Folate Receptor Alpha (FRα) Expression and Heterogeneity in Epithelial Ovarian Cancer

NCT07889843 | Recruiting

• 1 other identifier: ΗΕ_4FR/26
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief 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. 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. 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.

Conditions

High Grade Serous Ovarian Cancer; Folate Receptor Alpha Positive

Keywords

ovarian cancer; biomarker

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline

Secondary Outcomes (5)

• FRα expression

  Baseline

• FRα expression levels

  Baseline

• FRα expression levels and PFS/OS

  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

  Baseline

• FRα expression score and BRCA/HRD status

  Baseline

Study Arms (1)

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.

Eligibility Criteria

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

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.

You may qualify if:

• Female patients.
• years of age or older.
• Patients diagnosed with high-grade serous epithelial ovarian cancer according to pathologists' report.

You may not qualify if:

• Diagnosis of non-epithelial ovarian tumors
• Diagnosis of endometrioid, mucinous, or clear cell carcinomas.
• Inadequate (poor quality or inadequate posology for analysis) tissue samples.

Sponsors & Collaborators

• Hellenic Cooperative Oncology Group: lead

Study Sites (1)

Hellenic Cooperative Oncology Group

Athens, Greece

RECRUITING

Related Publications (9)

• 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.

  PMID: 40508029 BACKGROUND

• Previs 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.

  PMID: 39631181 BACKGROUND

• Moore 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.

  PMID: 38055253 BACKGROUND

• Matulonis 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.

  PMID: 36716407 BACKGROUND

• Martin 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.

  PMID: 28843653 BACKGROUND

• Kalli 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.

  PMID: 18222534 BACKGROUND

• Gonzalez 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.

  PMID: 38256120 BACKGROUND

• Bax 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.

  PMID: 36402875 BACKGROUND

• Ali 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.

  PMID: 37674925 BACKGROUND

MeSH Terms

Conditions

Ovarian Neoplasms

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Central Study Contacts

Elena Fountzila

CONTACT

+306945779709; fountzila@oncogenome.gr

Maria Moschoni

CONTACT

+30 210 6912520

Study Design

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

Study Record Dates

• First Submitted: July 21, 2026
• First Posted: October 22, 2026
• Study Start: July 10, 2026
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): April 30, 2027
• Last Updated: October 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)