A Phase I Dose Escalation Study of JX-594 (Thymidine Kinase-deleted Vaccinia Virus Plus GM-CSF) Administered by Intravenous Infusion in Patients With Refractory Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 23
- 试验地点
- 4
- 主要终点
- Maximally-tolerated dose (MTD) and/or maximum-feasible dose (MFD) of JX-594 administered by intravenous (IV) infusion
研究概览
简要总结
This is a Phase I, open-label, dose-escalation trial in patients with advanced/metastatic solid tumors refractory to standard therapy; tumors may include malignant melanoma, non-small cell lung cancer, renal cell carcinoma, and squamous cell carcinoma of the head and neck. These tumor types were selected because evidence of biological activity was observed in these tumor types in a Phase I study of JX-594 (Pexa-Vec) administered by intratumoral injection in patients with metastatic disease to the liver. Patients will receive treatment at one of five dose levels in a sequential dose-escalating design.
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
- •Histologically-confirmed, advanced/metastatic solid tumor refractory to standard therapy or the patient has refused or does not tolerate the standard therapy; tumors may include malignant melanoma, non-small cell lung cancer, renal cell carcinoma, and squamous cell carcinoma of the head and neck
- •At least one measurable tumor mass by CT/MRI (i.e. lesion that can accurately be measured in at least one dimension with longest diameter > 1 cm)
- •At least one tumor mass amenable to biopsy and/or FNA
- •Expected survival for approximately 16 weeks or longer
- •Karnofsky Performance Score (KPS) ≥ 70
- •Age ≥18 years
- •WBC ≥ 3,500 cells/mm3 and ≤ 50,000 cells/mm3
- •ANC ≥ 1,500 cells/mm3
- •Hemoglobin ≥ 10 g/dL
- •Platelet count ≥ 100,000 plts/mm3
- •Total bilirubin ≤ 1.5 x ULN
- •AST, ALT ≤ 2.5 x ULN
- •Serum chemistries within normal limits (WNL) or Grade 1 - If patients are diabetic or have a screening random glucose > 160 mg/dL, a fasting glucose must be done and patients must be WNL or Grade 1 in order to be eligible for the study.
- •Acceptable coagulation status: INR ≤ (ULN + 10%)
- •CD4 count ≥ 500/mm3
排除标准
- •Significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication (e.g. systemic corticosteroids)
- •Known myeloproliferative disorders requiring systemic therapy
- •History of exfoliative skin condition (e.g. eczema or ectopic dermatitis) requiring systemic therapy
- •Tumor(s) invading a major vascular structure (e.g. carotid artery)
- •Tumor(s) in location that would potentially result in significant clinical adverse effects if post-treatment tumor swelling were to occur (e.g. tumors impinging on the upper airway or affecting biliary tract drainage, etc.)
- •Clinically significant and/or rapidly accumulating ascites, peri-cardial and/or pleural effusions
- •Severe or unstable cardiac disease
- •Current, known CNS malignancy (history of completely resected or irradiated brain metastases allowed)
- •Received anti-cancer therapy within 4 weeks prior to first treatment (6 weeks in case of mitomycin C or nitrosoureas)
- •Use of anti-viral, anti-platelet, or anti-coagulation medication [Patients who discontinue such medications within 7 days prior to first treatment may be eligible for this study.]
- •Pulse oximetry O2 saturation <90% at rest
- •Experienced a severe systemic reaction or side-effect as a result of a previous smallpox vaccination
- •Household contact exclusions:
- •Women who are pregnant or nursing an infant
- •Children < 5 years old
- •History of exfoliative skin condition (e.g. eczema) that at some stage has required systemic therapy
- •Significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication (e.g. systemic corticosteroids)
研究组 & 干预措施
Single Arm, dose escalation
dose escalation starting dose 1e5 pfu/kg bw to 3e7 pfu/kg bw; Recombinant Vaccinia GM-CSF (JX-594)
干预措施: Recombinant Vaccinia GM-CSF; RAC VAC GM-CSF (JX-594) (Drug)
结局指标
主要结局
Maximally-tolerated dose (MTD) and/or maximum-feasible dose (MFD) of JX-594 administered by intravenous (IV) infusion
时间窗: 4 weeks
Safety/Toxicity: Incidence of treatment-related adverse events; treatment-related serious adverse events; treatment-related Grade 3/4 toxicities; and clinically-significant, treatment-related changes from baseline in routine laboratory parameters
时间窗: 4 weeks
次要结局
- Determine the immune response to JX-594 following IV infusion(4 weeks)
- Determine the JX-594 pharmacokinetics and pharmacodynamics over time following IV infusion(4 weeks)
- Determine the delivery of JX-594 to, and concentration within, solid tumors following IV infusion(4 weeks)