Uterine CancerPREFACENCT06799624
Prognostic Role of molEcular classiFication in Fertility-sparing treAtment of Endometrial canCEr
An observational study of Uterine Cancer, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
Trial summary
Endometrial cancer, the most common gynecologic malignancy in high-income countries, is increasing among reproductive-age women. While hysterectomy prevents pregnancy, hormonal therapies offer fertility-sparing options for select early-stage cases, with ~80% achieving complete response (CR). Read more about this study
- Who is it for?
- Ages 18 to 50 years, women only
- Conditions the study is for
- Uterine Cancer
- What is being tested?
- Observation only
- How many people
- 100 participants
- Where
- 1 siteItaly
- Study dates
- 1 Jan 2026to 31 Jan 2028
- Phase
- Observational
- 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 50 years
- Women only
- No healthy volunteers
- Adult
Study population: This is a prospective study enrolling patients with endometrial cancer eligible for fertility-sparing treatment. Data of consecutive patients treated from the 21st of January 2025.
Who may be able to join
- Patients aged 18-45 years with a hysteroscopic confirmed diagnosis of endometrial cancer (FIGO stage IA without myometrial invasion, grade 1 or grade 2, endometrioid histology).
- Patients desiring fertility preservation
- Molecular classification of the tumor using next-generation sequencing (NGS) or Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE).
- Adequate pre-treatment imaging (MRI or transvaginal ultrasound) confirming no evidence of myometrial invasion or extrauterine spread.
Who cannot join
- Patients with atypical endometrial hyperplasia or intraepithelial neoplasia
- Individuals with tumor samples of insufficient quantity or inadequate quality were not included in the analysis
- Non-endometrioid histology.
- Patients with a history of prior uterine malignancy or current synchronous malignancies.
- Medical contraindications to hormonal therapy
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
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
Milan, Michigan, 20133
About this study
Official title: Prognostic Role of molEcular classiFication in Fertility-sparing treAtment of Endometrial canCEr: PREFACE Study
Endometrial cancer, the most common gynecologic malignancy in high-income countries, is increasing among reproductive-age women. While hysterectomy prevents pregnancy, hormonal therapies offer fertility-sparing options for select early-stage cases, with ~80% achieving complete response (CR). Molecular classifications (POLEmut, p53abn, MMRd/MSI-H, NSMP) reveal subtype-specific prognostic differences, with NSMP showing higher CR rates and lower recurrence, while p53abn and MMRd/MSI-H fare worse. Recent studies emphasize molecular profiling's potential to guide personalized fertility-sparing treatments. This study explores the prognostic role of these classifications in treatment outcomes.
Read the detailed description
Endometrial cancer is the most common gynecologic malignancy in high-income countries, with an increasing incidence among women of reproductive age. In 2024, over 65,000 new cases were diagnosed in the United States alone. The prevalence of endometrial cancer in younger women who desire to preserve their fertility presents a significant clinical challenge. Traditional treatment for endometrial cancer involves hysterectomy, which precludes future pregnancies. However, fertility-sparing treatments, primarily using hormonal therapies, have emerged as a viable option for select patients with low-grade, early-stage endometrial cancer. Despite reported complete response (CR) rates of approximately 80% with fertility-sparing therapy, the outcomes vary significantly among patients. Molecular classifications have revolutionized the understanding of endometrial cancer by identifying four distinct subtypes: POLEmut (ultramutated), p53abn (TP53-mutant), MMRd/MSI-H (mismatch repair deficiency/microsatellite instability-high), and NSMP (no specific molecular profile). These classifications have demonstrated prognostic value in predicting oncologic outcomes in endometrial cancer. For instance, the NSMP subtype is associated with higher CR rates (78.4%) and lower recurrence rates (18.4%), whereas MMRd/MSI-H and p53abn subtypes show significantly poorer outcomes, including lower CR rates (48.8% and 50%, respectively) and higher recurrence rates (42.8% and 33%). However, the role of these molecular subtypes in guiding fertility-sparing treatment remains underexplored.
A recent meta-analysis synthesized data from eight studies involving 363 patients who underwent fertility-sparing treatment for endometrial cancer. This analysis highlighted significant differences in complete response to treatment and in oncologic outcomes among the molecular subtypes, emphasizing the potential utility of molecular classification in personalizing treatment strategies. This study aims to build on these findings by prospectively evaluating the prognostic role of molecular classifications in a well-defined cohort of endometrial cancer patients undergoing fertility-sparing treatment.
- Conditions
- Uterine Cancer
- Being tested
- Observation only
- Keywords
- uterine cancer, fertility-sparing, molecular classification
- Medical subject headings
- Uterine Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Observation onlyOther
Only observation following standard of care (histological diagnosis, molecular classification, progestine therapy)
| Study group | Role | What they receive |
|---|---|---|
| Patients with endometrial cancer eligible for fertility-sparing treatment | Patients diagnosed with endometrial cancer who meet the criteria for inclusion in a fertility-sparing treatment pathway and for whom molecular classification data is available. Receives: Other: Observation only |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response to fertility sparing treatmetn
To assess the differences in Complete Response (CR), Partial response/stable disease (PR/SD) and progression disease (PD) rates among molecular subtypes (NSMP, POLEmut, p53abn, MMRd/MSI-H) of endometrial cancer in patients undergoing fertility-sparing treatment.
Measured: 12 months
Recurrence
To evaluate the recurrence rates of endometrial cancer among these molecular subtypes following fertility-sparing treatment after a CR
Measured: 12 months
Secondary outcomes (2)
Time to CR response
The number of months elapsed from the start of therapy to achieving a complete response.
Measured: 12 months
Obstetric outcomes
After fertility-sparing treatment, we assess outcomes such as pregnancy rate (percentage of individuals achieving pregnancy) and live birth rate (percentage of pregnancies resulting in a live baby) for the cohort.
Measured: 12 mesi
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2025
- Study start1 Jan 2026 (estimated)
- Primary completion31 Jan 2028 (estimated)
- Study completion31 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Uterine CancerStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06799624
- Sponsor's protocol ID
- int
- Acronym
- PREFACE
- Status last verified
- Jan 2025
- First submitted
- 23 Jan 2025
- Last updated
- 23 Dec 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 23 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prognostic Role of molEcular classiFication in Fertility-sparing treAtment of Endometrial canCEr: PREFACE Study
- ClinicalTrials.gov ID
- NCT06799624
- Acronym / sponsor ID
- PREFACE / int
- Conditions
- Uterine Cancer
- Keywords
- uterine cancer, fertility-sparing, molecular classification
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoUniversity, hospital or other
- Study start
- 1 Jan 2026 (estimated)
- Primary completion
- 31 Jan 2028 (estimated)
- Study completion
- 31 Jan 2028 (estimated)
- First posted
- 29 Jan 2025 (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 cancer, the most common gynecologic malignancy in high-income countries, is increasing among reproductive-age women. While hysterectomy prevents pregnancy, hormonal therapies offer fertility-sparing options for select early-stage cases, with ~80% achieving complete response (CR). Molecular classifications (POLEmut, p53abn, MMRd/MSI-H, NSMP) reveal subtype-specific prognostic differences, with NSMP showing higher CR rates and lower recurrence, while p53abn and MMRd/MSI-H fare worse. Recent studies emphasize molecular profiling's potential to guide personalized fertility-sparing treatments. This study explores the prognostic role of these classifications in treatment outcomes.
Detailed description
Endometrial cancer is the most common gynecologic malignancy in high-income countries, with an increasing incidence among women of reproductive age. In 2024, over 65,000 new cases were diagnosed in the United States alone. The prevalence of endometrial cancer in younger women who desire to preserve their fertility presents a significant clinical challenge. Traditional treatment for endometrial cancer involves hysterectomy, which precludes future pregnancies. However, fertility-sparing treatments, primarily using hormonal therapies, have emerged as a viable option for select patients with low-grade, early-stage endometrial cancer. Despite reported complete response (CR) rates of approximately 80% with fertility-sparing therapy, the outcomes vary significantly among patients. Molecular classifications have revolutionized the understanding of endometrial cancer by identifying four distinct subtypes: POLEmut (ultramutated), p53abn (TP53-mutant), MMRd/MSI-H (mismatch repair deficiency/microsatellite instability-high), and NSMP (no specific molecular profile). These classifications have demonstrated prognostic value in predicting oncologic outcomes in endometrial cancer. For instance, the NSMP subtype is associated with higher CR rates (78.4%) and lower recurrence rates (18.4%), whereas MMRd/MSI-H and p53abn subtypes show significantly poorer outcomes, including lower CR rates (48.8% and 50%, respectively) and higher recurrence rates (42.8% and 33%). However, the role of these molecular subtypes in guiding fertility-sparing treatment remains underexplored.
A recent meta-analysis synthesized data from eight studies involving 363 patients who underwent fertility-sparing treatment for endometrial cancer. This analysis highlighted significant differences in complete response to treatment and in oncologic outcomes among the molecular subtypes, emphasizing the potential utility of molecular classification in personalizing treatment strategies. This study aims to build on these findings by prospectively evaluating the prognostic role of molecular classifications in a well-defined cohort of endometrial cancer patients undergoing fertility-sparing treatment.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with endometrial cancer eligible for fertility-sparing treatment | – | Other: Observation onlyPatients diagnosed with endometrial cancer who meet the criteria for inclusion in a fertility-sparing treatment pathway and for whom molecular classification data is available. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- This is a prospective study enrolling patients with endometrial cancer eligible for fertility-sparing treatment. Data of consecutive patients treated from the 21st of January 2025.
Key inclusion criteria (4 listed)
- Patients aged 18-45 years with a hysteroscopic confirmed diagnosis of endometrial cancer (FIGO stage IA without myometrial invasion, grade 1 or grade 2, endometrioid histology).
- Patients desiring fertility preservation
- Molecular classification of the tumor using next-generation sequencing (NGS) or Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE).
- Adequate pre-treatment imaging (MRI or transvaginal ultrasound) confirming no evidence of myometrial invasion or extrauterine spread.
Key exclusion criteria (5 listed)
- Patients with atypical endometrial hyperplasia or intraepithelial neoplasia
- Individuals with tumor samples of insufficient quantity or inadequate quality were not included in the analysis
- Non-endometrioid histology.
- Patients with a history of prior uterine malignancy or current synchronous malignancies.
- Medical contraindications to hormonal therapy
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 |
|---|---|---|
| Observation onlyOnly observation following standard of care (histological diagnosis, molecular classification, progestine therapy) | Other | Patients with endometrial cancer eligible for fertility-sparing treatment |
Primary outcome
Response to fertility sparing treatmetn
Time frame: 12 months
To assess the differences in Complete Response (CR), Partial response/stable disease (PR/SD) and progression disease (PD) rates among molecular subtypes (NSMP, POLEmut, p53abn, MMRd/MSI-H) of endometrial cancer in patients undergoing fertility-sparing treatment.
Recurrence
Time frame: 12 months
To evaluate the recurrence rates of endometrial cancer among these molecular subtypes following fertility-sparing treatment after a CR
2 secondary outcomes
Time to CR response
Time frame: 12 months
Obstetric outcomes
Time frame: 12 mesi
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 23 Dec 2025.
- Individual participant dataSharing planned: Undecided
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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?
An observational study of Uterine Cancer, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano 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 4 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 23 Dec 2025. 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 Filippo Ferrari, MD (3803933116, filippo.ferrari@istitutotumori.mi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response to fertility sparing treatmetn (time frame: 12 months). The study lists 2 primary outcomes in all. 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 23 Dec 2025; AzTrials last refreshed its copy on 8 Nov 2026.