High Grade Serous Ovarian CancerFRONTIERNCT07889843
Folate Receptor Alpha (FRα) Expression and Heterogeneity in Epithelial Ovarian Cancer
An observational study of High Grade Serous Ovarian Cancer and Folate Receptor Alpha Positive, run by Hellenic Cooperative Oncology Group at 1 site in Greece.
Trial summary
This is a single-country, retrospective, observational biomarker study conducted in Greece to evaluate Folate Receptor Alpha (FRα) expression in patients with high-grade serous ovarian, fallopian tube, and primary peritoneal cancer at the time of diagnosis. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- High Grade Serous Ovarian Cancer, Folate Receptor Alpha Positive
- How many people
- 200 participants
- Where
- 1 siteGreece
- Study dates
- 10 Jul 2026to 30 Apr 2027
- Phase
- Observational
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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: The study population will consist of approximately 200 female patients aged ≥18 years with histologically confirmed high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer. Tumor tissue samples will be retrospectively collected from the HeCOG biobank and affiliated clinical sites between January 1, 2001 and July 30, 2025. Only samples with adequate tissue quality for immunohistochemical analysis will be included. Cases with non-epithelial ovarian tumors or non-high-grade serous histologies (e.g., endometrioid, mucinous, or clear cell carcinoma) will be excluded.
Who may be able to join
- Female patients.
- 18 years of age or older.
- Patients diagnosed with high-grade serous epithelial ovarian cancer according to pathologists' report.
Who cannot join
- Diagnosis of non-epithelial ovarian tumors
- Diagnosis of endometrioid, mucinous, or clear cell carcinomas.
- Inadequate (poor quality or inadequate posology for analysis) tissue samples.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Maria Moschoni contact
Greece1 site, 1 recruiting
- Recruiting
Hellenic Cooperative Oncology Group
Athens
Hellenic Cooperative Oncology Group Hellenic Cooperative Oncology Group, +302106912520, hecogoff@otenet.gr
elenafou@gmail.com
About this study
This is a single-country, retrospective, observational biomarker study conducted in Greece to evaluate Folate Receptor Alpha (FRα) expression in patients with high-grade serous ovarian, fallopian tube, and primary peritoneal cancer at the time of diagnosis. Approximately 200 eligible female patients (≥18 years) diagnosed between 1 January 2001 and 30 July 2025 will be included from around 15 clinical sites affiliated with the Hellenic Cooperative Oncology Group.
Historically collected Formalin-Fixed Paraffin-Embedded (FFPE) tissue samples stored in the Hellenic Cooperative Oncology Group biobank will be analyzed centrally using the Ventana FOLR1 RxDx assay to determine FRα expression. Only samples collected at initial diagnosis will be included; relapse samples will be excluded.
Read more
The primary objective is to assess the prevalence of FRα-positive status, defined as ≥75% viable tumor cells with moderate (2+) and/or strong (3+) membrane staining. Secondary objectives include evaluation of intra-tumoral heterogeneity, concordance between primary and metastatic lesions, prevalence of lower FRα expression levels, and associations between FRα expression and clinical characteristics, BRCA/HRD status, progression-free survival (PFS), and overall survival (OS).
All analyses will be descriptive, with additional exploratory statistical methods including chi-square tests, Cohen's kappa, correlation analyses, ANOVA, Kaplan-Meier survival analysis, and Cox proportional hazards models. Data will be retrospectively collected from the Hellenic Cooperative Oncology Group registry and medical records and entered into a secure REDCap eCRF system.
- Keywords
- ovarian cancer, biomarker
- Medical subject headings
- Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients with High-Grade Serous Ovarian, Fallopian Tube, and Primary Peritoneal Cancer | This cohort includes approximately 200 eligible female patients aged 18 years or older diagnosed with high-grade serous ovarian, fallopian tube, or primary peritoneal cancer between 1 January 2001 and 30 July 2025. Patients are identified retrospectively from approximately 15 clinical sites in Greece affiliated with the Hellenic Cooperative Oncology Group. Historically collected Formalin-Fixed Paraffin-Embedded (FFPE) tissue samples obtained at the time of initial diagnosis and stored in the Hellenic Cooperative Oncology Group biobank will be analyzed centrally using the Ventana FOLR1 RxDx assay to determine Folate Receptor Alpha (FRα) expression. |
What is being measured
The primary outcome is the main question the study is designed to answer.
FRα-Positive Status
Assessment of FRα-positive status at diagnosis, defined as ≥75% of viable tumor cells demonstrating moderate (2+) and/or strong (3+) membrane staining by immunohistochemistry.
Measured: Baseline
Secondary outcomes (5)
FRα expression
Qualitative assessment of FRα expression in tumor samples at diagnosis based on immunohistochemical staining intensity (2+ and 3+) and distribution across viable tumor cells.
Measured: Baseline
FRα expression levels
Assessment of FRα expression levels categorized according to the percentage of viable tumor cells showing moderate (2+) and/or strong (3+) membrane staining, grouped into predefined categories (0-24%, 25-49%, 50-74%, and ≥75%).
Measured: Baseline
FRα expression levels and PFS/OS
Evaluation of the association between FRα expression levels (0-24%, 25-49%, 50-74%, ≥75%) and clinical outcomes, including progression-free survival (PFS) and overall survival (OS).
Measured: From initiation of first-line treatment until disease progression, death, or last follow-up, whichever occurs first (for PFS); and until death from any cause or last follow-up (for OS), assessed up to 120 months
FRα expression score
Quantitative assessment of FRα expression as a continuous variable, defined as the percentage of viable tumor cells demonstrating moderate (2+) and/or strong (3+) membrane staining.
Measured: Baseline
FRα expression score and BRCA/HRD status
Assessment of the association between FRα expression score and tumor molecular status, including BRCA mutation status and homologous recombination deficiency (HRD), in samples obtained at diagnosis.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2026
- Study start10 Jul 2026
- Primary completion30 Dec 2026 (estimated)
- Study completion30 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for High Grade Serous Ovarian CancerStudies of the same condition, open and under way.
- 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
- Retrospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hellenic Cooperative Oncology Group
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07889843
- Sponsor's protocol ID
- ΗΕ_4FR/26
- Acronym
- FRONTIER
- Status last verified
- Apr 2026
- First submitted
- 21 Jul 2026
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Zannoni GF, Santoro A, d'Amati A, D'Alessandris N, Scaglione G, Padial Urtueta B, Valente M, Narducci N, Addante F, Spadola S, Bragantini E, Angelico G. Folate Receptor Alpha in Advanced Epithelial Ovarian Cancer: Diagnostic Role and Therapeutic Implications of a Clinically Validated Biomarker. Int J Mol Sci. 2025 May 29;26(11):5222. doi: 10.3390/ijms26115222.
PubMed 40508029Previs RA, Strickland KC, Wallen Z, Ko H, Green M, Cooper M, Lyon E, Biorn M, Armetta J, Quarles R, Watson CH, Ring K, Klein JL, Caveney B, Severson EA, Ramkissoon S. Analysis of real world FRalpha testing in ovarian, fallopian tube, and primary peritoneal cancers. Gynecol Oncol. 2025 Jan;192:102-110. doi: 10.1016/j.ygyno.2024.11.010. Epub 2024 Dec 3.
PubMed 39631181Moore KN, Angelergues A, Konecny GE, Garcia Y, Banerjee S, Lorusso D, Lee JY, Moroney JW, Colombo N, Roszak A, Tromp J, Myers T, Lee JW, Beiner M, Cosgrove CM, Cibula D, Martin LP, Sabatier R, Buscema J, Estevez-Garcia P, Coffman L, Nicum S, Duska LR, Pignata S, Galvez F, Wang Y, Method M, Berkenblit A, Bello Roufai D, Van Gorp T; Gynecologic Oncology Group Partners and the European Network of Gynaecological Oncological Trial Groups. Mirvetuximab Soravtansine in FRalpha-Positive, Platinum-Resistant Ovarian Cancer. N Engl J Med. 2023 Dec 7;389(23):2162-2174. doi: 10.1056/NEJMoa2309169.
PubMed 38055253Matulonis UA, Lorusso D, Oaknin A, Pignata S, Dean A, Denys H, Colombo N, Van Gorp T, Konner JA, Marin MR, Harter P, Murphy CG, Wang J, Noble E, Esteves B, Method M, Coleman RL. Efficacy and Safety of Mirvetuximab Soravtansine in Patients With Platinum-Resistant Ovarian Cancer With High Folate Receptor Alpha Expression: Results From the SORAYA Study. J Clin Oncol. 2023 May 1;41(13):2436-2445. doi: 10.1200/JCO.22.01900. Epub 2023 Jan 30.
PubMed 36716407Martin LP, Konner JA, Moore KN, Seward SM, Matulonis UA, Perez RP, Su Y, Berkenblit A, Ruiz-Soto R, Birrer MJ. Characterization of folate receptor alpha (FRalpha) expression in archival tumor and biopsy samples from relapsed epithelial ovarian cancer patients: A phase I expansion study of the FRalpha-targeting antibody-drug conjugate mirvetuximab soravtansine. Gynecol Oncol. 2017 Nov;147(2):402-407. doi: 10.1016/j.ygyno.2017.08.015. Epub 2017 Aug 24.
PubMed 28843653Kalli KR, Oberg AL, Keeney GL, Christianson TJ, Low PS, Knutson KL, Hartmann LC. Folate receptor alpha as a tumor target in epithelial ovarian cancer. Gynecol Oncol. 2008 Mar;108(3):619-26. doi: 10.1016/j.ygyno.2007.11.020. Epub 2008 Jan 28.
PubMed 18222534Gonzalez T, Muminovic M, Nano O, Vulfovich M. Folate Receptor Alpha-A Novel Approach to Cancer Therapy. Int J Mol Sci. 2024 Jan 15;25(2):1046. doi: 10.3390/ijms25021046.
PubMed 38256120Bax HJ, Chauhan J, Stavraka C, Santaolalla A, Osborn G, Khiabany A, Grandits M, Lopez-Abente J, Palhares LCGF, Chan Wah Hak C, Robinson A, Pope A, Woodman N, Naceur-Lombardelli C, Malas S, Coumbe JEM, Nakamura M, Laddach R, Mele S, Crescioli S, Black AM, Lombardi S, Canevari S, Figini M, Sayasneh A, Tsoka S, FitzGerald K, Gillett C, Pinder S, Van Hemelrijck M, Kristeleit R, Ghosh S, Montes A, Spicer J, Karagiannis SN, Josephs DH. Folate receptor alpha in ovarian cancer tissue and patient serum is associated with disease burden and treatment outcomes. Br J Cancer. 2023 Jan;128(2):342-353. doi: 10.1038/s41416-022-02031-x. Epub 2022 Nov 19.
PubMed 36402875Ali AT, Al-Ani O, Al-Ani F. Epidemiology and risk factors for ovarian cancer. Prz Menopauzalny. 2023 Jun;22(2):93-104. doi: 10.5114/pm.2023.128661. Epub 2023 Jun 14.
PubMed 37674925