Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Abou-Alfa GK

PROVIDER: S-EPMC3901953 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Abou-Alfa Ghassan K GK Capanu Marinela M O'Reilly Eileen M EM Ma Jennifer J Chou Joanne F JF Gansukh Bolorsukh B Shia Jinru J Kalin Marcia M Katz Seth S Abad Leslie L Reidy-Lagunes Diane L DL Kelsen David P DP Chen Helen X HX Saltz Leonard B LB

Journal of hepatology 20130914 2

<h4>Background & aims</h4>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.<h4>Methods</h4>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 we ...[more]

PMID: 24045151

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Dataset Information

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

Background & aims

Methods

Results

Conclusions

Publications

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

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