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

J Hepatol 2014 Feb 14;60(2):319-24. Epub 2013 Sep 14.

Department of Internal Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; Department of Internal Medicine, Weill Medical College at Cornell University, New York, NY, United States.

Background & Aims: IGF-IR is implicated in hepatic carcinogenesis. This and preliminary evidence of biological activity of anti-IGF-1R monoclonal antibody cixutumumab in phase I trials prompted this phase II study.

Methods: Patients with advanced HCC, Child-Pugh A-B8, received cixutumumab 6mg/kg weekly, in a Simon two-stage design study, with the primary endpoints being 4-month PFS and RECIST-defined response rate. Tissue and circulating markers plus different HCC scoring systems were evaluated for correlation with PFS and OS.

Results: As a result of pre-specified futility criteria, only stage 1 was accrued: N=24: median age 67.5 years (range 49-83), KPS 80% (70-90%), 20 males (83%), 9 stage III (37%)/15 stage IV (63%), 18 Child-Pugh A (75%), 11 HBV (46%)/10 HCV (42%)/11 alcoholic cirrhosis (46%)/2 NASH (8%), 11 (46%) diabetic. Median number of doses: 7 (range 1-140). Grade 3/4 toxicities >10% included: diabetes, elevated liver function tests, hyponatremia, and lymphopenia. Four-month PFS was 30% (95% CI 13-48), and there were no objective responses. Median overall survival was 8 months (95% CI 5.8-14). IGF-R1 staining did not correlate with outcome. Elevated IGFBP-1 correlated with improved PFS (1.2 [95% CI 1-1.4]; p 0.009) and OS (1.2 [95% CI 1.1-1.4]; p 0.003).

Conclusions: Cixutumumab monotherapy did not have clinically meaningful activity in this unselected HCC population. Grade 3-4 hyperglycemia occurred in 46% of patients. Elevated IGFBP-1 correlated with improved PFS and OS.

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http://dx.doi.org/10.1016/j.jhep.2013.09.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901953PMC
February 2014
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