A Translational Study to Explore and Overcome Metabolic-driven Resistance Mechanisms to Standard Chemotherapy in High-grade Ovarian Cancer

This translational study, titled "A translational study to explore and overcome metabolic-driven resistance mechanisms to standard chemotherapy in high-grade ovarian cancer," is designed as a prospective, monocentric, observational cohort study utilizing biological material. The primary objective of this research is to evaluate the functional capacity of the U-Cup bioreactor to predict the clinical response to standard chemotherapy in patient-derived high-grade ovarian cancer tissues maintained in perfusion culture. As a secondary objective, the study seeks to develop a high-throughput platform for the personalized assessment of therapeutic responses. This platform will specifically focus on ovarian cancer cases that demonstrate resistance to standard chemotherapy, exploring their sensitivity to alternative metabolic-driven therapies. The study population consists of women diagnosed with high-grade serous ovarian carcinoma who have not previously undergone chemotherapy. These patients are candidates for surgical intervention at the UOC Ginecologia Oncologica De Iaco - IRCCS AOUBO. Eligibility for the study is strictly defined by specific inclusion and exclusion criteria to ensure a homogeneous and clinically relevant cohort. Inclusion requires patients to be 25 years of age or older, provide informed consent, and have a confirmed histological or surgical diagnosis of high-grade serous ovarian cancer. Furthermore, eligible participants must not have undergone prior surgical treatment for this malignancy and must have sufficient primary or metastatic tumor tissue available for sampling. Conversely, the study excludes patients presenting with significant comorbidities or those affected by other concurrent malignancies. Over a planned duration of 36 months, the study aims to enroll a total of 120 patients. For all parameters measured, including drug response tests related to the secondary objective, data will first undergo the Shapiro-Wilk test to assess the normality of distribution. Continuous variables following a normal distribution will be analyzed using the Student's T-test, while non-normally distributed variables will be evaluated using the Mann-Whitney U test. Categorical variables will be assessed using the Chi-square test or Fisher's exact test, depending on the distribution characteristics. Specifically, for the primary objective, clinical data will be utilized to group patients based on their Chemotherapy Response Score (CRS), comparing those with a high response (CRS3) against those with partial or no response (CRS1/2). The analysis will focus on identifying significant differences in proliferation variation (measured via Ki67-positive nuclei), apoptosis (cleaved Caspase-3 positivity), and necrosis (as evaluated by pathological assessment of HE staining) between SCT-treated and untreated samples. This comparative analysis aims to determine if one or more of these biological parameters can reliably predict a patient's clinical response to standard treatment. To further refine these findings, Area Under the ROC Curve (AUROC) analysis and logistic regression will be employed to define optimal threshold values. These thresholds will be used to discriminate between CRS3 and CRS1/2 patients with high sensitivity and specificity, ultimately validating the bioreactor platform as a predictive tool for personalized oncology.

NCT Number	NCT07461207
Lead Sponsor	IRCCS Azienda Ospedaliero-Universitaria di Bologna
Conditions	High-grade Serous Ovarian Carcinoma (HGSOC)
Enrollment	120 participants
Start Date	2026-03
Primary Completion	2029-03 (estimated)
Study Completion	2029-03 (estimated)
Updated on ClinicalTrials.gov	2026-03-12