A phase I trial of of cixutumumab (C) (IMC-A12) and sorafenib (S) for treatment of advanced hepatocellular carcinoma (HCC).

293 Background: The insulin growth factor (IGF) pathway is activated in hepatocarcinogenesis. C is a monoclonal antibody against human insulin-like growth factor-1 receptor (IGF-1R). In vivo HCC models show activated IGF signaling and antitumor effects due to C. Given the cross-talk between the IGF and VEGF pathways, the combination of C and S was chosen for study. Methods: This study evaluated the safety of C (2, 4 or 6 mg/kg) IV weekly with standard doses of S (400 mg po bid) in patients (pts) with HCC without standard curative options. Eligibility criteria included: no prior systemic therapy, Child-Pugh score of A or B7, ECOG 0 or 1, platelets > 75,000/mm3, and albumin > 2.8 g/dl. The study used a standard 3+3 design. One cycle was 28 days. Results: A total of 21 pts (17 males and 4 females) were enrolled; mean age was 63 years (43-85); 10 Asian, 4 Hispanic, 5 White, 1 Black, and 1 Native American. There were 3 dose limiting toxicities (DLTs); grade 3 hyperglycemia, grade 3 hypophosphatemia, and grade ...