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NCT Number: NCT06935344

Evaluation of Polygenic Risk Score for Epithelial OVarian cancEr Risk Prediction: the PROVE Study

The goal of this observational study is to evaluate whether polygenic risk score (PRS) assessment can help predict the onset of epithelial ovarian cancer in women aged over 18, comparing those with a histologically confirmed diagnosis of epithelial ovarian or fallopian tube cancer (cases) to women with no personal history of ovarian cancer (controls). The main questions it aims to answer are:

* Is there an association between PRS and the presence of epithelial ovarian cancer? * Can PRS improve the prediction of ovarian cancer risk when adjusted for other clinical factors?

Researchers will compare PRS values between cases and controls to see if higher PRS percentiles are associated with an increased risk of ovarian cancer.

Participants will:

* Complete a questionnaire on socio-economic status, lifestyle, and dietary habits. * Undergo blood sampling, for the analysis of BRCA1-2, PALB2, RAD51C, RAD51D pathogenic variants. * Undergo PRS analysis.

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Key information

Conditions

Ovarian Cancer Adnexal Diseases Disease Attributes Disease Susceptibility Endocrine Gland Neoplasms Endocrine System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genetic Predisposition to Disease Genetic Risk Score Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Gonadal Disorders Neoplasms Neoplasms by Site Ovarian Diseases Ovarian Neoplasms Pathologic Processes Pathological Conditions, Signs and Symptoms Urogenital Diseases Urogenital Neoplasms

Age range

18 year and older

Sex eligibility

Female

Study type

Observational

Primary location

Dipartimento Universitario di Scienze della Vita e Sanità Pubblica

Roma, Italia, 00168, Italy

Location status: Recruiting

Location contact

Stefania Boccia

CONTACT

[email protected]

0630154396

About this study

This study aims to investigate epithelial ovarian cancer (EOC) through a combined case-control and prospective cohort design, focusing on genetic, clinical, and lifestyle risk factors.

The recruitment phase will last 12 months, conducted at Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome. Cases will include women with histologically confirmed EOC, while controls will be women without a history of ovarian cancer, consecutively recruited from the Rheumatology Unit. Eligible participants must be ≥18 years old and provide informed consent. Women with concurrent malignancies other than OC will be excluded.

Study Procedures Baseline Visit

After signing informed consent, participants will undergo the following assessments:

  • Structured Questionnaire: Collection of socio-demographic data, medical and family history, obstetric history, lifestyle factors, comorbidities, and potential ovarian cancer risk factors.
  • Blood Sampling: Blood will be collected for molecular analysis, including BRCA1/2 mutational status and Polygenic Risk Score (PRS) evaluation. PRS results will be available to participants upon request, while pathogenic BRCA results will be referred to a geneticist and managed according to clinical practice.

A fertility-sparing approach will be considered for patients of reproductive age who express a desire for future fertility and are diagnosed with FIGO stage IA or IC1 ovarian cancer of low-grade serous, grade 1-2 endometrioid, or expansile mucinous histology. Tissue samples obtained from macroscopically normal ovarian tissue in patients undergoing fertility-sparing surgery (cases) will be analyzed ex vivo using Full-Field Optical Coherence Tomography and Dynamic Cell Imaging.

For the pharmagenetics analysis, patients will be divided into different groups based on the treatment type received (i.e. PARPi, chemo, moAB) and each drug will be characterised by different groups of pharmacogenetic profiles involved in their efficacy and toxicity. The pharmacogenetic signature will also be evaluated to determine the drug-drug interaction risks in patients undergoing multiple treatments for comorbidities.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • For cases: women with a first-time diagnosis of histologically confirmed epithelial ovarian or fallopian tube cancer.
  • For Controls women with no concomitant or past OC diagnosis.

Exclusion criteria

  • For both cases and controls: the presence of concurrent malignancies other from OC.

Treatment and study plan

Polygenic Risk Score

Genetic

For the PRS analysis, SNPs for genotyping will be selected based on the latest findings from GWAS on EOC, particularly leveraging the results, as reported by Dareng et al. (doi:10.1038/s41431-021-00987-7). The PRS will be calculated as a weighted sum of risk alleles based on the selected SNPs.

Biopsy on normal contralateral ovary

Diagnostic Test

During fertility-sparing surgery for early-stage ovarian cancer, tissue samples will be obtained from macroscopically normal ovarian tissue and analyzed ex vivo using Full-Field Optical Coherence Tomography (FF-OCT) combined with Dynamic Cell Imaging (DCI). The analysis will be performed with the VanGogh biopsy system (AQUYRE Biosciences).

Pharmacogenetic profiles

Genetic

Identifying distinct pharmacogenetic profiles associated with different responses and toxicities from standard treatments. Patients will be divided into different groups based on the treatment type received (i.e. PARPi, chemo, moAB) and each drug will be characterised by different groups of pharmacogenetic profiles involved in their efficacy and toxicity.

The genetic fingerprints involved in the absorption, distribution, metabolism and elimination of administered drugs will be evaluated to retrospectively correlate the efficacy and the safety profile of therapies and the expected enzymatic activity of patients.

Full-Field Optical Coherence Tomography (FF-OCT), combined with Dynamic Cell Imaging (Van Gogh System) on detecting ovarian cancer lesions from tissue samples

Diagnostic Test

Tissue samples retrieved during surgery in eligible patients will be analyzed ex vivo using Full-Field Optical Coherence Tomography and Dynamic Cell Imaging. Samples will be assessed without any alteration, damage, or need for fixation, and this procedure will not interfere with the standard diagnostic workflow.

Other names: biopsy

Primary outcomes

  1. Odds of developing EOC by different PRS percentiles

    Time frame: At enrollment

    Correlation between PRS percentiles and EOC risk

Secondary outcomes

  1. Correlation of PRS percentiles and covariates

    Time frame: At enrollment

    Correlation between PRS percentiles and: age, familiarity with OC, stage, histotype, grading (1-2 versus 3), BRCA1-2, PALB2, RAD51C, RAD51D, FANCM status, type of surgery, residual tumor (RT) at histology, type of chemotherapy, maintenance, chemo-resistance, response to treatment, recurrences, progressions, cancer-specific deaths, Disease Free survival (DFS) hazard ratio (HR), Overall Survival (OS) HR.

  2. Diagnostic accuracy of Full-Field Optical Coherence Tomography (FF-OCT), combined with Dynamic Cell Imaging (Van Gogh System)

    Time frame: At enrollment

    The diagnostic accuracy will be assessed by estimating sensitivity, specificity, accuracy, and predictive values against the histopathological gold standard. These statistics will be derived from 2×2 contingency tables and presented with two-sided 95% CIs.

  3. Frequency of functional genotypes in drug-metabolizing enzymes and transporters

    Time frame: At enrollment

    Number of genes associated with treatment response identified

Study contacts

Contact information is provided by the study sponsor or research team.

Stefania Boccia

CONTACT

[email protected]

+39 0630154396

Sponsors and collaborators

Lead sponsor

Catholic University of the Sacred Heart

Other

Collaborators

  • Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Registry information

Official study title

Evaluation of Polygenic Risk Score for Epithelial OVarian cancEr Risk Prediction and Clinical Outcomes in an Italian Population: the PROVE Study

Acronym: PROVE

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Apr 20, 2025
Registry last updated
Mar 3, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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