Diagnostic accuracy and clinical value of [68Ga]Ga-FAPI-46 PET/CT for staging patients with ovarian cancer: study protocol for a prospective clinical trial.

Background: [F]Fluorodeoxyglucose ([F]FDG) positron emission tomography (PET) is recommended during diagnostic work-up for ovarian cancer; however, [F]FDG PET has several inherent limitations. The novel oncologic PET-tracer fibroblast activation protein inhibitor (FAPI) has demonstrated promising results in multiple cancer types, including ovarian cancer, and could overcome the limitations of [F]FDG PET; however, high-quality clinical studies are lacking. The primary objective of the present study is to compare the diagnostic accuracy of [Ga]Ga-FAPI-46 PET/CT and [F]FDG PET/CT in ovarian cancer patients and to investigate how this potential difference impacts staging and patient management.

Methods And Design: Fifty consecutive ovarian cancer patients will be recruited from Aalborg University Hospital, Denmark. This study will be a single-center, prospective, exploratory clinical trial that adheres to the standards for reporting diagnostic accuracy studies (STARD). This study will be conducted under continuous Good Clinical Practice monitoring. The eligibility criteria for patients are as follows: (1) biopsy verified newly diagnosed ovarian cancer or a high risk of ovarian cancer and referred for primary staging with [F]FDG PET/CT; and (2) resectable disease, i.e., candidate for primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery. All recruited study subjects will undergo [Ga]Ga-FAPI-46 PET/CT at primary staging, before primary debulking surgery or neoadjuvant chemotherapy (Group A + B), in addition to conventional imaging (including [F]FDG PET/CT). Study subjects in Group B will undergo an additional [Ga]Ga-FAPI-46 PET/CT following neoadjuvant chemotherapy prior to interval debulking surgery. The results of the study-related [Ga]Ga-FAPI-46 PET/CTs will be blinded, and treatment allocation will be based on common clinical practice in accordance with current guidelines. The histopathology of surgical specimens will serve as a reference standard. A recruitment period of 2 years is estimated; the trial is currently recruiting.

Discussion: To our knowledge, this trial represents the largest, most extensive, and most meticulous prospective FAPI PET study conducted in patients with ovarian cancer thus far. This study aims to obtain a reliable estimation of the diagnostic accuracy of [Ga]Ga-FAPI-46 PET/CT, shed light on the clinical importance of [Ga]Ga-FAPI-46 PET/CT, and examine the potential applicability of [Ga]Ga-FAPI-46 PET/CT for evaluating chemotherapy response.

Trial Registration: clinicaltrials.gov: NCT05903807, 2nd June 2023; and euclinicaltrials.eu EU CT Number: 2023-505938-98-00, authorized 11th September 2023.