Phase I, Pharmacokinetic, and Pharmacodynamic Study of Intravenously Administered Ad5CMV-p53, an Adenoviral Vector Containing the Wild-Type p53 Gene, in Patients With Advanced Cancer

Purpose The purpose of this study was to assess the feasibility of administering Ad5CMV-p53, an adenoviral vector containing the wild-type p53 gene to patients with advanced malignancies, characterize the pertinent pharmacokinetic parameters, identify evidence of viral uptake in both normal and tumor tissue, and seek evidence of antitumor activity. Methods Patients were treated with escalating doses of Ad5CMV-p53 intravenously over 30 minutes on days 1, 2, and 3, every 28 days. The clearance of circulating Ad5CMV-p53 (INGN 201) DNA was characterized in the plasma and paired tumor and skin biopsies were performed in patients treated at the two highest dose levels to assess vector uptake into tissues. Results Seventeen patients received 36 courses of Ad5CMV-p53 at doses ranging from 3 × 1010 to 3 × 1012 virus particles (vp). Fatigue, nausea, vomiting, and fever were common, but rarely severe. Abnormalities of coagulation parameters, including decreases in fibrinogen and increases in fibrin degradation produ...