Weight-loss Drug for Fertility-Sparing Treatment of Atypical Hyperplasia and Low-grade Cancer of the Endometrium

NCT ID: NCT06073184

Last Updated: 2025-06-10

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-31
• Study Completion Date: 2032-02-29

Brief Summary

The incidence of endometrial cancer is increasing at an alarming rate. This trend parallels the rising rate of obesity, the most significant risk factor for endometrial cancer. Young women with obesity and endometrial cancer or atypical hyperplasia who want to maintain their fertility are treated with progestin therapy, such as progestin intra-uterine device (pIUD), which is associated with a mediocre response rate and high recurrence rate, and does not address the underlying cause, obesity. Therefore, the investigators want to assess whether the addition of a weight-loss drug to pIUD will improve their oncologic, reproductive and metabolic outcomes.

Detailed Description

The research aims to answer the question: "Does the addition of a Glucose-dependent Insulinotropic Polypeptide (GIP)/Glucagon-like Peptide-1 (GLP-1) co-agonist to standard progestin treatment lead to a higher complete response rate compared to historical response rates using progestin alone in young patients with endometrial cancer/atypical hyperplasia who wish to preserve their fertility?".

This is a multicentre single arm open-label phase II clinical trial to assess the complete pathologic response as determined by endometrial sampling after 48 weeks of tirzepatide (GIP/GLP-1 co-agonist) and progestin therapy in patients with BMI ≥ 27 who have endometrial cancer/atypical hyperplasia and desire fertility preservation.

Conditions

Endometrial Cancer; Atypical Hyperplasia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tirzepatide and Progestin Intrauterine Device

All patients will receive a progestin intrauterine device and tirzepatide subcutaneous injections

Group Type: EXPERIMENTAL

Mounjaro

Intervention Type: DRUG

Weekly subcutaneous injection of 2.5mg tirzepatide at baseline with dose escalation by 2.5mg every 4 weeks to reach 15mg or the maximum tolerated dose, by Week 20

Mirena

Intervention Type: DRUG

Levonorgestrel-releasing Intrauterine System (52mg) to deliver up to 20 mcg levonorgestrel per day

Interventions

Mounjaro

Weekly subcutaneous injection of 2.5mg tirzepatide at baseline with dose escalation by 2.5mg every 4 weeks to reach 15mg or the maximum tolerated dose, by Week 20

Intervention Type: DRUG

Mirena

Levonorgestrel-releasing Intrauterine System (52mg) to deliver up to 20 mcg levonorgestrel per day

Intervention Type: DRUG

Other Intervention Names

Tirzepatide; Progestin-releasing intra-uterine device (pIUD)

Eligibility Criteria

Inclusion Criteria

• BMI ≥ 27
• Diagnosis of grade 1 or 2 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 co-morbidity with end-organ dysfunction
• Contraindications to pIUD or tirzepatide.
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 41 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rachel Soyoun Kim, MD

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Sarah E Ferguson, MD

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Central Contacts

Vanessa Ballin

Role: CONTACT

vanessa.ballin@uhn.ca

416-946-4501 ext. 3195

Other Identifiers

25-5042

Identifier Type: -

Identifier Source: org_study_id