A phase I trial of intraperitoneal GEN-1, an IL-12 plasmid formulated with PEG-PEI-cholesterol lipopolymer, administered with pegylated liposomal doxorubicin in patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancers: An NRG Oncology/Gynecologic Oncology Group study

Objective. The study's purpose was to assess safety and efficacy of escalating doses of weekly GEN-1 with pegylated liposomal doxorubicin (PLD) in patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancers (EOC). Methods. Patients had persistent or recurrent platinum-resistant EOC. The trial was a standard 3 + 3 phase I dose escalation design with patients receiving intravenous PLD 40 mg/m(2) (dose level 1 and 2) or 50 mg/m(2) (dose level 3) every 28 days and intraperitoneal GEN-1 at 24 mg/m(2) (dose level 1) or 36 mg/m(2) (dose level 2 and 3) on days 1, 8,15, and 22 of a 28 day cycle. Cycles were repeated every 28 days until disease progression. Patients were monitored for toxicity, clinical efficacy, and evidence of systemic and intraperitoneal immunologic effect. Results. Sixteen evaluable patients received a median of 4 cycles (range 1-8). No dose limiting toxicities were found. The adverse side effects were 4 grade 3 anemia, 2 grade 3 abdominal pain, 7 grade 3 neutropenia, and 2 grade 4 neutropenia. A clinical benefit of 57.1% (PR = 21.4%; SD = 35.7%) was found in the 14 patients with measurable disease. The highest number of partial responses (28.6%) and stable disease (57.1%) were found at dose level 3. The maximum tolerated dose was not reached. Increases in IL-12, IFN-gamma, and TNF-alpha levels were found in peritoneal fluid following GEN-1 treatment. Conclusions. GEN-1 in combination with PLD has encouraging clinical benefit and biological activity in recurrent or persistent EOC and warrants further investigation with escalating doses of GEN-1. (C) 2017 Elsevier Inc. All rights reserved.