Journal Article

A double-blind randomized comparative clinical trial to evaluate the safety and efficacy of dendritic cell vaccine loaded with WT1 peptides (TLP0-001) in combination with S-1 in patients with advanced pancreatic cancer refractory to standard chemotherapy

Ioka, Tatsuya, Adachi, Tomohiko, Ueno, Makoto, Nagano, Hiroaki, Yamada, Suguru, Miyazawa, Motoki, Endo, Itaru, Ojima, Toshiyasu, Ohira, Masaichi, Furukawa, Masayuki, Katanuma, Akio, Yamaue, Hiroki, Sudo, Kentaro, Hara, Kazuo, Fujii, Tsutomu, Akahori, Takahiro, Kitano, Masayuki, Asahara, Shingo, Hakamada, Kenichi, Satoi, Sohei, Katsuda, Masahiro

2019

Overview

Background Pancreatic cancer is a refractory malignancy, and the development of a new effective treatment strategy is needed. We generated a dendritic cell vaccine by culturing monocytes obtained by apheresis of blood from each patient, inducing their differentiation into dendritic cells, and pulsing with tumor antigen peptides. However, the clinical efficacy of the vaccine has not been established. We therefore decided to conduct an exploratory clinical trial of dendritic cell vaccine loaded with Wilms’ tumor gene 1 peptides (TLP0-001) as a potential new treatment for patients with advanced pancreatic cancer refractory to standard chemotherapy. Methods This is an investigator-initiated, double-blind, comparative trial. The patients were allocated to two groups in a 1:1 ratio through a central registration by dynamic allocation. A total of 185 patients with inoperable or metastatic pancreatic cancer who were refractory or intolerant to standard primary chemotherapy with gemcitabine plus nab-paclitaxel will be allocated to secondary treatment either with placebo in combination with S-1 (the control group) or TLP0-001 in combination with S-1 (the investigational product group). The primary objective of this trial is to evaluate the safety and efficacy (as measured by overall survival) of the investigational product by comparing the two groups. This clinical trial will be performed in accordance with Japanese Good Clinical Practice guidelines. Discussion Clinical trials of the standard regimen, including gemcitabine, for advanced pancreatic cancer are ongoing worldwide. However, a strategy for after the primary treatment has not been established. We therefore decided to conduct this study to evaluate the safety and efficacy of TLP0-001 as a secondary treatment for pancreatic cancer in anticipation of the approval of this new drug in Japan. This trial is conducted with full consideration of safety, as it is the first-in-human clinical trial of TLP0-001; thus, the trial will be conducted only at the Second Department of Surgery at Wakayama Medical University until the safety is confirmed by interim analysis. We plan to conduct a multicenter trial at 18 institutions in Japan after confirmation of the safety. Trial registration University Hospital Medical Information Network Clinical Trials Registry, UMIN000027179 . Registered on 9 April 2017.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adult / Aged / Antigens / Apheresis / Biomedicine / Cancer metastasis / Cancer therapies / Cancer treatment / Cancer Vaccines - adverse effects / Cancer Vaccines - therapeutic use / Carcinoma, Pancreatic Ductal - immunology / Carcinoma, Pancreatic Ductal - mortality / Carcinoma, Pancreatic Ductal - pathology / Carcinoma, Pancreatic Ductal - therapy / Chemotherapy / Clinical practice guidelines / Clinical trials / Comparative analysis / Dendritic cells / Dendritic Cells - immunology / Dendritic Cells - transplantation / Double-Blind Method / Double-blind studies / Drug approval / Drug Combinations / Drug dosages / Drug Resistance, Neoplasm / Drug therapy / Female / Genes / Health Sciences / Humans / Immunotherapy / Japan / Male / Medical prognosis / Medical schools / Medicine / Medicine & Public Health / Middle Aged / Multicenter Studies as Topic / Oxonic Acid - adverse effects / Oxonic Acid - therapeutic use / Pancreatic cancer / Pancreatic Neoplasms - immunology / Pancreatic Neoplasms - mortality / Pancreatic Neoplasms - pathology / Pancreatic Neoplasms - therapy / Patients / Peptide Fragments - immunology / Peptides / Pleural effusion / Product development / Randomized Controlled Trials as Topic / Registration / S-1 / Statistics for Life Sciences / Study Protocol / Surgery / Tegafur - adverse effects / Tegafur - therapeutic use / Time Factors / Treatment Outcome / Tumors / Vaccine / Vaccines / Wilms’ tumor gene 1 / WT1 Proteins - immunology / Young Adult