Rexin-G is a pathotropic retroviral vector displaying a von Willebrand factor-targeting motif and expressing a dominant negative cyclin G1 gene. We undertook a phase I trial of intravenous (i.v.) administration of Rexin-G in patients with gemcitabine refractory, metastatic pancreatic adenocarcinoma. Twelve patients were treated. Dose escalation was performed from a dose of 1 x 10(11) colony forming units (CFU) per cycle to 6 x 10(11) CFU per cycle. The treatment was well tolerated. One dose-limiting toxicity (DLT) at dose level 2 (1.5 x 10(11) CFU per cycle) was observed, consisting of grade 3 transaminitis. There was no detection of replication-competent virus in patients' peripheral blood mononuclear cells (PBMCs) or viral integration in DNA obtained from PBMCs, and no development of neutralizing antibodies. No evidence of antitumor activity was observed. The best objective response was progressive disease in 11 of the 12 study patients, while 1 patient showed radiographically stable disease with clinical deterioration and increase in the CA19.9 tumor marker. Median time to progression was 32 days. The median duration of survival of the study patients was 3.5 months from treatment initiation. Rexin-G is well tolerated in doses up to 6 x 10(11) CFU in patients with recurrent pancreatic cancer, but there was no evidence of clinical antitumor activity.