A Phase I/IIa Study of OTSGC-A24 Vaccine in Advanced Gastric Cancer
试验速览
- 阶段
- 1 期
- 入组人数
- 23
- 试验地点
- 5
- 主要终点
- safety of OTSGC-24
研究概览
简要总结
Active vaccination with tumor specific antigens and VEGFR1 HLA-A24 epitopes can improve survival of patients with advanced Gastric Cancer.
详细描述
Although palliative chemotherapy improved the outcome of patients with advanced Gastric Cancer, the prognosis for this group of patients remains poor. Tumor specific antigens and angiogenesis pathway are potential targets for immunotherapy. A cocktail of peptide vaccines is selected to overcome gastric cancer's heterogeneous and enhance the anti-tumor effect. Five HLA-A*2402-binding peptide vaccines derived from tumor specific antigens and VEGFR1 are chosen based on the frequencies of their expressions in gastric cancer and the ability to induce specific cytotoxic T-lymphocytes. In preclinical model, both down regulation these targets with siRNA and active vaccination resulted in tumor regression. The purpose of the study is to evaluate the safety and optimal dosing schedule of a cancer vaccine cocktail, OTSGC-A24 targeting novel specific tumor antigens FOXM1, DEPDC1, KIF20A, URLC10 and VEGFR1 in advanced gastric cancer patients with HLA-2402 haplotype.
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
- 21 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have histologically or cytologically confirmed inoperable or metastatic adenocarcinoma of the stomach or lower third of the oesophagus refractory or intolerable to standard therapy.
- •Patients must have measurable or evaluable disease.
- •Age >= 201years
- •ECOG performance status of 0 to 2
- •Life expectancy at least 3 months
- •Patients must have normal organ and marrow function as defined below:
- •absolute neutrophil count >=1,500/mcL
- •platelets >=100,000/mcL
- •total bilirubin within normal institutional limits
- •AST(SGOT)/ALT(SGPT) <=2.5 X institutional upper limit of
- •Normal creatinine within normal institutional limits
- •Patients must be HLA-A*2402
- •Patients must have recover from all reversible treatment toxicity from prior chemotherapy, radiotherapy or surgery.
- •The effects of OTSGC-A24 on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- •Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •Patients receiving any other investigational agents.
- •History of significant gastrointestinal bleeding that required intervention within the prior 1 month is ineligible; inherited bleeding diathesis or coagulopathy.
- •Serious non healing wound and peptic ulcer disease
- •Previous history of intestinal perforation
- •Invasive procedures defined as follows (Insertion of a vascular access device is not considered major/minor surgery):
- •Major surgical procedure, open biopsy or significant traumatic injury =28 days prior to -registration
- •Anticipation of need for major surgical procedures during the course of the study
- •Core biopsy <=7 days
- •Minor surgery <=2 weeks
- •Symptomatic CNS metastasis
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled hypertension (systolic >150 mmHg and/or diastolic >100 mmHg), symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction/cerebrovascular event (<=6 months prior to study entry), cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, long term systemic immunosuppressant or corticosteroid.
- •Women who are breast-feeding or pregnant are excluded from this study
结局指标
主要结局
safety of OTSGC-24
时间窗: within 4 weeks of treatment
Dose limiting toxicity will be evaluated during the first 4 weeks of treatment. If in the unlikely event that DLT is observed in 1 of the 3 subjects, an additional 3 subjects will be enrolled at the same dose level. If DLT is observed in 2 of the 6 subjects, subsequent cohorts will be treated at 0.5 mg.
Optimal dosing schedule
时间窗: 1 year
In each cohort, OTSGC-A24 (\~1 mg) will be administered subcutaneously at 3-weekly (cohort 1), 2-weekly (cohort 2) and weekly (cohort 3) interval. Treatment may continue until the subject experiences confirmed disease progression or unacceptable toxicity, withdraws consent, or requires treatment with another therapeutic modality.
次要结局
- Induction of specific cytotoxic T-lymphocyte (CTL) response(after 4 weeks and 12 weeks of vaccination)