Weight-loss Drug for Fertility-Sparing Treatment of Atypical Hyperplasia and Grade 1 Cancer of the Endometrium
- Conditions
- Endometrial CancerAtypical Hyperplasia
- Interventions
- Registration Number
- NCT06073184
- Lead Sponsor
- University Health Network, Toronto
- 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- Female
- Target Recruitment
- 71
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Tirzepatide and Progestin Intrauterine Device Mounjaro All patients will receive a progestin intrauterine device and tirzepatide subcutaneous injections Tirzepatide and Progestin Intrauterine Device Mirena All patients will receive a progestin intrauterine device and tirzepatide subcutaneous injections
- Primary Outcome Measures
Name Time Method Assessment of Complete Pathologic Response 48 weeks Proportion of patients (%) who achieve pathological complete response at 48 weeks after initiation of pIUD and tirzepatide.
- Secondary Outcome Measures
Name Time Method Assessment of Safety and Tolerability 48 weeks Adverse events during treatment period
Assessment of Feasibility 2.5 years Rate of accrual; Patient compliance; Retention
Assessment of Secondary Oncologic Outcomes 6 years Time to achieve complete response; Duration of response; Recurrence rate; Time to recurrence; Progression/persistence rate
Assessment of Reproductive Outcomes 6 years Rate of pregnancy; Live birth; Miscarriage; Pregnancy complications
Assessment of Patient Reported Outcomes 48 weeks Quality of Life; Psychological functioning and fertility concerns after cancer diagnosis
Assessment of Metabolic Outcomes 48 weeks Weight; BMI; Waist/hip circumference; Serum biomarkers of obesity and insulin resistance