Phase 1 Study of Gemcitabine With Vaccine Therapy Targeting Tumor Antigen, URLC10, For The Patients With Unresectable or Recurrent Bile Duct Cancer
试验速览
- 阶段
- 1 期
- 状态
- 暂停
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Safety (toxicities as assessed by NCI CTCAE version 3)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, and immune response of different doses of URLC10 peptide emulsified with Montanide ISA51 in combination with gemcitabine. Recommended phase II dose will be also determined.
详细描述
Our previous studies have demonstrated that up-regulated lung cancer 10 (URLC10) has been identified as a new target of tumor associated antigen using cDNA microarray technique combined with the expression profiles of normal and cancer tissues. We have also found that 100% of tissue samples from bile duct cancer express URLC10. We have determined the HLA-A*2402 and HLA-A*0201 restricted epitope peptides derived from URLC10.These epitope peptides have shown to induce specific Cytotoxic T Lymphocytes (CTL). Furthermore, 60% and 20% of Japanese population have HLA-A*2402 and HLA-A*0201, respectively. Therefore, these peptides are suitable for clinical trial. On the other hand, gemcitabine is a drug approved against bile duct cancer. Recent studies has reported that gemcitabine has an additional ability to improve immune response. From these results, synergistic effect between vaccine therapy and chemotherapy using gemcitabine will be expected.
In this clinical trial, we evaluate the safety, tolerability, and immune responses of different doses of URLC10 peptide emulsified with Montanide ISA51 as immunochemotherapy in the patients with unresectable or recurrent bile duct cancer. Toxicity profiles will be monitored, and antigen specific T cell responses will be described.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS
- •Advanced bile duct cancer precluding curative surgical resection and recurrent bile duct cancer
- •measurable disease by CT scan, ultrasonography, or other imaging modalities.
- •PATIENTS CHARACTERISTICS
- •ECOG performance status 0-2
- •Life expectancy >3 months
- •Laboratory values as follows 2,000/mm³< WBC < 15,000/mm³ Platelet count ≥ 75,000/mm³ Bilirubin ≤ 1.5 x the institutional normal upper limits AST, ALT, ALP ≤ 2.5 x the institutional normal upper limits Creatinine ≤ 1.5 x the institutional normal upper limits
- •HLA-A*2402 or HLA-A*0201
- •Able and willing to give valid written informed consent
排除标准
- •Pregnancy (women of childbearing potential: Refusal or inability to use effective means of contraception)
- •Breastfeeding
- •Serious or uncontrolled infection
- •Prior chemotherapy (except gemcitabine), radiation therapy, or immunotherapy within 4 weeks.
- •Other malignancy within 5 years prior to entry into the study
- •Concomitant treatment with steroids or immunosuppressing agent
- •Disease to the central nervous system
- •Decision of unsuitableness by principal investigator or physician-in-charge
研究组 & 干预措施
Phase I study
干预措施: Peptide vaccine for URLC10 (Biological)
Phase I study
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Safety (toxicities as assessed by NCI CTCAE version 3)
时间窗: 5 years
次要结局
- DTH to URLC10 peptide(5 years)
- URLC10 peptide specific CTL induction(5 years)
- Changes in levels of regulatory T cells(5 years)
- Objective response rate as assessed by RECIST criteria(5 years)
- Time to progression(5 years)
- Survival rate(5 years)
研究者
Hiroshi Uchinami
Gastroenterological Surgery
Akita University Hospital