Randomized phase II study with dendritic cell (DC) immunotherapy in patients with resected hepatic metastasis of colorectal carcinoma.

Authors

null

Javier Rodriguez

Medical Oncology, Clinica Universidad de Navarra, Pamplona, Spain

Javier Rodriguez , Ruth Vera , Fernando Pardo , Javier Herrera , Ana Chopitea , Irene Hernandez , Antonio Viudez , Carlos Garzon , Carlos Alfaro , Jose Luis Perez-Gracia , Alberto Benito , Alvaro Gonzalez , Ivan Peñuelas , Maria Rodriguez-Ruiz , Miguel F. Sanmamed , Carmen Oñate , Carmen Ochoa , Juan Pablo Fusco , Ignacio Melero

Organizations

Medical Oncology, Clinica Universidad de Navarra, Pamplona, Spain, Service of Medical Oncology, Hospital de Navarra, Pamplona, Spain, HPB Surgery, Clinica Universidad de Navarra, Pamplona, Spain, General Surgery, Complejo Hospitalario de Navarra, Pamplona, Spain, Department of Medical Oncology, Complejo Hospitalario de Navarra, Navarra Health Service, Pamplona, Spain, Complejo Hospitalario de Navarra, Medical Oncology, Pamplona, Spain, CIMA. University of Navarra, Pamplona, Spain, CUN, Department of Oncology, University of Navarra, Pamplona, Spain, Department of Radiology, Clinica Universidad de Navarra, Pamplona, Spain, Department of Biochemistry, University of Navarra, Pamplona, Spain, Department of Nuclear Medicine, Pamplona, Spain, Department of Oncology, Clinica Universidad de Navarra, Pamplona, Spain, Department of Oncology. Clinica Universidad de Navarra, Pamplona, Spain, Gene Therapy and Hepatology, Pamplona, Spain, Department of Medical Oncology, Clínica Universidad de Navarra, Pamplona, Spain, CIMA, CUN. Department of Oncology. University of Navarra, Pamplona, Spain

Research Funding

Other

Background: Cellular immunotherapy with DC is a feasible strategy with proved activity in the treatment of cancer. Preclinical and clinical data indicate that efficacy of DC immunotherapy is improved when used in clinical settings of minimal residual disease, and Sipuleucel-T is the first approved treatment based in this approach. We are exploring the efficacy of an autologous vaccine of DC loaded with self-tumor antigens that we developed in a previous pilot trial (Alfaro, J Immunology 2011) in patients with colorectal cancer with completely resected hepatic metastasis following standard adjuvant treatment. Methods: In this randomized phase II study, patients with colorectal carcinoma with hepatic metastasis treated with complete surgical resection and standard adjuvant chemotherapy are randomized to receive DC vaccine or observation. The two-cycle vaccination protocol includes the following strategies: (1) pretreatment with cyclophosphamide to decrease regulatory T cells; (2) maturation and activation of DC with TNF-alpha, interferon-alpha and poly I:C, a potent inducer of type I interferon; (3) use of autologous tumor from resected liver metastasis as antigenic source to load antigens onto DC, including antigens that are exclusive of tumor cells; and (4) administration of daily intradermal vaccines during four consecutive days in 2 cycles every 4 weeks. The strategy is to replicate the immune response induced 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 include assessment of toxicity, 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). Clinical trial information: NCT01348256.

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Abstract Details

Meeting

2014 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Developmental Therapeutics - Immunotherapy

Track

Developmental Therapeutics

Sub Track

Vaccines

Clinical Trial Registration Number

NCT01348256

Citation

J Clin Oncol 32:5s, 2014 (suppl; abstr TPS3129)

DOI

10.1200/jco.2014.32.15_suppl.tps3129

Abstract #

TPS3129

Poster Bd #

187A

Abstract Disclosures