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Open Access Highly Accessed Study protocol

Double-blind, placebo-controlled first in human study to investigate an oral vaccine aimed to elicit an immune reaction against the VEGF-Receptor 2 in patients with stage IV and locally advanced pancreatic cancer

Andreas G Niethammer1, Heinz Lubenau1, Gerd Mikus2, Philipp Knebel3, Nicolas Hohmann2, Christine Leowardi3, Philipp Beckhove4, Mustafa Akhisaroglu4, Yingzi Ge4, Marco Springer1, Lars Grenacher5, Markus W Buchler3, Moritz Koch3, Jürgen Weitz3, Walter E Haefeli2 and Friedrich H Schmitz-Winnenthal3*

Author Affiliations

1 Vaximm, Mannheim, Germany

2 Clinical Pharmacology and Pharmacoepidemiology University of Heidelberg, Heidelberg, Germany

3 General, Visceral and Transplantation Surgery University of Heidelberg, Heidelberg, Germany

4 National Center for Tumor Disease University of Heidelberg, Heidelberg, Germany

5 Department of Diagnostic and Interventional Radiology University of Heidelberg, Heidelberg, Germany

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BMC Cancer 2012, 12:361  doi:10.1186/1471-2407-12-361

Published: 20 August 2012

Abstract

Background

The investigational oral DNA vaccine VXM01 targets the vascular endothelial growth factor receptor 2 (VEGFR-2) and uses Salmonella typhi Ty21a as a vector. The immune reaction elicited by VXM01 is expected to disrupt the tumor neovasculature and, consequently, inhibit tumor growth. VXM01 potentially combines the advantages of anti-angiogenic therapy and active immunotherapy.

Methods/Design

This phase I trial examines the safety, tolerability, and immunological and clinical responses to VXM01. The randomized, placebo-controlled, double blind dose-escalation study includes up to 45 patients with locally advanced and stage IV pancreatic cancer. The patients will receive four doses of VXM01 or placebo in addition to gemcitabine as standard of care. Doses from 106 cfu up to 1010 cfu of VXM01 will be evaluated in the study. An independent data safety monitoring board (DSMB) will be involved in the dose-escalation decisions. In addition to safety as primary endpoint, the VXM01-specific immune reaction, as well as clinical response parameters will be evaluated.

Discussion

The results of this study shall provide the first data regarding the safety and immunogenicity of the oral anti-VEGFR-2 vaccine VXM01 in cancer patients. They will also define the recommended dose for phase II and provide the basis for further clinical evaluation, which may also include additional cancer indications.

Trial registration

EudraCT No.: 2011-000222-29, NCT01486329, ISRCTN68809279

Keywords:
DNA vaccine; Oral vaccine; Pancreatic cancer; Cancer vaccine; VEGFR-2; Anti-angiogenesis