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

NCT06073184 | Not Yet Recruiting Phase 2

• 1 other identifier: 25-5042
• Study Type: interventional
• Target: 71
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Endometrial Cancer; Atypical Hyperplasia

Keywords

Tirzepatide; pIUD

Outcome Measures

Primary Outcomes (1)

• Assessment of Complete Pathologic Response

  Proportion of patients (%) who achieve pathological complete response at 48 weeks after initiation of pIUD and tirzepatide.

  48 weeks

Secondary Outcomes (6)

• Assessment of Safety and Tolerability

  48 weeks

• Assessment of Feasibility

  2.5 years

• Assessment of Secondary Oncologic Outcomes

  6 years

• Assessment of Reproductive Outcomes

  6 years

• Assessment of Patient Reported Outcomes

  48 weeks

Study Arms (1)

Tirzepatide and Progestin Intrauterine Device

EXPERIMENTAL

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

Drug: Mounjaro; Drug: Mirena

Interventions

Mounjaro 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

Also known as: Tirzepatide

Tirzepatide and Progestin Intrauterine Device

Mirena DRUG

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

Also known as: Progestin-releasing intra-uterine device (pIUD)

Tirzepatide and Progestin Intrauterine Device

Eligibility Criteria

• Age: 18 Years - 41 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Health Network, Toronto: lead

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

Tirzepatide; Levonorgestrel

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Norgestrel; Norpregnenes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Rachel Soyoun Kim, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

• Sarah E Ferguson, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vanessa Ballin

CONTACT

416-946-4501; vanessa.ballin@uhn.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2023
• First Posted: October 10, 2023
• Study Start: August 1, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2032
• Last Updated: June 10, 2025

Record last verified: 2025-06