding
  * Current or recurrent pelvic inflammatory disease
  * Lower genital tract infection
  * Postpartum endometritis
  * Uterine anomalies including fibroids if they distort the uterine cavity
  * Cervical malignancy
  * Known or suspected progestin-dependent neoplasia, including breast cancer
  * Cervicitis
  * Untreated cervical dysplasia
  * Active liver disease or dysfunction
  * Actual benign or malignant liver tumors
  * Sceptic abortion within the previous three months
  * Hypersensitivity to levonorgestrel or any of the other ingredients in the formulation or components of MIRENA.
  * Bacterial endocarditis
  * Established immunodeficiency
  * Acute malignancies affecting blood or leukemias
  * Recent trophoblastic disease while hCG levels are elevated
  * Previously inserted intrauterine device (IUD) that has not been removed
  * Conditions associated with increased susceptibility to pelvic infections
* Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.

Where it's running

• Princess Margaret Cancer Centre, University Health Network
  Toronto, Ontario, Canada Recruiting

Study contacts

• Principal investigator: Rachel Soyoun Kim, MD — University Health Network, Toronto
• Study coordinator: Vanessa Ballin
• Email: vanessa.ballin@uhn.ca
• Phone: 416-946-4501

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Other studies for the same condition or treatment. Recruiting studies are listed first.

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.