124I-cG250 PET scan for early detection of response to sunitinib in patients (Pts) with metastatic clear cell renal cell carcinoma (MccRCC).

Abstract

362 Background: Mutation and/or methylation of the von Hippel-Lindau gene leading to overexpression of hypoxia-inducible factor-1 alpha (HIF1α) has been implicated as a driving event in the pathogenesis of ccRCC. Downstream effectors of HIF1α such as VEGF have become key targets of novel therapies for MccRCC (eg, sunitinib (S)). Carbonic anhydrase-IX (CAIX) transcription is also regulated by HIF1α and is overexpressed in ~95% of ccRCC. Linkage of cG250 (Girentuximab), a chimeric antibody to CAIX, to radioactive iodine (124I), has resulted in a radiotracer specific for ccRCC; 124I-cG250 (124I-Girentuximab) PET/CT demonstrated a sensitivity of 86% and a specificity of 87% for detecting primary ccRCC (Uzzo AUA 2010). Since responses to targeted therapies likely occur on a molecular level before they are detectable with standard imaging, we hypothesize that 124I-cG250 PET/CT could allow earlier recognition of response or progression to S than CT in pts with MccRCC. Methods: This is a pilot study of 124I-cG250 PET/CT in 25 pts with MccRCC planned to begin treatment (Tx) with S. 124I-cG250 PET/CT will be assessed for its ability to predict Tx response during (days 25–28) and at completion (days 39-42) of the first cycle of therapy, in comparison to standard CT imaging at routine intervals. PET/CT and CT will each be interpreted by 1 nuclear medicine physician, who will be blinded to the results of the comparator imaging modality, but aware of the clinical history of the pts. Eligibility include age ≥18, ECOG PS < 2, histologically confirmed MccRCC, Tx planned with S, and radiographic evidence of unidimensionally measurable disease with at least one lesion ≥2 cm in diameter on 16-slice multi-detector CT. Key exclusion criteria include uncontrolled/unstable hyperthyroidism or Grave’s Disease, unstable cardiac disease and uncontrolled seizure disorder or history of CVA or TIA within the past 12 months. Results: NA. Conclusions: This is the first clinical trial to prospectively evaluate the use of a histologically specific imaging modality to measure early changes in ccRCC CAIX protein expression as a predictor of response to biologically targeted Tx. Enrollment will commence in November 2011.