A clinical trial studying the effect of Tirzepatide in women living with endometrial cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University College Dublin

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-04-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

The Ludwig Cancer Institute, Princeton University, New Jersey, USA

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The proportion (%) of patients with a pCR in each group 12 months (Visit 14, 52 weeks ±14 days) post randomization.

Secondary objectives 5

1. The mean percentage fasting weight loss at 12 months (Visit 14, 52 weeks ±14 days) post randomization.
2. The change in Ki-67 PI 12 months (Visit 14, 52 weeks ±14 days) post randomization.
3. Quality of life assessment.
4. Safety The proportion of patients who develop progressive disease during the trial at 6 and 12 months.
5. Progression to surgery - The proportion of patients who progress to surgical management of endometrial cancer ie. hysterectomy following weight loss

Conditions and MedDRA coding

Endometrial adenocarcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Histologically confirmed FIGO grade 1 or 2 endometrioid adenocarcinoma on a curette or endometrial biopsy, p53 WT, MMR proficient.
2. Negative serum pregnancy test in pre-menopausal women and women < 2 years after the onset of menopause
3. No LNG-IUS or LNG-IUS inserted < 6 weeks prior to enrolment
4. Subjects must be able and willing to give written informed consent and to comply with the requirements of this study protocol
5. Females with a BMI > 27 kg/m2 at high risk of surgical complications due to co-morbidities (diabetes, hypertension, cardiovascular disease, obstructive sleep apnoea) or BMI > 30 kg/m2 with no comorbidities and who are at risk of surgical complications or have decided not to opt for immediate surgical intervention (having been advised that this is the standard of care).
6. Over 18 years of age at time of randomisation
7. CT scan of pelvis, abdomen and chest (or chest X-Ray) suggesting the absence of extrauterine disease in patients with endometrial cancer only
8. Myometrial invasion on MRI of not more than 50%
9. No lymph vascular invasion on biopsy.
10. Serum CA125 ≤30 U/mL.
11. No known hypersensitivity or contraindications for LNG-IUS (severe liver disease, personal history of breast cancer, active pelvic inflammatory disease, congenital uterine abnormality) or GLP-1 agonist
12. Ability to comply with endometrial biopsies at specified 3 monthly intervals
13. Inclusion of patients, who in the opinion of the gynaecological multidisciplinary team, at screening, are not suitable candidates for radiotherapy.

Exclusion criteria 34

1. ECOG performance status ≥3
2. Evidence of extra-uterine extension on cross sectional imaging
3. Congenital or acquired uterine anomaly which distorts the uterine cavity
4. Acute pelvic inflammatory disease and/or untreated sexually transmitted diseases and genital infections
5. Genital actinomycosis
6. History of pancreatitis
7. Diagnosis of Type 1 diabetes
8. Previous treatment with GLP-1 receptor agonists within the last 3 months
9. Visit 1 thyroid-stimulatory hormone (TSH) outside of the range of 0.4-6.0 mIUl-1
10. Obesity induced by other endocrine disorders (e.g., Cushing syndrome)
11. Current or history of treatment with medications that may cause significant weight gain within 3 months prior to screening visit, including systemic corticosteroids (except for a short course of treatment, i.e., 7-10 days), promtri-cyclic antidepressants, atypical antipsychotic and mood stabilisers (e.g., imipramine, amitriptyline, mirtazapine, phenelzine, chlorpromazine, thioridazine, clozapine, olanzapine, valproic acid and its derivatives, and lithium)
12. Grade 1 or 2 endometrioid adenocarcinoma of the endometrium with myometrial invasion deeper than 50% on MRI or any patients with grade 3 endometrioid adenocarcinoma
13. Participation in a clinical trial of weight control within the last 3 months prior to screening for this trial
14. Previous surgical treatment for obesity (excluding liposuction if performed >1 year before study entry)
15. History of major depressive disorder or a PHQ-9 >15 within the last 2 years (completed at visit 1) or history of other severe psychiatric disorders (e.g., schizophrenia or bipolar disorder) or diagnosis of an eating disorder such as restrained eating, binge eating, or bulimia (based on Questionnaire for Diagnosing Binge Eating Disorder and Bulimia Nervosa completed at visit 1)
16. Participants with a lifetime history of a suicide attempt or history of any suicidal behaviour within the past month before entry into the trial
17. Surgery scheduled for the trial duration period, except for minor surgical procedures, at the discretion of the Investigator
18. Impaired liver function, defined as screening aspartate aminotransferase or alanine aminotransferase ≥ 2.5 times upper normal range (one re-test analyzed at the local laboratory within 1 week prior to screening is permitted with the last sample being conclusive)
19. Impaired renal function defined as eGFR <90mL/min/1.73L2 (1 retest within 1 week prior to screening through the local laboratory is permitted with the result of the last sample conclusive)
20. Known clinically significant active cardiovascular disease, including history of unstable angina, acute coronary event, other significant cardiac events (including history of arrhythmias, myocardial infarction (MI), or conduction delays on electrocardiogram [ECG]), or cerebral stroke within the past 6 months and/or heart failure (New York Heart Association [NYHA] Class III or IV) at the discretion of the Investigator
21. Uncontrolled treated/untreated hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥80 mmHg). If white-coat hypertension is suspected at the screening visit a repeated measurement at run-in prior to other trial-related activities is allowed
22. Known or suspected abuse of alcohol or narcotics
23. MMR deficient or p53 mutated endometrial cancer.
24. Language barrier, mental incapacity, unwillingness or ability to understand and being able to complete the mental health questionnaire in the provided language
25. History of breast, thyroid or colon cancer
26. Current other cancer (past or present, except basal cell skin cancer or squamous cell skin cancer)
27. Breastfeeding mothers
28. Histological (cell) type other than endometrioid adenocarcinoma (sarcomas or high risk endometrial e.g. papillary serous, clear cell)
29. Pregnant or planning to become pregnant during trial period
30. Prior treatment for EAC
31. Patients with a history of pelvic or abdominal radiotherapy
32. Unwilling to have additional endometrial biopsies or unable to attend monthly clinical assessments
33. Unable to provide informed consent or complete questionnaires
34. Participants with a history of severe gastrointestinal disease, gastroparesis or significant dysmotility, or prior aspiration with anaesthesia

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The proportion (%) of patients with a pCR in each group 12 months (52 weeks ±14 days) post randomisation. pCR will be defined as the absence of any EAC or endometrial hyperplasia on endometrial biopsy using a H&E slide assessed by an independent pathologist after 12 months (Visit 14, 52 weeks ±14 days) of treatment.

Secondary endpoints 5

1. The mean percentage fasting weight loss at 12 months (Visit 14, 52 weeks ±14 days) post randomization.
2. The change in Ki-67 PI 12 months (Visit 14, 52 weeks ±14 days) post randomization.
3. Quality of life assessment at baseline (day -30 to 0), 3 (Visit 4, Week 12, 6 (Visit 7, Week 24), and 12 months (Visit 14, 52 weeks ±14 days).
4. Safety - The proportion of patients who develop progressive disease during the trial at 6 and 12 months. Progression is defined in section 3.4.
5. Progression to surgery - The proportion of patients who progress to surgical management of endometrial cancer ie. hysterectomy following weight loss

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University College Dublin

Sponsor organisation

University College Dublin

Address

Catherine Mcauley Centre, 21 Nelson Street, Phibsborough 21 Nelson Street Phibsborough

City

Dublin 7

Postcode

DUB LIN7

Country

Ireland

Scientific contact point

Organisation

University College Dublin

Contact name

prof. Donal Brennan

Public contact point

Organisation

University College Dublin

Contact name

Aleksandra Sadlocha

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications