Longitudinal Plasma Proteomic Remodeling in Ovarian Cancer

NCT07684846 | Completed

• 1 other identifier: KOG UMC LJUBLJANA
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This longitudinal observational study investigates treatment-associated changes in the circulating plasma proteome of patients with ovarian cancer undergoing standard treatment. Although CA125 and HE4 are established biomarkers for monitoring treatment response, they provide only a limited view of the complex biological processes occurring during therapy. The study includes patients with epithelial ovarian cancer and primary peritoneal Müllerian tumors who underwent surgery and/or platinum-based chemotherapy. Plasma samples were collected at three predefined treatment timepoints: before surgery (T1), after surgery (T2), and after completion of chemotherapy (T3). A panel of 92 circulating proteins was quantified using Olink proximity extension assay technology. Longitudinal proteomic changes were evaluated in relation to established clinical biomarkers (CA125 and HE4), exploratory proliferation-associated biomarker thymidine kinase 1 (TK1), and KELIM-defined chemosensitivity. The primary objective is to characterize treatment-associated remodeling of the circulating proteome and determine whether these molecular changes reflect tumor burden reduction, treatment exposure, or chemotherapy sensitivity. Secondary objectives include identification of proteins and biological pathways associated with treatment timepoints and assessment of concordance between proteomic changes and established clinical biomarkers. This study aims to improve understanding of dynamic tumor-host interactions during ovarian cancer treatment and to explore the potential role of longitudinal proteomic profiling as a complement to conventional biomarker monitoring.

Conditions

Ovarian Cancer; Ovarian Cancer Recurrent

Outcome Measures

Primary Outcomes (1)

• Treatment-associated changes in circulating plasma protein levels

  Identification of circulating proteins significantly associated with treatment timepoint (pre-operative, post-operative, and post-chemotherapy) as measured by Olink normalized protein expression (NPX) values and analyzed using longitudinal mixed-effects models.

  Time 1 (Baseline, prior to primary cytoreductive surgery); Time 2 (1 month after primary cytoreductive surgery); Time 3 (after completion of first-line chemotherapy, up to 12 months after treatment initiation).

Secondary Outcomes (1)

• Changes in serum CA125 and HE4 concentrations across treatment timepoints and their association with longitudinal proteomic remodeling.

  Time 1 (Baseline, prior to surgery); Time 2 (1 month after primary cytoreductive surgery); Time 3 (after completion of first-line chemotherapy, up to 12 months after treatment initiation).

Study Arms (1)

Standard-of-Care Ovarian Cancer Treatment

EXPERIMENTAL

Patients with epithelial ovarian cancer or primary peritoneal Müllerian tumors undergoing standard clinical management, including primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery, platinum-based chemotherapy, and maintenance therapy when clinically indicated. Serial plasma samples were collected for longitudinal proteomic analysis.

Other: Longitudinal Plasma Biomarker Assessment

Interventions

Longitudinal Plasma Biomarker Assessment OTHER

Serial plasma sampling and proteomic profiling using Olink proximity extension assay technology performed at predefined treatment timepoints (pre-operative, post-operative, and post-chemotherapy). Clinical biomarkers including CA125, HE4, thymidine kinase 1 (TK1), and KELIM-defined chemosensitivity were analyzed in relation to longitudinal proteomic changes.

Standard-of-Care Ovarian Cancer Treatment

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years.
• Histologically confirmed epithelial ovarian cancer or primary peritoneal Müllerian carcinoma.
• Undergoing standard treatment including surgery and/or systemic therapy.
• Availability of plasma samples collected at one or more predefined treatment timepoints (pre-operative, post-operative, and/or post-chemotherapy).
• Availability of corresponding clinical and biomarker data (CA125 and/or HE4).
• Written informed consent

You may not qualify if:

• Non-epithelial ovarian malignancies.
• Insufficient plasma sample volume or inadequate sample quality for proteomic analysis.
• Missing essential clinical data required for study analyses.
• Withdrawal of informed consent.
• Concurrent participation in another study that would prevent interpretation of biomarker analyses.

Sponsors & Collaborators

• Helmholtz Zentrum München: collaborator
• University Medical Centre Ljubljana: lead

Study Sites (1)

UMC Ljubljana

Ljubljana, Slovenia

Location

Related Publications (1)

• [1] Konstantinopoulos PA, Matulonis UA. Clinical and translational advances in ovarian cancer therapy. Nat Cancer. 2023 Sep;4(9):1239-1257. doi: 10.1038/s43018-023-00617-9. [2] Whitwell HJ, Worthington J, Blyuss O, Gentry-Maharaj A, Ryan A, Gunu R et al. Improved early detection of ovarian cancer using longitudinal multimarker models. Br J Cancer. 2020 Mar;122(6):847-856. doi: 10.1038/s41416-019-0718-9. [3] Charkhchi P, Cybulski C, Gronwald J, Wong FO, Narod SA, Akbari MR. CA125 and Ovarian Cancer: A Comprehensive Review. Cancers (Basel). 2020 Dec 11;12(12):3730. doi: 10.3390/cancers12123730. [4] Alegría-Baños JA, Jiménez-López JC, Vergara-Castañeda A, de León DFC, Mohar-Betancourt A, Pérez-Montiel D et al. Kinetics of HE4 and CA125 as prognosis biomarkers during neoadjuvant chemotherapy in advanced epithelial ovarian cancer. J Ovarian Res. 2021 Jul 19;14(1):96. doi: 10.1186/s13048-021-00845-6. [5] You B, Colomban O, Heywood M, Lee C, Davy M, Reed N et al. The strong prognostic value of KELIM, a model-based parameter from CA 125 kinetics in ovarian cancer: data from CALYPSO trial (a GINECO-GCIG study). Gynecol Oncol. 2013 Aug;130(2):289-94. doi: 10.1016/j.ygyno.2013.05.013. [6] Lauby A, Colomban O, Corbaux P, Peron J, Van Wagensveld L, Gertych W et al. The Increasing Prognostic and Predictive Roles of the Tumor Primary Chemosensitivity Assessed by CA-125 Elimination Rate Constant K (KELIM) in Ovarian Cancer: A Narrative Review. Cancers (Basel). 2021 Dec 25;14(1):98. doi: 10.3390/cancers14010098. [7] Bradbury M, Borràs E, Pérez-Benavente A, Gil-Moreno A, Santamaria A, Sabidó E. Proteomic Studies on the Management of High-Grade Serous Ovarian Cancer Patients: A Mini-Review. Cancers (Basel). 2021 Apr 25;13(9):2067. doi: 10.3390/cancers13092067. [8] Qian L, Zhu J, Xue Z, et al. Proteomic landscape of epithelial ovarian cancer. Nat Commun. 2024;15(1):6462. doi: 10.1038/s41467-024-50786-z. [9] Li Y, Wang B, Yang W, Ma F, Zou J, Li K, Tan S, Feng J, Wang Y, Qin Z,

  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

Study Officials

• Joško Osredkar, Prof, PhD

  Institute of Clinical Chemistry and Biochemistry, Ljubljana University Medical Center

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2026
• First Posted: July 6, 2026
• Study Start: October 23, 2021
• Primary Completion: January 7, 2025
• Study Completion: March 10, 2025
• Last Updated: July 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

SL (1)