Endometrial Carcinoma (EC)DEMETERNCT07374809
IMMUNOTHERAPY EFFICACY TARGETING ENDOMETRIAL CANCER
A study testing DNA methylation profiles in people with Endometrial Carcinoma (EC) and pMMR, run by European Institute of Oncology at 1 site in Italy.
Trial summary
Endometrial carcinoma (EC) represents the most common gynecological malignancy in developed countries. Despite therapeutic advances, patients with advanced or recurrent disease still have a poor prognosis, with high recurrence rates and a 5-year survival of less than 20%. Read more about this study
- Who is it for?
- Ages 18 to 120 years, women only
- Conditions the study is for
- Endometrial Carcinoma (EC), pMMR, DMMR Cancer
- What is being tested?
- DNA methylation profiles
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteItaly
- Study dates
- 21 Jan 2026to 30 Nov 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female patients ≥ 18 years old.
- Histologically confirmed epithelial endometrial carcinoma (endometrioid, serous, clear cell, mixed, or carcinosarcoma).
- Advanced (stage III-IV) or recurrent disease, eligible for surgery or biopsy as part of the therapeutic plan.
- Availability of fresh-frozen or OCT-embedded tumor tissue obtained at surgery/biopsy and stored in the IEO Biobank.
- Mismatch-repair-deficient (dMMR) or -proficient (pMMR) molecular subtype (when available).
- Written informed consent for participation and use of biological material for translational research purposes.
Who cannot join
- Mesenchymal tumors or epithelial tumors of non-endometrial origin (e.g., ovarian, cervical).
- Prior systemic treatment with immune checkpoint inhibitors for other malignancies.
- Insufficient or poor-quality tumor tissue available for molecular analyses.
- Active or uncontrolled infection with HIV, HBV, or HCV.
- Any condition that, in the investigator's judgment, would compromise patient safety or study integrity.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site
Istituto Europeo di Oncologa
Milan, Lombardy, 20141
Ilaria Betella, MD, 00390257489431, ilaria.betella@ieo.it
About this study
Official title: DISSECTING THE EPIGENOME AND MICROENVIRONMENT TO UNDERSTAND IMMUNOTHERAPY EFFICACY TARGETING ENDOMETRIAL CANCER (DEMETER PROJECT)
Endometrial carcinoma (EC) represents the most common gynecological malignancy in developed countries. Despite therapeutic advances, patients with advanced or recurrent disease still have a poor prognosis, with high recurrence rates and a 5-year survival of less than 20%.
Recently, four phase III studies (RUBY, NRG-GY018, AtTEnd, and DUO-E) have demonstrated that the addition of anti-PD-1/PD-L1 immunotherapy to first-line chemotherapy significantly improves progression-free survival, particularly in tumors with altered DNA repair mechanisms known as mismatch repair (MMR) (so-called mismatch repair-deficient or dMMR tumors), but with benefits also observed in a subset of tumors with normal MMR function (so-called MMR-proficient or pMMR tumors). However, despite the clinical approval of these therapies, reliable biomarkers capable of predicting response to immunotherapy are still lacking.
This project aims to comprehensively characterize the genomic, epigenetic, and lipid properties of the tumor and the tumor microenvironment (TME) in order to identify predictive markers of response to immunotherapy, thereby laying the foundation for a personalized therapeutic approach in endometrial carcinoma.
Read the detailed description
Primary objective To identify and validate predictive biomarkers of response to immunotherapy in dMMR and pMMR endometrial carcinomas through an integrated multi-omics approach (genomic, epigenomic, transcriptomic, and lipidomic) and functional validation in patient-derived models.
Population characteristics Patients with advanced (stage III-IV) or recurrent epithelial endometrial carcinoma, treated with anti-PD-1/PD-L1 immunotherapy in combination with or following standard platinum-based chemotherapy at the European Institute of Oncology.
Inclusion criteria:
Advanced or recurrent endometrial carcinoma patients undergoing biopsy or cytoreductive surgery followed by immunotherapy
Age ≥ 18 years
Fresh tumor tissue available at the IEO Biobank
Written informed consent
Exclusion criteria:
Mesenchymal tumors
Carcinomas of non-endometrial origin
Chronic viral infections (HIV, HBV, HCV)
Number of patients and main criteria
- Total number of planned patients: 50
- Number of IEO patients: 50
- Competitive: No
- Special population: Rare disease / advanced tumor
- Sex and menopausal status: Female, pre- or post-menopausal
- Disease stage: III-IV (advanced or recurrent)
- Main subtypes: dMMR and pMMR; molecular subgroups (POLE, p53, NSMP) when available
Duration (in months)
- Enrollment duration: 18
- Follow-up duration: 12 (calculated from the last patient enrolled)
Rationale: with approximately 150 new EC cases per year at IEO (about 20% advanced/recurrent), enrolling 50 patients over 18 months is realistic; a 12-month follow-up allows for clinical evaluations (response/early PFS) that are useful for multi-omics analyses and validation.
- Conditions
- Endometrial Carcinoma (EC), pMMR, DMMR Cancer
- Being tested
- DNA methylation profiles
- Medical subject headings
- Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DNA methylation profilesDiagnostic test
MAP mutations, DNA methylation profiles, transcriptome, TME composition, and lipid abundance of tumor samples from EC patients that underwent immunotherapy;
| Study group | Role | What they receive |
|---|---|---|
| arm 1 | Experimental | Histologically confirmed epithelial endometrial carcinoma (endometrioid, serous, clear cell, mixed histology, or carcinosarcoma), classified as dMMR or pMMR -Availability of a fresh tumor sample suitable for study procedures Receives: Diagnostic Test: DNA methylation profiles |
What is being measured
The primary outcome is the main question the study is designed to answer.
predictive biomarkers
To identify and validate predictive biomarkers of response to immunotherapy in dMMR and pMMR endometrial carcinomas through an integrated multi-omics approach (genomic, epigenomic, transcriptomic, and lipidomic) and functional validation in patient-derived models.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2026
- Study start21 Jan 2026 (estimated)
- Primary completion30 Nov 2027 (estimated)
- Study completion30 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Endometrial Carcinoma (EC)Studies of the same condition, open and under way.
- More trials run by European Institute of OncologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- European Institute of Oncology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07374809
- Sponsor's protocol ID
- UID 5032
- Other IDs
- L2-516
- Acronym
- DEMETER
- Status last verified
- Dec 2025
- First submitted
- 21 Jan 2026
- Last updated
- 29 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- DISSECTING THE EPIGENOME AND MICROENVIRONMENT TO UNDERSTAND IMMUNOTHERAPY EFFICACY TARGETING ENDOMETRIAL CANCER (DEMETER PROJECT)
- ClinicalTrials.gov ID
- NCT07374809
- Acronym / sponsor ID
- DEMETER / UID 5032
- Conditions
- Endometrial Carcinoma (EC), pMMR, DMMR Cancer
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- European Institute of OncologyUniversity, hospital or other
- Study start
- 21 Jan 2026 (estimated)
- Primary completion
- 30 Nov 2027 (estimated)
- Study completion
- 30 Nov 2027 (estimated)
- First posted
- 29 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Endometrial carcinoma (EC) represents the most common gynecological malignancy in developed countries. Despite therapeutic advances, patients with advanced or recurrent disease still have a poor prognosis, with high recurrence rates and a 5-year survival of less than 20%.
Recently, four phase III studies (RUBY, NRG-GY018, AtTEnd, and DUO-E) have demonstrated that the addition of anti-PD-1/PD-L1 immunotherapy to first-line chemotherapy significantly improves progression-free survival, particularly in tumors with altered DNA repair mechanisms known as mismatch repair (MMR) (so-called mismatch repair-deficient or dMMR tumors), but with benefits also observed in a subset of tumors with normal MMR function (so-called MMR-proficient or pMMR tumors). However, despite the clinical approval of these therapies, reliable biomarkers capable of predicting response to immunotherapy are still lacking.
This project aims to comprehensively characterize the genomic, epigenetic, and lipid properties of the tumor and the tumor microenvironment (TME) in order to identify predictive markers of response to immunotherapy, thereby laying the foundation for a personalized therapeutic approach in endometrial carcinoma.
Detailed description
Primary objective To identify and validate predictive biomarkers of response to immunotherapy in dMMR and pMMR endometrial carcinomas through an integrated multi-omics approach (genomic, epigenomic, transcriptomic, and lipidomic) and functional validation in patient-derived models.
Population characteristics Patients with advanced (stage III-IV) or recurrent epithelial endometrial carcinoma, treated with anti-PD-1/PD-L1 immunotherapy in combination with or following standard platinum-based chemotherapy at the European Institute of Oncology.
Inclusion criteria:
Advanced or recurrent endometrial carcinoma patients undergoing biopsy or cytoreductive surgery followed by immunotherapy
Age ≥ 18 years
Fresh tumor tissue available at the IEO Biobank
Written informed consent
Exclusion criteria:
Mesenchymal tumors
Carcinomas of non-endometrial origin
Chronic viral infections (HIV, HBV, HCV)
Number of patients and main criteria
- Total number of planned patients: 50
- Number of IEO patients: 50
- Competitive: No
- Special population: Rare disease / advanced tumor
- Sex and menopausal status: Female, pre- or post-menopausal
- Disease stage: III-IV (advanced or recurrent)
- Main subtypes: dMMR and pMMR; molecular subgroups (POLE, p53, NSMP) when available
Duration (in months)
- Enrollment duration: 18
- Follow-up duration: 12 (calculated from the last patient enrolled)
Rationale: with approximately 150 new EC cases per year at IEO (about 20% advanced/recurrent), enrolling 50 patients over 18 months is realistic; a 12-month follow-up allows for clinical evaluations (response/early PFS) that are useful for multi-omics analyses and validation.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| arm 1 | Experimental | Diagnostic Test: DNA methylation profilesHistologically confirmed epithelial endometrial carcinoma (endometrioid, serous, clear cell, mixed histology, or carcinosarcoma), classified as dMMR or pMMR -Availability of a fresh tumor sample suitable for study procedures |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Female patients ≥ 18 years old.
- Histologically confirmed epithelial endometrial carcinoma (endometrioid, serous, clear cell, mixed, or carcinosarcoma).
- Advanced (stage III-IV) or recurrent disease, eligible for surgery or biopsy as part of the therapeutic plan.
- Availability of fresh-frozen or OCT-embedded tumor tissue obtained at surgery/biopsy and stored in the IEO Biobank.
- Mismatch-repair-deficient (dMMR) or -proficient (pMMR) molecular subtype (when available).
Key exclusion criteria (5 listed)
- Mesenchymal tumors or epithelial tumors of non-endometrial origin (e.g., ovarian, cervical).
- Prior systemic treatment with immune checkpoint inhibitors for other malignancies.
- Insufficient or poor-quality tumor tissue available for molecular analyses.
- Active or uncontrolled infection with HIV, HBV, or HCV.
- Any condition that, in the investigator's judgment, would compromise patient safety or study integrity.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DNA methylation profilesMAP mutations, DNA methylation profiles, transcriptome, TME composition, and lipid abundance of tumor samples from EC patients that underwent immunotherapy; | Diagnostic test | arm 1 |
Primary outcome
predictive biomarkers
Time frame: 2 years
To identify and validate predictive biomarkers of response to immunotherapy in dMMR and pMMR endometrial carcinomas through an integrated multi-omics approach (genomic, epigenomic, transcriptomic, and lipidomic) and functional validation in patient-derived models.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing DNA methylation profiles in people with Endometrial Carcinoma (EC) and pMMR, run by European Institute of Oncology at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 29 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ilaria Betella, MD, MD (00390257489431, ilaria.betella@ieo.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
predictive biomarkers (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2026.