Phase 1 Clinical Study for Evaluating the Safety and Efficacy of a Transdermal Injection of JX-594 (Thymidine Kinase (-)/GM-CSF(+) Vaccinia Virus) Within the Tumor of Patients With Hepatic Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 14
- 试验地点
- 2
- 主要终点
- To determine the maximum tolerable dose (MTD) and/or the maximum feasible dose (MFD), as well as to evaluate the safety of JX-594 injected within unresectable solid tumor(s) within the liver
研究概览
简要总结
The primary purpose of this study is to determine the maximum tolerable dose (MTD) and/or the maximum feasible dose (MFD), as well as to evaluate the safety of JX-594 (Pexa-Vec) injected within hepatic carcinoma tumors.
详细描述
Patients are treated with JX-594 once every three weeks until progression at the site(s) of injection or until the patient has received a maximum of 4 treatments; four additional cycles can be administered to patients with an objective response of the injected tumor(s) (i.e. 8 total treatments possible). Study dose levels are 1e8 pfu, 3e8 pfu, 1e9 pfu and 3e9 pfu per treatment. Standard Phase I dose-escalation guidelines are used, with 2-6 patients enrolled per cohort (3 if no dose-limiting toxicities are reported).
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Patients with hepatic carcinoma (primary or metastatic) clinically or histologically confirmed to have tumors (≤10cm maximum diameter) that are progressing (refractory to standard treatment) despite regular treatment and that can be transdermally accessed by an injection needle in an imaging-guided procedure
- •Tumor progression despite undergoing regular treatment such as surgery, transarterial chemoembolization, chemotherapy, and radiotherapy
- •Performance score: Karnofsky Performance Score (KPS) ≥70
- •Expected survival of at least 16 weeks
- •For patients who are sexually active, able and willing to use contraceptives for a three month period during and after taking JX-594
- •WBC > 3,500 cells/mm3
- •ANC > 1,500 cells/mm3
- •Hemoglobin > 10g/dL
- •Platelet count > 75,000 plts/mm3
- •Serum creatinine < 1.5 mg/dL
- •AST, ALT < 2.5 x ULN
- •Total bilirubin ≤ 2.0 mg/dL
- •In patients with primary HCC, Child Pugh A or B
- •Able/willing to sign an IRB/IEC/REB-approved written consent form
- •Able and willing to comply with study procedures and follow-up examinations
排除标准
- •Pregnant or nursing an infant
- •Known infection with HIV
- •Clinically significant active infection or uncontrolled medical condition considered high risk for investigational new drug treatment
- •Significant immunodeficiency due to underlying illness (e.g. hematological malignancies, congenital immunodeficiencies and/or HIV infection/AIDS) and/or medication (e.g. high-dose systemic corticosteroids)
- •Patients with household contacts with significant immunodeficiency
- •History of exfoliative skin condition (e.g. severe eczema, ectopic dermatitis, or similar skin disorder) that at some stage has required systemic therapy
- •Severe or unstable cardiac disease
- •Use of adrenal cortical hormone drug or immunosuppressant within four weeks of study enrollment
研究组 & 干预措施
1
1e8 pfu (plaque forming units)total dose each treatment day
干预措施: JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF) (Genetic)
2
3e8 pfu (plaque forming units) total dose each treatment day
干预措施: JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF) (Genetic)
3
1e9 pfu (plaque forming units) total dose each treatment day
干预措施: JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF) (Genetic)
4
3e9 pfu (plaque forming units) total dose each treatment day
干预措施: JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF) (Genetic)
结局指标
主要结局
To determine the maximum tolerable dose (MTD) and/or the maximum feasible dose (MFD), as well as to evaluate the safety of JX-594 injected within unresectable solid tumor(s) within the liver
时间窗: Safety evaluation throughout study participation
次要结局
- Secondary objectives include determination of JX-594 pharmacokinetics, replication and shedding, immune response, and injection site tumor responses.
- Secondary objectives include determination of JX-594 pharmacokinetics, replication and shedding, immune response, and injection site tumor responses.(Throughout the study participation, up to 1 year post-treatment)