Comparative Evaluation of 68Ga-Gozetotide and 89Zr-DFO-Girentuximab PET Imaging in Primary, Recurrent, or Metastatic Clear Cell Renal Cell Carcinoma

The primary objective of this study is to conduct an intrapatient comparison of the tumor detection rates of **68Ga-gozetotide (PSMA)** PET and **89Zr-girentuximab** PET in patients suspected of having primary, recurrent, or metastatic clear cell renal cell carcinoma (ccRCC). This comparison will be performed both visually and semi-quantitatively. The clinical relevance of this objective lies in its potential to enhance diagnostic accuracy and improve the management of ccRCC by identifying the most effective imaging modality for detecting tumors in this patient population.

The clinical trial involves participants diagnosed with or suspected of having **metastatic renal cell carcinoma**. The study population includes both male and female subjects aged 18 years and older. Participants are selected based on a suspicion of metastatic clear cell renal cell carcinoma (ccRCC) as indicated by conventional contrast-enhanced CT scans conducted within four weeks prior to the PET scan. The trial does not focus on a vulnerable population, and the sponsor has not provided the total number of participants. The study does not specify any particular lifestyle considerations such as diet or physical activity. Key inclusion criteria include being 18 years or older and having a suspicion of metastatic ccRCC, with or without biopsy confirmation, and regardless of whether the primary tumor is present.

The clinical trial is designed to evaluate the tumor detection rates of **68Ga-gozetotide (PSMA)** PET and **89Zr-DFO-girentuximab** PET in patients with suspected primary, recurrent, or metastatic clear cell renal cell carcinoma (ccRCC). This is a randomized, double-blind, controlled study with an estimated duration from January 1, 2025, to January 1, 2027. The trial will involve a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age (≥ 18 years) and suspicion of metastatic ccRCC on conventional contrast-enhanced CT. Participants will undergo PET-CT scans using both investigational products, with follow-up visits scheduled to monitor safety and efficacy outcomes.

The primary endpoint is to compare the tumor detectability of the two PET-CT methods, while secondary endpoints include semi-quantitative assessments of SUVmax in primary tumors and metastases, as well as tumor-to-background ratios. Participants are expected to be involved in the study for the entire trial duration unless early termination is warranted due to adverse events, withdrawal of consent, or protocol non-compliance. The investigational products, **Zr-DFO-girentuximab** and **Gallium (68Ga) PSMA-11 (gozetotide)**, will be administered intravenously as solutions for injection, with maximum daily doses of 37 MBq and 259 MBq, respectively. The trial is authorized in the Netherlands and aims to provide insights into the comparative effectiveness of these imaging agents in detecting ccRCC.

The clinical trial involves the administration of **Zr-DFO-girentuximab**, an experimental medication formulated as a **solution for injection**. The active substance, **zirconium (89Zr) girentuximab**, is a protein-based compound. The medication is administered via **intravenous administration**. The maximum daily and total dose is 37 MBq (megabecquerels), with a treatment period limited to a single day. This investigational product is not a pediatric formulation and is not classified as an orphan drug. The administration of this medication is monitored to ensure participant compliance with the dosing schedule.

Another experimental treatment used in the study is **Gallium (68Ga) PSMA-11 (gozetotide)**, prepared using the PSMA-11 Sterile Cold Kit. This medication is also a **solution for injection** and contains the active substance **gallium (68Ga) gozetotide**, which is of chemical origin. The administration route is **intravenous**, with a maximum daily and total dose of 259 MBq. Similar to the first investigational product, this treatment is not intended for pediatric use and is not designated as an orphan drug. Compliance with the dosing regimen is closely monitored throughout the trial.

Both investigational products are utilized in the study to compare their tumor detection rates in patients with suspected primary, recurrent, or metastatic clear cell renal cell carcinoma. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. The study is designed to ensure rigorous monitoring of drug administration and participant adherence to the prescribed dosing schedules.

The efficacy of the investigational products in this clinical trial will be assessed by evaluating the tumor detection rates of **68Ga-gozetotide (PSMA) PET-CT** and **89Zr-DFO-girentuximab PET-CT** in patients with suspected metastatic clear cell renal cell carcinoma (ccRCC). The primary endpoint involves a descriptive comparison of the tumor detectability of these imaging modalities, with the conventional contrast-enhanced CT serving as the denominator. This comparison aims to determine the relative effectiveness of each PET-CT method in identifying tumors.

Secondary endpoints include the semi-quantitative assessment of the maximum standardized uptake value (SUVmax) in primary tumors, if present, and in metastases, using lesion-based analyses. Additionally, the tumor-to-background ratio for both primary tumors and metastases will be evaluated. These assessments will provide further insights into the imaging performance and potential diagnostic advantages of the PET-CT methods under investigation.