Advancing Risk Stratification in Endometrial Cancer

NCT07746024 | Active Not Recruiting DMC

• 1 other identifier: 27614
• Study Type: observational
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

The DaPHNE study is an observational, ambispective, multicenter study designed to evaluate whether the integration of circulating tumor DNA (ctDNA) and plasma proteomic profiling with the 2023 FIGO staging system improves prognostic stratification in patients with endometrial cancer (EC) treated with curative-intent surgery. The study will compare the prognostic performance of the standard FIGO 2023 staging system with an enhanced longitudinal staging approach (L-FIGO 2023) incorporating preoperative (T0) and postoperative (T1, 4-6 weeks after surgery) liquid biopsy data, and will explore a dynamic model (Δ-FIGO) based on changes between these time points. The study consists of two phases: (1) a retrospective cohort including approximately 300 patients with stored plasma samples and clinical data, and (2) a prospective cohort of 100 newly enrolled patients from participating centers. Plasma samples will undergo ctDNA sequencing, methylation analysis, and proteomic profiling using next-generation sequencing and Olink technologies. Molecular findings will be integrated with clinicopathological and survival data to identify biomarkers associated with minimal residual disease, recurrence, and progression-free survival, validate multimodal prognostic models across institutions, assess concordance between circulating and tissue biomarkers, and identify molecular pathways relevant for personalized treatment strategies. The primary endpoint is progression-free survival.

Conditions

Endometrial Cancer

Keywords

endometrial cancer; liquid biopsy

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  Progression-free survival, defined as the time from curative-intent surgery to the first documented disease recurrence, progression, or death from any cause, comparing the prognostic performance of the FIGO 2023 staging system with the liquid biopsy-integrated L-FIGO 2023 staging model.

  Up to 36 months after surgery

Secondary Outcomes (2)

• Minimal residual disease (MRD) assessment

  4-6 weeks after surgery and during follow-up, up to 36 months

• Concordance between circulating biomarkers and tumor tissue molecular profiles

  Baseline and postoperative assessment, with analysis during the 36-month study period

Interventions

Liquid Biopsy DIAGNOSTIC_TEST

Collection and analysis of peripheral blood samples obtained before surgery (T0) and 4-6 weeks after surgery (T1) for circulating tumor DNA (ctDNA), DNA methylation, and plasma proteomic profiling.

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients affected by endometrial cancer (EC) who underwent radical surgery with no residual disease, with samples already collected in the Institutional Biobank (PHASE 1) or prospectively enrolled (PHASE 2).

You may qualify if:

• Women aged 18 or older
• Has a histologically confirmed new diagnosis of EC, regardless of histologic subtype or grade;
• EC staged according to the 2023 FIGO classification, with complete molecular assessment;
• Eligible for curative-intent debulking surgery with no residual disease at the end of surgery;
• No history of other malignancies within the preceding 3 years, except for curatively treated cervical carcinoma in situ, basal cell carcinoma of the skin, or ductal carcinoma in situ of the breast;
• For patients included in the prospective cohort, written informed consent will be obtained, whereas for those included in the retrospective cohort, reference will be made to Article 110-bis of the Italian Privacy Code

You may not qualify if:

• Has persistent, recurrent, or newly diagnosed metastatic EC that is not amenable to curative treatment;
• HIV, HBV or HCV-infected participants;
• Received prior systemic anticancer therapy;
• Patients with synchronous cancers.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Fondazione Policlinico Universitario Agostino Gemelli, IRCCS

Roma, 00186, Italy

Location

Related Publications (1)

• 1. Schwameis R, et al. Verification of the prognostic precision of the new 2023 FIGO staging system in endometrial cancer patients - An international pooled analysis of three ESGO accredited centres. PMID:37748967 2. Matsuo K, et al. Prognostic performance of the 2023 FIGO staging schema for endometrial cancer. PMID:38713997 3. Álvez MB, et al. Next generation pan-cancer blood proteome profiling using proximity extension assay. PMID:37463882 4. Capasso I, et al. Circulating tumor DNA in endometrial cancer: clinical significance and implications. PMID:39955181 5. Collins GS, et al. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement. PMID: 25562432 6. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009 Apr;42(2):377-81. doi: 10.1016/j.jbi.2008.08.010. Epub 2008 Sep 30. PMID: 18929686; PMCID: PMC2700030.

  RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood-derived plasma samples collected before surgery (T0) and 4-6 weeks after surgery (T1) will be retained for future analyses. Plasma samples will be used for circulating tumor DNA (ctDNA) extraction, targeted next-generation sequencing, DNA methylation profiling, and proteomic analyses. Associated clinical and molecular data generated from these samples may also be retained for future research related to endometrial cancer, in accordance with participants' informed consent and applicable regulations.

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

Liquid Biopsy

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Biopsy; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Investigative Techniques

Study Officials

• Camilla Nero

  Fondazione Policlinico Universitario Agostino Gemelli IRCCS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2026
• First Posted: August 4, 2026
• Study Start: July 23, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2029
• Last Updated: August 4, 2026

Record last verified: 2026-07

Locations

IT (1)