A Phase I Trial Investigating Apoptosis Induction With Tumor Necrosis Factor Or Radiation Alone Prior To Intratumoral Injection Of Autologous Dendritic Cells In Patients With Locally Advanced Or Low Volume Metastatic Pancreatic Cancer.

The purpose of this trial was to determine the safety, feasibility and efficacy of intra-tumoral injection of an autologous dendritic cell (DC) based vaccine following apoptosis induction with a tumor necrosis factor expressing adenovector (TNF) or low dose radiation therapy (XRT). Methods: Between August 2006 and August 2011, 24 patients with locally advanced (n= 17) or low-volume metastatic (n=7) pancreatic cancer were enrolled to receive either: TNF on day 1 followed by vector activating XRT (2 Gy/d on days 1-3) and then an autologous, KLH pulsed DC vaccine (50M cells, day 4) for 3 weeks; or, XRT (1.9 Gy/d on days1-4) followed by DC vaccine (50M cells, day 5) for 3 weeks. Feasibility endpoints included our ability to produce the vaccine and the subject9s ability to complete all phases of the protocol. Serious adverse events (SAE) were recorded to establish safety. Efficacy was established by radiographic and biochemical tumor response, progression free (PFS) and overall survival (OS). Results: All but 2 patients completed the protocol (92%). One patient died prior to initiation of treatment (not included in survival analysis) and one disenrolled during treatment due to deep venous thrombosis. 50 of 66 (76%) total vaccines produced contained greater than 50M DC. There was no vaccine related toxicity. In the TNF group, there were 19 SAEs including one death. In the XRT group, there were 33 SAEs mostly characterized by pain, nausea, dehydration and vomiting. Two (4%) SAEs led to hospital admission, one for duodenal bleeding and one for bacteremia. Tumor response favored the radiation group as did survival. (table) Conclusions: DC based vaccines are feasible and safe in patients with advanced pancreatic cancer. Apoptosis induction using TNF, though less complicated, imparted no survival advantage over radiation alone and may have provided some disadvantage. Citation Format: Emmanuel E. Zervos, James J. Mule, Denise Brigham, William Janssen, Jennifer Cooper, Alexander S. Rosemurgy. A phase I trial investigating apoptosis induction with tumor necrosis factor or radiation alone prior to intratumoral injection of autologous dendritic cells in patients with locally advanced or low volume metastatic pancreatic cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-163. doi:10.1158/1538-7445.AM2013-LB-163