68Ga-FAPI-46 PET-CT for Initial Staging of Curatively Treated Gastric Adenocarcinoma

The primary objective of this study is to estimate the proportion of patients with gastric cancer, specifically stage ≥ II gastric adenocarcinomas or signet-ring cell adenocarcinomas eligible for curative treatment, who experience an appropriate change in TNM classification following the addition of 68Ga-FAPI-46 PET-CT to reference examinations during initial staging. This evaluation aims to determine the clinical utility of this imaging modality in refining cancer staging accuracy.

The secondary objectives include:

• Estimation of the proportion of patients whose TNM classification, determined via CT imaging alone, is modified after 68Ga-FAPI-46 PET-CT.
• Estimation of the proportion of patients experiencing an appropriate change in M status following the addition of 68Ga-FAPI-46 PET-CT to reference examinations.
• Estimation of the proportion of patients whose therapeutic management is altered due to the addition of 68Ga-FAPI-46 PET-CT.
• Estimation of the number of additional tumor lesions detected by 68Ga-FAPI-46 PET-CT compared to reference examinations.
• Estimation of the inter-observer reproducibility of 68Ga-FAPI-46 PET-CT interpretation.

The sponsor did not provide information regarding the total number of participants. The study population consists of patients diagnosed with gastric cancer, specifically involving gastric adenocarcinoma at stage II or higher, or signet-ring cell adenocarcinoma of any stage that is eligible for curative treatment. The participants include both male and female individuals, including vulnerable populations, within the age ranges corresponding to codes 3 and 4. Inclusion requires participants to be older than 18 years at the time of consent and to be beneficiaries of social security insurance. The primary objective is to estimate the proportion of patients exhibiting an appropriate change in TNM classification following the administration of 68Ga-FAPI-46 PET-CT during initial staging.

This phase II clinical trial is designed to evaluate the diagnostic utility of 68Ga-FAPI-46 PET-CT in the initial staging of patients with gastric cancer. The study focuses on individuals diagnosed with stage ≥ II gastric adenocarcinoma or signet-ring cell adenocarcinoma who are candidates for curative treatment. The primary objective is to estimate the proportion of patients experiencing an appropriate change in TNM classification following the addition of 68Ga-FAPI-46 PET-CT to standard reference examinations, which include laparoscopy and thoraco-abdominopelvic CT imaging. Secondary endpoints include assessing changes in nodal or metastatic status, alterations in therapeutic management, and the inter-observer reliability of imaging interpretation. The investigational product involves an intravenous injection of 68Ga-FAPI-46, which may be derived from various radionuclide generator sources. The total study duration is estimated to span from June 2026 to June 2029.

The investigational product 68Ga-FAPI-46 is administered as a solution for injection via intravenous injection at a dose of 350 MBq. The active substance is (s)-2,2',2''-(10-(2-(4-(3-((4-(2-(2-cyano-4,4-difluoropyrrolidin-1-yl)-2-oxoethylcarbamoyl)-quinolin-6-yl)(methyl)amino)-propyl)piperazin-1-yl)-2-oxoethyl)-68ga-[1,4,7,10]-tetraazacyclododecane-1,4,7-triyl)triacetate.

The study utilizes several radionuclide generators as test products. These include various versions of the GalliaPharm generator (3.70 GBq, 3.33 GBq, 2.96 GBq, 2.59 GBq, 2.22 GBq, and 1.85 GBq) and the Galliad generator (0.74 to 1.85 GBq). The GalliaPharm generators, containing gallium (68ga) chloride, are provided as a radionuclide generator or solution for injection and are administered via intravenous injection at a dose of 350 MBq. The Galliad generator, containing germanium (68ge) chloride, is provided as a solution for injection and is administered via intravenous injection at a dose of 350 MBq.

The primary efficacy endpoint is the proportion of patients with gastric cancer who exhibit an appropriate change in TNM classification following the addition of 68Ga-FAPI-46 PET-CT to the reference examinations during initial staging. This assessment includes staging via laparoscopy.

Secondary endpoints include:

• The proportion of patients showing an appropriate change in N status and/or M status of the TNM classification, as determined by standard thoraco-abdominopelvic CT imaging alone, after the addition of 68Ga-FAPI-46 PET-CT.
• The proportion of patients showing an appropriate change in M status determined by standard thoraco-abdominopelvic CT imaging alone following the addition of 68Ga-FAPI-46 PET-CT.
• The proportion of patients experiencing an appropriate addition or removal of specific elements of therapeutic management, such as curative surgical treatment, neoadjuvant or adjuvant treatment by chemotherapy or radiotherapy, surgical resection complementary, or palliative treatment by chemotherapy or other systemic treatment, following the addition of 68Ga-FAPI-46 PET-CT.
• The average number of tumor, lymph node, or distant lesions detected by 68Ga-FAPI-46 PET-CT compared to the number detected by reference staging.
• The Cohen's kappa coefficient used to measure the inter-observer reliability of 68Ga-FAPI-46 PET/CT interpretation between the coordinating center and investigating center observers.