A Phase I Dose Escalation Study of NKP-1339 Administered on Days 1, 8 and 15 of Each 28-Day Cycle in Patients With Advanced Solid Tumors Refractory to Treatment
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 2
- 主要终点
- Number of participants with related adverse events
研究概览
简要总结
The purpose of this study is to determine the safety and maximal tolerated dose of NKP-1339, a ruthenium containing compound administered intravenously on a weekly schedule, in patients with advanced solid tumors. The responses to treatment in this population will be evaluated. In addition, the PD and PK properties of the compound will be explored.
详细描述
NKP-1339 is a novel GRP78 targeted ruthenium based anti-cancer compound which is intravenously administered. GRP78 is a key regulator of misfolded protein processing, which is unregulated in cancer cells. In nonclinical anti-tumor studies, NKP-1339 showed activity against many tumor types, including those resistant to platinum and other standard anti-cancer agents. This Phase I trial evaluates the safety, tolerability, maximum tolerated dose, pharmacokinetics, and pharmacodynamics of NKP-1339.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients ≥ 18 years with histologically or cytologically confirmed advanced solid tumors refractory to standard therapies who have signed an IRB approved Informed Consent Form (ICF).
- •ECOG PS 0 or
- •Adequate hematologic, hepatic and renal function
- •Minimum life expectancy ≥ 12 weeks
排除标准
- •No supplemental Iron, i.e., therapeutic or as part of a multivitamin regimen.
- •No chemotherapy, immunotherapy, or radiotherapy for < 4 weeks, BMTs < 9 months or major surgery < 3 weeks.
- •No symptomatic central nervous system metastases. No primary brain tumors or known brain metastasis unless clinically stable and on stable or reducing dose of steroids.
- •No evidence of ischemia, MI within the past 6 months, or other significant abnormality on ECG.
- •No clinically significant active infection including HIV, hepatitis B, or hepatitis C.
- •No Peripheral neuropathy ≥ Grade 2
研究组 & 干预措施
NKP-1339
NKP-1339 will be administered in single patient cohorts until ≥ Grade 2 toxicity encountered, at which time cohorts converted to a standard 3 + 3 dose escalation scheme.
When MTD is reached, an expanded cohort of up to 25 patients will be enrolled at the MTD.
干预措施: NKP-1339 (Drug)
结局指标
主要结局
Number of participants with related adverse events
时间窗: 8 weeks
The incidence and severity of related adverse events and laboratory abnormalities will be used to assess the safety and tolerability of NKP-1339.
次要结局
- Composite of pharmacokinetics(0, 0.25, 0.5, 1, 2, 4, 6, 10 and 24 hours)
- To report any responses to NKP-1339 in subjects with advanced tumors(>8 weeks)
- To explore pharmacodynamic endpoints which may be of use in the further development of NKP-1339(8 weeks)