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

Sponsor
University Health Network, Toronto (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT06073184
Collaborator
(none)
90
Enrollment
1
Arm
60
Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
90 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
This is a multicentre single arm, historically controlled, open-label phase 2 study to assess the safety and efficacy of the combination of semaglutide and pIUDThis is a multicentre single arm, historically controlled, open-label phase 2 study to assess the safety and efficacy of the combination of semaglutide and pIUD
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Weight-loss Drug for Fertility-Sparing Treatment of Atypical Hyperplasia and Grade 1 Cancer of the Endometrium (WE-FiERCE)
Anticipated Study Start Date :
Jan 1, 2024
Anticipated Primary Completion Date :
Jan 1, 2025
Anticipated Study Completion Date :
Jan 1, 2029

Arms and Interventions

Arm Intervention/Treatment
Experimental: Single arm

Treatment offered as part of this study will be semaglutide in addition to pIUD for total of 12 months.

Drug: Ozempic
Semaglutide injection, 2mg once weekly.
Other Names:
  • Semaglutide

    • Drug: Mirena
    Levonorgestrel-releasing Intrauterine System (52mg) to deliver up to 20 mcg levonorgestrel per day
    Other Names:
  • Progestin-releasing intra-uterine device (pIUD)

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Complete Response Rate (CRR) at 6 months [6 months]

      Proportion of patients who achieve pathological complete response at 6 months after initiation of pIUD and semaglutide (%).

    Secondary Outcome Measures

    1. CRR at 12 months: proportion of patients who achieve pathological complete response at 12 months after initiation of pIUD and semaglutide (%) [60 months]

    2. Time to achieve complete response: time it takes for the endometrium to return to normal (weeks) [60 months]

    3. Duration of response: duration of complete response (weeks) [60 months]

    4. Overall recurrence rate: proportion of patients who achieve pathological complete response but experience a recurrence (%) [60 months]

    5. Time to recurrence after complete response (weeks) [60 months]

    6. Overall progression/persistence rate: proportion of patients who experience progression or persistence (%) [60 months]

    7. Frequency of residual disease on definitive surgical specimens: proportion of patients with residual disease after they undergo completion hysterectomy (%) [60 months]

    8. Pregnancy rate (# of pregnancies/total attempting pregnancy) [60 months]

    9. Live birth rate (live births/total attempting pregnancy) [60 months]

    10. Incidence of Treatment-Emergent Adverse Events [60 months]

    11. Endometrial Cancer Specific Health Related Quality of Life Questionnaire (FACT-EN) [60 months]

    12. Impact of Weight on Quality of Life (IWQOL) scale [60 months]

    13. Generalized Anxiety Disorder 7-item (GAD-7) scale [60 months]

    14. Patient Health Questionnaire (PHQ-9) scale [60 months]

    15. Adapted Illness Intrusiveness Scale (IIRS) [60 months]

    16. Reproductive Concerns After Cancer (RCAC) scale [60 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 41 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. People aged ≥ 18 and ≤ 41 years of age

    2. BMI ≥ 27

    3. Diagnosis of grade 1 endometrioid EC or AH

    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) MLH1 with methylation EC

    5. History of other malignancies, except if:

    1. Curatively treated with no evidence of disease for >5 years

    1. Previous bariatric surgery

    2. Current use of weight loss medication

    3. Medical co-morbidity with end-organ dysfunction

    4. Unable to understand and participate in the informed consent process

    5. Currently pregnant or breastfeeding (negative serum bhCG at screening)

    6. Contraindications to progestin intra-uterine device (pIUD)

    7. Self-reported change in body weight of >5kg within 90 days before screening

    8. Previous treatment with any medication for obesity within 90 days before screening

    9. History of chronic pancreatitis or acute pancreatitis within 180 days prior to screening

    10. Contraindications to semaglutide

    11. Personal or first-degree history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma

    12. Anaphylactic reaction to semaglutide

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • University Health Network, Toronto

    Investigators

    • Principal Investigator: Rachel Soyoun Kim, MD, University Health Network, Toronto
    • Principal Investigator: Sarah E Ferguson, MD, University Health Network, Toronto

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    University Health Network, Toronto
    ClinicalTrials.gov Identifier:
    NCT06073184
    Other Study ID Numbers:
    • WE-FiERCE
    First Posted:
    Oct 10, 2023
    Last Update Posted:
    Oct 10, 2023
    Last Verified:
    Oct 1, 2023
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by University Health Network, Toronto
    Semaglutide
    pIUD
    Additional relevant MeSH terms:
    Endometrial Neoplasms
    Weight Loss
    Hyperplasia
    Progestins

    Study Results

    No Results Posted as of Oct 10, 2023