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.
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
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.


CONCLUSIONS
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.


BACKGROUND
EudraCT No.: 2011-000222-29, NCT01486329, ISRCTN68809279.
Vaximm, Mannheim, Germany.
Andreas G
AG
Niethammer
Heinz
H
Lubenau
Gerd
G
Mikus
Philipp
P
Knebel
Nicolas
N
Hohmann
Christine
C
Leowardi
Philipp
P
Beckhove
Mustafa
M
Akhisaroglu
Yingzi
Y
Ge
Marco
M
Springer
Lars
L
Grenacher
Markus W
MW
Buchler
Moritz
M
Koch
Jürgen
J
Weitz
Walter E
WE
Haefeli
Friedrich H
FH
Schmitz-Winnenthal
D000284:Administration, Oral; D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D017321:Clinical Trials, Phase I as Topic / Q000379:methods; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D004311:Double-Blind Method; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000276:immunology* / Q000517:prevention & control; D010919:Placebos; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012485:Salmonella typhi / Q000235:genetics; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000276:immunology*; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D019496:Cancer Vaccines; D010919:Placebos; D019444:Vaccines, DNA; D003841:Deoxycytidine; D040301:Vascular Endothelial Growth Factor Receptor-2; D000093542:Gemcitabine