Endometrial Cancer, Atypical Hyperplasia
Conditions
Keywords
Tirzepatide, pIUD
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.
Interventions
Sponsors
University Health Network, Toronto
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 41 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 Safety and Tolerability | 48 weeks | Adverse events during treatment period |
| 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 |
| Assessment of Reproductive Outcomes | 6 years | Rate of pregnancy; Live birth; Miscarriage; Pregnancy complications |
Contacts
Primary ContactVanessa Ballin
Outcome results
None listed