Cixutumumab is a monoclonal antibody that has potent anti-tumor activity in a variety of cell-lines and xenografts, so researchers from the Cincinnati Children’s Hospital Medical Center and other institutions sought to determine the maximum-tolerated dose and dose-limiting toxicities of the drug when administered in combination with temsirolimus to children with tumors that are refractory to therapy.
In this study, which was published online ahead of print in Clinical Cancer Research, cixutumumab and temsirolimus were given intravenously once every 7 days in 28-day cycles to 39 patients with a median age of 11.8 years.
Four dose levels of cixutumumab and temsirolimus were given (6 mg/kg and 15 mg/m2; 6 mg/kg and 10 mg/m2; 4 mg/kg and 8 mg/m2; and 6 mg/kg and 8 mg/m2 ) and of those patients enrolled in the trial, 33 were assessable for resulting toxicities.
Mucositis was the predominant dose-limiting toxicity. Other toxicities included hypercholesterolemia, fatigue, thrombocytopenia, and increased ALT. Based on the PK parameters of the study, the authors concluded that the recommended doses for a future phase II study of cixutumumab and temsirolimus are 6 mg/kg and 8 mg/m2, respectively.