Human Leukocyte Antigen-A*02:01-restricted Tumor Vessel Specific Peptide Vaccination for Advanced Pancreatic Cancer
Pancreatic cancer is the fourth leading cause of cancer death in the United States, and no combination therapy is far superior to gemcitabine alone. Vascular endothelial growth factor receptor type 1 (VEGFR1) is expressed on the tumor vessels and a candidate of tumor vessel-specific peptide vaccination strategy to induce T cell immune response. We conducted the study to confirm the safety and efficacy of combined modality intervention using conventional dose of gemcitabine with peptide vaccination targeting tumor-vessel specific VEGFR1 in case of advanced/inoperable or therapy-resistant pancreatic cancer patients.
Gemcitabine 1,000 mg/m^2 (body surface area) will be administered on day 1, day 8, day 15, day 29, day 36, and day 43, respectively.
VEGFR1-derived HLA-A*02:01-restricted peptide (VEGFR1-A02-770; TLFWLLLTL) emulsified with Montanide ISA51 will be subcutaneously injected twice weekly for 8 weeks (total 16 doses).
|Pancreatic Cancer Pancreas Neoplasms||Biological: HLA-A*02:01-restricted VEGFR1-derived peptide vaccination||Phase 1 Phase 2|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase I/II Trial of Human Leukocyte Antigen (HLA)-A*02:01-restricted Vascular Endothelial Growth Factor Receptor 1 (VEGFR1)-Derived Peptide Vaccination Combined With Conventional Dose of Gemcitabine for Advanced Pancreatic Cancer|
- Number of Participants Without Grade 4 Hematological or Grade 3 to 4 Non-hematological Adverse Events [ Time Frame: 2 months ]Number of participants without grade 4 hematological or grade 3 other adverse events were caslculated based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (NCI CTCAE v.3)
- Number of Participants With Tumor Regression [ Time Frame: 2 months ]Sum of diameters of primary pancreatic tumor or metastatic tumors (target lesions) before and after vaccination were measured by computed tomography. Sum of tumors' size diameters decrease more than 30% after vaccination was diagnosed as response according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 guidelines.
|Study Start Date:||May 2008|
|Study Completion Date:||May 2009|
|Primary Completion Date:||May 2009 (Final data collection date for primary outcome measure)|
Experimental: Peptide vaccination
VEGFR1-derived HLA-A*02:01-restricted peptide (VEGFR1-A2-770; TLFWLLLTL)was vaccinated twice weekly for 8 weeks (total 16 doses) combined with conventional dose (1,000 mg/m^2 body surface area) of gemcitabine 6 doses for advanced stage pancreatic cancer to confirm the safety and efficacy of this type of peptide.
Biological: HLA-A*02:01-restricted VEGFR1-derived peptide vaccination
VEGFR1-derived HLA-A*02:01-restricted peptide (VEGFR1-A2-770; TLFWLLLTL)was vaccinated twice weekly for 8 weeks (total 16 doses) combined with conventional dose (1,000 mg/m^2 body surface area) of gemcitabine 6 doses for advanced stage pancreatic cancer to confirm the feasibility and efficacy of this type of peptide.
Other Name: VEGFR1-A2-770; TLFWLLLTL
HLA-A*02:01-restricted VEGFR1-specific cytotoxic T lymphocyte (CTL) responses were obtained from HLA-A2/Kd transgenic murine model.
HLA-A*02:01-restricted VEGFR1-specific CTL clones were also obtained from peripheral blood mononuclear cells of healthy volunteer donors.
These CTL clones showed potent anti-tumor CTL responses in HLA class Ⅰ-restricted manner in vitro.
Vaccination of HLA-A*02:01-restricted VEGFR1-specific peptide to A2/Kd transgenic mice markedly suppress the tumor-induced angiogenesis and tumor growth in vivo.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00683085
|Research Hospital, The Institute of Medical Science, The University of Tokyo|
|Minato-ku, Tokyo, Japan, 108-8639|
|Study Director:||Naohide Yamashita, MD, PhD||Director, Research Hospital, Institute of Medical Science, Tokyo University|