Endometrial Cancer, Atypical Hyperplasia, Fertility Perservation
Conditions
Keywords
pIUD, semaglutide, WEGOVY, atypical hyperplasia, endometrial cancer, fertility preservation
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 Glucagon-like Peptide-1 (GLP-1) 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 semaglutide (GLP-1) and progestin therapy in patients with BMI ≥ 27 who have endometrial cancer/atypical hyperplasia and desire fertility preservation.
Interventions
DRUGWegovy
Weekly subcutaneous injection of 0.25 mg semaglutide at baseline with dose escalation every 4 weeks to reach 2.4 mg or the maximum tolerated dose, by Week 16
DRUGMirena
Levonorgestrel-releasing Intrauterine System (52mg) to deliver up to 20 mcg levonorgestrel per day
Sponsors
GynOncTrials
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 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 comorbidity with end-organ dysfunction * History of suicide attempts or current suicidal thoughts or behaviours * Currently taking insulin or insulin secretagogue (e.g., sulfonylurea) * Diabetic retinopathy * Gastroparesis or problems with food digestion * History of tachycardia (e.g., sinus tachycardia, supraventricular tachycardia, atrial fibrillation, atrial flutter, or ventricular tachycardia) * Contraindications to pIUD or semaglutide. * Hypersensitive to WEGOVY or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container * Personal or family history of medullary thyroid carcinoma (MTC) * Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) * Pregnant or breast-feeding * Current or recurrent pelvic inflammatory disease * Lower genital tract infection * Postpartum endometritis * Uterine anomalies including fibroids if they distort the uterine cavity * Cervical malignancy * Known or suspected progestin-dependent neoplasia, including breast cancer * Cervicitis * Untreated cervical dysplasia * Active liver disease or dysfunction * Actual benign or malignant liver tumors * Sceptic abortion within the previous three months * Hypersensitivity to levonorgestrel or any of the other ingredients in the formulation or components of MIRENA. * Bacterial endocarditis * Established immunodeficiency * Acute malignancies affecting blood or leukemias * Recent trophoblastic disease while hCG levels are elevated * Previously inserted intrauterine device (IUD) that has not been removed * Conditions associated with increased susceptibility to pelvic infections * 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 semaglutide. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Safety and Tolerability | 48 weeks | Adverse events during treatment period |
| Assessment of Feasibility | 1.5 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 |
Countries
Canada
Contacts
CONTACTVanessa Ballin
PRINCIPAL_INVESTIGATORRachel Soyoun Kim, MD
University Health Network, Toronto
PRINCIPAL_INVESTIGATORSarah E Ferguson, MD
University Health Network, Toronto
Outcome results
None listed