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

BMC Cancer. 2012 Aug 20;12:361. doi: 10.1186/1471-2407-12-361.

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.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Antimetabolites, Antineoplastic / pharmacology
  • Antimetabolites, Antineoplastic / therapeutic use
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / immunology
  • Clinical Trials, Phase I as Topic / methods
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Deoxycytidine / therapeutic use
  • Double-Blind Method
  • Humans
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / immunology
  • Neovascularization, Pathologic / prevention & control
  • Pancreatic Neoplasms / blood supply
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / immunology*
  • Pancreatic Neoplasms / prevention & control
  • Placebos
  • Randomized Controlled Trials as Topic / methods
  • Salmonella typhi / genetics
  • Vaccines, DNA / administration & dosage*
  • Vaccines, DNA / adverse effects
  • Vaccines, DNA / immunology
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / immunology*

Substances

  • Antimetabolites, Antineoplastic
  • Cancer Vaccines
  • Placebos
  • Vaccines, DNA
  • Deoxycytidine
  • gemcitabine
  • Vascular Endothelial Growth Factor Receptor-2

Associated data

  • ISRCTN/ISRCTN68809279
  • ClinicalTrials.gov/NCT01486329