Phase I Trial of Intraperitoneal Injection of the E1B-55-kd-Gene–Deleted Adenovirus ONYX-015 (dl1520) Given on Days 1 Through 5 Every 3 Weeks in Patients With Recurrent/Refractory Epithelial Ovarian Cancer

PURPOSE: Resistance to chemotherapy in ovarian cancer is frequently associated with mutations in the p53 gene. The adenovirus dl1520 (ONYX-015) with the E1B 55-kd gene deleted, allowing selective replication in and lysis of p53-deficient tumor cells, has shown preclinical efficacy against p53-deficient nude mouse-human ovarian carcinomatosis xenografts. PATIENTS AND METHODS: We undertook a phase I trial of intraperitoneal dl1520 in patients with recurrent ovarian cancer. Sixteen women with recurrent/refractory ovarian cancer received 35 cycles (median, two cycles) of dl1520 delivered on days 1 through 5 in four dose cohorts: 1 × 109 plaque forming units (pfu), 1 × 1010 pfu, 3 × 1010 pfu, and 1 × 1011 pfu. RESULTS: The most common significant toxicities related to virus administration were flu-like symptoms, emesis, and abdominal pain. One patient receiving 1 × 1010 pfu developed common toxicity criteria grade 3 abdominal pain and diarrhea, which was dose-limiting. The maximum-tolerated dose was not reache...