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
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 2
- 试验地点
- 2
- 主要终点
- Number of Participants Without Grade 4 Hematological or Grade 3 to 4 Non-hematological Adverse Events
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Heterozygote or homozygote of HLA-A*02:01 allele
- •Inoperable or recurrent pancreatic cancer with or without any prior therapy
- •Difficult to continue the prior therapy due to treatment-related toxicities
- •ECOG performance status 0-2
- •Evaluable primary or metastatic lesion with RECIST v.1.0 criteria
- •Clearance period from prior therapy more than 4 weeks
- •Life expectancy more than 3 months
- •Laboratory values as follows 2,000/μL< WBC <15,000/μL Platelet count >100,000/μL AST <150 IU/L ALT <150 IU/L Total bilirubin <3.0 mg/dl Serum creatinine <3.0 mg/dl
排除标准
- •Pregnancy (refusal or inability to use effective contraceptives)
- •Breastfeeding
- •Active or uncontrolled infection
- •Systemic use of corticosteroids or immunosuppressants
- •Uncontrollable brain metastasis and/or meningeal infiltration
- •Unhealed external wound
- •Possibilities of complicated paralytic ileus or interstitial pneumonitis
- •Decision of not eligible determined by principal investigator or attending doctor
结局指标
主要结局
Number of Participants Without Grade 4 Hematological or Grade 3 to 4 Non-hematological Adverse Events
时间窗: 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)
次要结局
- Number of Participants With Tumor Regression(2 months)