Purpose: To assess the effects of combining the TLR agonist activity of PSK to HER-2/neu (HER2) directed monoclonal antibody therapy using a HER2 specific vaccine for the treatment of patients with advanced stage breast cancer. We will conduct pre-clinical gene-signature biomarker work in year 1 and 2 then conduct a placebo-controlled phese II randomized controlled clinical trial in years 3 and 4. Hypothesis: PSK, when added to a HER2 vaccine will improve immune response and Survival in women with advanced HER2 overexpressing breast cancer. Methods: 1) Determine whether PSK administered concurrently with HER2-targeted vaccine can enhance tumor antigen-specific immune response and prevent or delay disease progression in neu-transgenic mice; 2) Identify a gene signature that predicts clinical response in neu-transgenic mice receiving PSK, trastuzumab, and a HER2-tergeted vaccine;and 3) Determine the safety and immunogenicity of PSK as a component of combination immunotherapy in patients with advanced stage (stage IV) breast cancer. Clinical Trial Design: 30 women with advanced HER-2/neu overexpressing breast cancer who receive trastuzumab + HER2 peptide vaccine therapy will be randomized to receive PSK or placebo orally (3000 mg/day) concomitant with vaccine therapy. Primary endpoints will be intermolecular epitope spreading, changes in TGF-b serum levels and peripheral blood biomarkers identified in neu-transgenic mice as predictive of clinical response in breast cancer patients receiving HER2 ICD vaccine.

Public Health Relevance

Trametes versicolor is a immunologically active medicinal mushroom that is likely to improve the effectiveness of treatments for women with advanced breast cancer. We will investigate the effect of oral doses of PSK, a T. versicolor extract prescribed in Japan as a cancer drug, in augmenting the anticancer immune response in advanced breast cancer.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AT006028-04
Application #
8545528
Study Section
Special Emphasis Panel (ZAT1-SM)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
4
Fiscal Year
2013
Total Cost
$300,000
Indirect Cost
$40,455
Name
Bastyr University
Department
Type
DUNS #
055652309
City
Kenmore
State
WA
Country
United States
Zip Code
98028