A phase II study of cixutumumab (IMC-A12, NSC742460) in advanced hepatocellular carcinoma.

摘要: Background & Aims IGF-IR is implicated in hepatic carcinogenesis. This and preliminary evidence of biological activity anti-IGF-1R monoclonal antibody cixutumumab phase I trials prompted this II study. Methods Patients with advanced HCC, Child-Pugh A-B8, received 6mg/kg weekly, a Simon two-stage design study, the primary endpoints being 4-month PFS RECIST-defined response rate. Tissue circulating markers plus different HCC scoring systems were evaluated for correlation OS. Results As result pre-specified futility criteria, only stage 1 was accrued: N=24: median age 67.5years (range 49–83), KPS 80% (70–90%), 20 males (83%), 9 III (37%)/15 IV (63%), 18 A (75%), 11 HBV (46%)/10 HCV (42%)/11 alcoholic cirrhosis (46%)/2 NASH (8%), (46%) diabetic. Median number doses: 7 1–140). Grade 3/4 toxicities >10% included: diabetes, elevated liver function tests, hyponatremia, lymphopenia. Four-month 30% (95% CI 13–48), there no objective responses. overall survival 8months 5.8–14). IGF-R1 staining did not correlate outcome. Elevated IGFBP-1 correlated improved (1.2 [95% 1–1.4]; p 0.009) OS 1.1–1.4]; 0.003). Conclusions Cixutumumab monotherapy have clinically meaningful unselected population. 3–4 hyperglycemia occurred 46% patients.