Abstract
BackgroundPancreatic 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.MethodsThis 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.DiscussionClinical 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 registrationUniversity Hospital Medical Information Network Clinical Trials Registry, UMIN000027179. Registered on 9 April 2017.
Highlights
Pancreatic cancer is a refractory malignancy, and the development of a new effective treatment strategy is needed
We 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; the trial will be conducted only at the Second Department of Surgery at Wakayama Medical University until the safety is confirmed by interim analysis
Von Hoff et al reported the results of the MPACT trial in initially treated patients with metastatic pancreatic cancer (861 cases), in which gemcitabine plus nab-paclitaxel therapy was significantly superior to gemcitabine monotherapy in terms of response rate (23% vs 7%, p < 0.001), Progression-free survival (PFS) (5.5 months vs 3.7 months, p < 0.001), and Overall survival (OS) as the primary endpoint (8.5 months vs 6.7 months, p < 0.001) [20]
Summary
Aim The primary objective of this clinical trial is to evaluate the safety and efficacy (as measured by overall survival [OS]) of TLP0–001 in patients with pancreatic cancer. Refractory or intolerant to standard therapy through a comparison of the control group (placebo in combination with S-1 [tegafur/gimeracil/oteracil]) and the investigational product group (TLP0-001 in combination with S-1). Study setting This is an investigator-initiated, multicenter, randomized, double-blind, comparative trial. The patients are allocated to either the investigational product group or the control group in a 1:1 ratio through a central registration by dynamic allocation Study design This clinical trial will be performed in accordance with the Japanese Good Clinical Practice guidelines. The patients who meet the eligibility criteria will be randomly allocated to either the investigational product group or the control group at secondary registration. Starting the course 2 weeks after the scheduled date on the same day of the week is allowed) (b) When an adverse event that meets the dose reduction criteria of S-1 occurs after the maximum reduction, and the attending doctor judges that discontinuation of the treatment is needed (c) When the attending doctor judges that discontinuation of the treatment is needed because of adverse events other than above
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