A Phase I Study of the Naturally Occurring Bioactive, Opioid Growth Factor, in Patients with Unresectable Hepatocellular Cancer

Hepatocellular cancer (HCC), one of the world's most deadly tumors, and its incidence in the US continues to rise. Surgical resection/transplantation offers the only hope for cure; however, many patients are not candidates and have limited therapeutic options. Opioid growth factor (OGF) is a naturally occurring bioactive endogenous pentapeptide that inhibits growth of human HCC cell lines <i>in vitro</i> by a receptor-mediated mechanism and inhibits progression of tumors in nude mice. Based on these preclinical studies, we conducted a phase I clinical trial with dose escalation (standard 3 + 3 protocol) of OGF to determine the maximum tolerated dose in HCC patients with concomitant liver disease (NCT00706576). Fifteen doses were administered to 14 patients with a maximum 300 µg/kg dose. No Grade 3 toxicities were encountered in the study group. This dose exceeds the maximum tolerated dose reached in our previous phase I pancreatic cancer trial. We conclude that OGF can be safely administered to patients with HCC and concomitant liver disease without significant toxicities up to a dose of 300 µg/kg. The result of this trial provides data on toxicity and the pharmacokinetics of OGF in patients with HCC and liver disease and lays the groundwork for additional studies.