Randomized Phase Ii Trial with Dendritic Cell (Dc) Immunotherapy in Patients with Colorectal Carcinoma and Liver Metastasis Following Complete Resection and Adjuvant Chemotherapy

Abstract

ABSTRACT Background: Cellular immunotherapy with DC has well-established anti-tumor activity, as confirmed by Sipuleucel-T, the first approved treatment based in this strategy. Preclinical and clinical data indicate that efficacy of DC immunotherapy is maximized when used in the setting of minimal residual disease. Our study explores the efficacy of an autologous DC vaccine loaded with self-tumor antigens that we developed in a previous study (Alfaro, J Immunology 2011) in patients with colorectal cancer that have undergone complete resection of hepatic metastasis and standard adjuvant therapy. Trial design: In this randomized phase II study, patients with colorectal carcinoma with hepatic metastasis that have undergone standard treatment, including complete surgical resection and standard adjuvant chemotherapy, are randomized to receive DC vaccine or to observation. The two-cycle vaccination protocol includes the following strategies: a) pretreatment with cyclophosphamide to decrease regulatory T cells; b) maturation and activation of DC with TNF-alpha, interferon-alpha and poly I:C, a potent inducer of type I interferon; c) use of autologous tumor from resected liver metastasis as antigenic source, to include antigens that are exclusive of tumor cells; and d) administration of daily intradermal vaccines during four consecutive days in 2 cycles every 4 weeks. Our aim is to replicate the immune response observed during an acute viral infection in terms of activation signals and persistence of antigens in lymph nodes. The main objective is progression-free survival. Thirty-six patients will be included, allowing to detect a HR = 1.75 (alpha error = 0.2, beta error = 0.35). Secondary objectives are: safety, overall survival and immunologic response (in vitro lymphocyte responses against tumor antigens; delayed hypersensitivity reactions; induction of tumor antibody responses; DC activation parameters including IL-12 and IL-6 production and expression of CD80, CD83, CD86, B7-H1, B7-H4 and B7-DC; assessment of DC maturation by expression of pro-inflammatory cytokines; and DC migration) (ClinicalTrials.gov Identifier: NCT01348256). This abstract was accepted and previously presented at the 2014 ASCO Annual Meeting Chicago, June 2014 (TPS3129). Disclosure: All authors have declared no conflicts of interest.