89Zr-girentuximab ) Dosimetry in CCRC Study - ZIR-DOSE

The study is designed to explore the safety and tolerability as well as diagnostic 89Zr-girentuximab for imaging CCRC by PET/CT. This study does not offer any treatment for patients with CCRC; therefore, patients will be offered state of the art therapeutic options after imaging with the study drug 89Zr-girentuximab. Cancer treatment will not be delayed by study participation.

The identification of RCC is crucial for planning possible surgery and treatment. The aim of this study is to investigate the safety, tolerability, radiation dosimetry, as well as the diagnostic performance of 89Zr-girentuximab PET/CT in patients with suspected CCRC. The results of this study will be used to pave the way for further studies with 89Zr-girentuximab as a PET/CT imaging agent which was shown to have higher diagnostic resolution 124I-girentuximab in animal studies due to prolonged trapping of the radiolabel in the tumour and simultaneous washout from normal tissues. It is anticipated to develop 89Zr-girentuximab as an improved imaging agent for CCRC. This will be an exploratory, open-label, Phase 1 study to evaluate safety, tolerability, whole body dosimetry, and imaging properties of 89Zr-girentuximab, when image acquisition is made using different PET reconstruction methods, namely time-of-flight (TOF-PET) and conventional (PET) reconstruction, in order to estimate a possible impact of variable scanner technology on image quality variability in a planned multi-centre study. In addition, different acquisition durations (5 -20 min) will be explored using an activity dose of 37 mBq (1 mCi), in order to establish, whether acquisition time has an impact on diagnostic performance. It is anticipated to recruit 8-10 patients with suspected or established CCRC to * Receive a slow intravenous injection with 89Zr-girentuximab (1-2 minutes slow bolus injection), followed by * Dosimetric and tumour PET/CT imaging. The study duration will be approximately 12 months. Primary endpoint is safety, a part of which is determining the effective dose (mSv/MBq) to the whole body, and absorbed dose (mGy/MBq) to individually discernible organs. Secondary endpoints include physicians assessment of PET image quality and tumour detectability comparing the following reconstruction settings: TOF-PET PET 37 MBq 5, 10, 15 and 20 min 5, 10, 15 and 20 min Additionally, images partitioned to acquisition times of 5, 10, 15 and 20 min will be comparatively analysed in a blinded read. In order to comprehensively characterise safety and tolerability, standard safety parameters (labs, 12-lead ECG, adverse events, and concomitant medications) will be systematically assessed at baseline and at appropriate intervals post dosing. Patients with clinical suspicion of CCRC, based on imaging evidence of a renal mass, requiring further diagnostic work-up, or patients with established diagnosis of CCRC requiring imaging for recurrent disease will be recruited by the urological service of the study centre, and undergo a formal screening visit, during which the study schedule will be planned, and consent obtained. All successfully screened patients will be injected with 89Zr-girentuximab on Day 0 by the nuclear medicine service, followed by: Sequential static whole body PET/CT imaging: For dosimetry analysis, biodistribution whole body PET/CT imaging will be performed at 0.5, 4, 24, 72 and 168±24 h (Day 7±1) post injection, using low dose CT. Patients will be imaged on a TOF-PET scanner, offering the possibility of TOF (time-of-flight) and non-TOF reconstruction. Comparative tumour PET/CT imaging: On Days 3 and 7±1 (after the biodistribution whole body scans on Days 3 and 7), tumour imaging will be performed using gated or list mode acquisition, for generation of sub-partitioned data. Such data allow the mathematical generation of statistically independent images for various dose levels, based on the actual dose administered in the trial. Acquisition will be for 20 min. An end of study visit will be conducted on Day 8±1. 89Zr-girentuximab dosimetry will be centrally analysed for absorbed organ and whole body doses in a standardised fashion. In addition, tumour absorbed doses will be determined for scientific purposes (estimation of achievable tumour doses of therapeutic nuclides labelled to girentuximab). All image data analyses will be performed / confirmed centrally.