Evaluation of Nuclear Magnetic Resonance-Derived Metabolomics and MRI Techniques Using Gadoteric Acid and Pyruvic Acid in Ovarian Cancer Diagnostics

The primary objective of the study titled "IMPROCAS - Improved Prediction of Ovarian Cancer Surgery" is to evaluate the efficacy of **nuclear magnetic resonance (NMR)-derived metabolomics** from blood samples, alongside functional and metabolic MRI techniques, in enhancing the diagnostic accuracy for **ovarian cancer**. This investigation aims to develop a model that can accurately identify ovarian cancer and assess disease severity, thereby improving diagnostic precision and informing treatment strategies.

The clinical trial focuses on **ovarian cancer** and involves a study population exclusively composed of female participants, aged between 18 and 85 years. The trial does not include male subjects or vulnerable populations. Participants were selected based on the suspicion of epithelial ovarian cancer and their referral to the Department of Gynaecology and Obstetrics at AUH, with selection for a multidisciplinary team (MDT) evaluation. Additionally, participants are required to understand Danish. The sponsor has not provided information regarding the total number of participants. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial aims to enhance ovarian cancer diagnostics through advanced imaging and metabolomics techniques.

The clinical trial is designed to evaluate the efficacy of nuclear magnetic resonance (NMR)-derived metabolomics and advanced MRI techniques in improving the diagnostic accuracy of **ovarian cancer**. This is a Phase 4, randomized, double-blind, controlled trial, with an estimated duration from August 2023 to August 2028. The trial involves the administration of two MRI contrast agents, **gadoteric acid** and **pyruvic acid**, both delivered via intravenous injection. The primary objective is to assess the diagnostic performance of various MRI techniques and develop a diagnostic algorithm for accurate classification and staging of ovarian cancer. Secondary objectives include evaluating the repeatability and reproducibility of multiparametric pelvic MRI.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as suspected epithelial ovarian cancer, age between 18 and 85 years, and understanding of Danish. Follow-up visits will be scheduled to monitor the diagnostic procedures and collect blood samples for NMR-derived analyses. The end-of-study visit will conclude the participant's involvement, which is expected to last up to one year. Conditions that may lead to early termination from the study include adverse reactions to the contrast agents or withdrawal of consent by the participant.

The clinical trial involves the administration of two experimental medications. The first medication is **Dotarem**, a solution for injection containing the active substance **gadoteric acid**. This pharmaceutical form is provided in a single-dose container for intravenous administration. The dosage is calculated based on body weight, with a maximum daily and total dose of 0.1 mmol/kg. The administration is intended as an **MRI contrast agent** to enhance imaging quality. The product is manufactured by Guerbet and is not a pediatric formulation. The treatment period is limited to a single day, and participant compliance is monitored through standard clinical trial procedures.

The second experimental medication is **Hyperpolarized [1-13C]pyruvate**, also administered as an injection. The active substance in this formulation is **pyruvic acid**, and it is also delivered intravenously. The dosage is set at a maximum of 0.43 ml/kg per day, with the same limit for the total dose. This agent is used as an **MRI contrast agent** to improve the diagnostic accuracy of ovarian cancer. The product is developed by Aarhus University and is not intended for pediatric use. Similar to the first medication, the treatment period is restricted to one day, and compliance is ensured through established monitoring protocols.

Both medications are chemically derived and are utilized in the trial to investigate their potential in enhancing the diagnostic capabilities of MRI in ovarian cancer. The trial does not include any non-experimental treatments such as standard-of-care therapy or placebo. The administration of these agents is conducted under controlled conditions to ensure participant safety and data integrity.

Efficacy in the clinical trial titled "IMPROCAS - Improved Prediction of Ovarian Cancer Surgery" will be assessed using several primary and secondary endpoints. The primary endpoints include evaluating the diagnostic performance of Dynamic Contrast-Enhanced (DCE) MRI, Diffusion Kurtosis Imaging (DKI), and **31P Magnetic Resonance Spectroscopy (MRS)**. Additionally, the trial aims to create a diagnostic algorithm to assist clinicians in accurately classifying the diagnosis and FIGO-staging of ovarian cancer. The contribution of Hyperpolarized **13C MRI** to the correct histopathological diagnosis and staging of ovarian cancer will also be assessed. Furthermore, NMR-derived analyses from blood samples will be evaluated for their ability to distinguish patients with cancer from those without and to predict the correct histopathological diagnosis.

Secondary endpoints focus on assessing the repeatability and reproducibility of multiparametric pelvic MRI in patients suspected of having ovarian cancer. The NMR-derived analyses from blood samples will also be evaluated for their ability to predict surgical resectability. These efficacy parameters will be measured and collected using advanced imaging techniques and blood sample analyses, with the aim of improving diagnostic accuracy and treatment planning for ovarian cancer.