A phase I clinical trial of Ad5/3-Δ24, a novel serotype-chimeric, infectivity-enhanced, conditionally-replicative adenovirus (CRAd), in patients with recurrent ovarian cancer

Objective. The conditionally replicative adenovirus Ad5/3-Delta 24 has a type-3 knob incorporated into the type-5 fiber that facilitates enhanced ovarian cancer infectivity. Preclinical studies have shown that Ad5/3-Delta 24 achieves significant oncolysis and anti-tumor activity in ovarian cancer models. The purpose of this study was to evaluate in a phase I trial the feasibility and safety of intraperitoneal (IP) Ad5/3-Delta 24 in recurrent ovarian cancer patients. Methods. Eligible patients were treated with IP Ad5/3-Delta 24 for 3 consecutive days in one of three dose cohorts ranging 1 x 10(10)-1 x 10(12) vp. Toxicity was assessed utilizing CfC grading and efficacy with RECIST. Ascites, serum, and other samples were obtained to evaluate gene transfer, generation of wildtype virus, viral shedding, and antibody response. Results. Nine of 10 patients completed treatment per protocol. A total of 15 vector-related adverse events were experienced in 5 patients. These events included fever or chills, nausea, fatigue, and myalgia. All were grades 1-2 in nature, transient, and medically managed. Of the 8 treated patients evaluable for response, six patients had stable disease and 2 patients had progressive disease. Three patients had decreased, FA-125 from pretreatment levels one month after treatment Ancillary biologic studies indicated Ad5/3-Delta 24 replication in patients in the higher dose cohorts. All patients experienced an anti-adenoviral neutralizing antibody, effect. Conclusions. This study suggests the feasibility and safety of a serotype chimeric infectivity-enhanced CRAd, Ad5/3-Delta 24, as a potential therapeutic option for recurrent ovarian cancer patients. (C) 2013 Elsevier Inc. All rights reserved.