Weight-loss Drug for Fertility-Sparing Treatment of Atypical Hyperplasia and Grade 1 Cancer of the Endometrium (WE-FiERCE)

WE-FiERCE

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.

2024-09-01

2028-09-01

2031-09-01

Not yet recruiting

Early phase I

108

Inclusion Criteria: 1. People aged ≥ 18 and ≤ 41 years of age 2. BMI ≥ 27 3. Diagnosis of grade 1 or 2 endometrioid EC or AH made by either endometrial biopsy or dilation and curettage 4. Clinical FIGO 2009 stage 1A disease - no evidence of metastatic disease beyond the uterus and no evidence of myometrial invasion by imaging performed (MRI, CT) 5. ECOG status \<2 6. Desire for fertility preservation 7. Have signed an approved informed consent form Exclusion Criteria: 1. Evidence of myometrial invasion or extra-uterine disease on imaging 2. High grade or p53 mutated (p53mut) EC 3. Estrogen receptor (ER) EC 4. Mismatch repair deficient (MMRd) EC 5. History of other malignancies, except if: a. Curatively treated with no evidence of disease for \>5 years 6. Previous surgical treatment of obesity 7. Current use of weight loss medication (no use in last 6 months) 8. Medical co-morbidity with end-organ dysfunction 9. Unable to understand and participate in the informed consent process 10. Currently pregnant or breastfeeding (negative serum bhCG at screening) 11. Contraindications to progestin intra-uterine device (pIUD) 12. History of chronic pancreatitis or acute pancreatitis within 180 days prior to screening 13. Contraindications to tirzepatide 1. Personal or first-degree history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma 2. Anaphylactic reaction

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'This is a prospective, randomized, open label, multicentre, phase II, non-comparative study to determine the efficacy and safety of a GLP-1R/GIPR coagonist in combination with standard pIUD in patients with EC/AH who wish to preserve their fertility.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 108, 'type': 'ESTIMATED'}}

2024-03-19