A phase III, double-blind, randomized clinical trial comparing S-1 in combination with DC vaccine loaded with WT1 peptides (TLP0-001) or placebo for the patients with advanced pancreatic cancer refractory to standard chemotherapy.
ABSTRACT
Background: The development of new potent therapeutic is strongly called for treating pancreatic cancer. Dendritic cells (DCs) are a type of antigen-presenting cells that play an important role in adaptive immune system, and this property has prompted their recent application to therapeutic cancer vaccines. DCs loaded with tumor antigen ex vivo and administered as a cellular vaccine have been found to induce therapeutic anti-tumor immunity. Wilms' tumor gene WT1 is expressed in various kinds of cancers including pancreatic cancer. In pilot clinical trials of DC vaccination loaded with WT1 peptides for patients with advanced pancreatic cancer, induction of anti-tumor WT1 specific immune responses and tumor regressions have been observed (Kimura et al, Pancreas, 2012 / Kobayashi et al, Cancer Immunol Immunother, 2014 / Mayanagi et al Cancer Sci, 2015). TLP0-001 is activated Dendritic cells loaded with epitope peptides derived from WT-1.
Methods: This is an investigator initiated, phaseIII, multicenter, double-blind, randomized trial of TLP0-001+S-1 versus placebo+S-1 for the patients with locally advanced or metastatic pancreatic cancer refractory to standard chemotherapy. Patients are allocated to either DC vaccine (TLP0-001) + S-1 group or placebo + S-1 in 1:1 ratio by dynamic allocation method. The primary endpoint is overall survival. Sample size is estimated presuming the effects will be observed from the time point of 50% cumulative survival rate. Assuming a type I error alpha (two-sided) level of 5% and a power of 80% or more for hazard ratio 0.644, sample size necessary is estimated as 174 patients. When the first 6 patients are administerd TLP0-001, the independent Data Monitoring Commitee checks safety data to assess continuation of the study. Enrollment begins in March 2017.