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

Endometrial Cancer Clinical Trial

— WE-FiERCE  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06073184
• Other study ID #: WE-FiERCE
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: September 2024
• Est. completion date: September 2031

Study information

• Verified date: March 2024
• Source: University Health Network, Toronto
• Contact: Vanessa Ballin
• Phone: 416-946-4501
• Email: vanessa.ballin[@]uhn.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The research aims to answer the question: "Does the addition of Glucagon-like Peptide-1 (GLP-1) 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, historically controlled, open-label phase 2 study to assess the safety and efficacy of the combination of semaglutide (GLP-1) and pIUD.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 108
• Est. completion date: September 2031
• Est. primary completion date: September 2028
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 41 Years

Eligibility

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

Related Conditions & MeSH terms

• Atypical Hyperplasia
• Endometrial Cancer
• Endometrial Neoplasms
• Hyperplasia
• Weight Loss

Intervention

Drug:
• Mounjaro
Tirzepatide injection, starting dose is 2.5mg injected subcutaneously once weekly. After 4 weeks, dose should be increased to 5mg once weekly. The dose then can be increased in 2.5mg increments after no less than 4 weeks on current dose to maximum dose of 15mg once weekly.
• Mirena
Levonorgestrel-releasing Intrauterine System (52mg) to deliver up to 20 mcg levonorgestrel per day

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Response Rate (CRR) at 48 weeks	Proportion of patients (%) who achieve pathological complete response at 48 weeks after initiation of pIUD and tirzepatide.	48 weeks
Secondary	Complete Response Rate (CRR) at 36 months		36 months
Secondary	Time to achieve complete response: time it takes for the endometrium to return to normal (months)		36 months
Secondary	Duration of response: duration of complete response (years)		7 years
Secondary	Overall recurrence rate: proportion of patients who achieve pathological complete response but experience a recurrence (%)		7 years
Secondary	Time to recurrence after complete response (months)		36 months
Secondary	Overall progression/persistence rate: proportion of patients who experience progression or persistence (%)		36 months
Secondary	Frequency of residual disease on definitive surgical specimens: proportion of patients with residual disease after they undergo completion hysterectomy (%)		7 years
Secondary	Pregnancy rate (# of pregnancies/total attempting pregnancy)		7 years
Secondary	Live birth rate (live births/total attempting pregnancy)		7 years
Secondary	Pregnancy Complications		7 years
Secondary	Incidence of Treatment-Emergent Adverse Events		36 months
Secondary	Endometrial Cancer Specific Health Related Quality of Life Questionnaire (FACT-EN)		48 weeks
Secondary	Impact of Weight on Quality of Life (IWQoL-Lite)		48 weeks
Secondary	Generalized Anxiety Disorder 7-item (GAD-7)		48 weeks
Secondary	Patient Health Questionnaire (PHQ-9)		48 weeks
Secondary	Reproductive Concerns After Cancer (RCAC)		48 weeks
Secondary	Adapted Illness Intrusiveness Scale (IIRS)		48 weeks