A Phase 1, Open-label Study of the Safety, Pharmacokinetics and Efficacy of RX108 in Patients With Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- Part 2: Incidence of adverse events (AEs) and serious adverse events (SAEs).
研究概览
简要总结
RX108 is a novel, potent, small-molecule inhibitor of Na+/K+-ATPase. The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK) and efficacy of RX108 in patients with locally advanced or metastatic solid tumors.
详细描述
This is a open-label, two-part study comprised of a dose escalation part and a dose expansion part. In the dose escalation part, RX108 will be administered in ascending doses to evaluate the safety and tolerability of RX108 and determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). The dose expansion part will assess the safety, pharmacokinetics, and efficacy of RX108 at the RP2D.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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 locally advanced or metastatic cancer that has failed all systemic therapies known to confer clinical benefit
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Minimum age of 18 years
- •Adequate hematologic, hepatic and renal function
- •Written Informed Consent
- •Must agree to use adequate contraception (females and males)
排除标准
- •History of certain cardiac abnormalities
- •History of inadequate pulmonary function
- •Symptomatic brain metastasis
- •Treatment with prohibited medications
- •Known contra-indication to digoxin
- •Treatment with any unapproved therapies for cancer, or any other anti-cancer therapy within 3 weeks
- •Any toxicity related to prior treatment must have resolved to Grade 1 or less, with the exception of alopecia
- •Clinically significant active infection requiring systemic antibiotic treatment
- •Females who are pregnant or breastfeeding
研究组 & 干预措施
Dose Escalation Phase
The Dose-Escalation Phase will employ a standard 3+3 algorithm to investigate ascending dose cohorts of RX108.
干预措施: RX108 (Drug)
Dose Expansion Phase
In the Expansion Phase, subjects will receive RX108 at the maximum tolerated dose.
干预措施: RX108 (Drug)
结局指标
主要结局
Part 2: Incidence of adverse events (AEs) and serious adverse events (SAEs).
时间窗: Day 1 to 30 days post last dose
The incidence of adverse events (AEs) and serious adverse events (SAEs) for each cohort dose will be assessed using CTCAE v 5.0.
Part 1: Maximum tolerated dose (MTD) of RX108
时间窗: Day 1 to 30
All patients treated with RX108 across all dosing levels will have safety assessed in order to determine the MTD.
次要结局
- Elimination half-life (T1/2)(Day 1 and Day 3: Hours 0, 1, 2, 3, 5, 8)
- Systemic clearance (CL)(Day 1 and Day 3: Hours 0, 1, 2, 3, 5, 8)
- Area under the plasma concentration-time curve (AUC)(Day 1 and Day 3: Hours 0, 1, 2, 3, 5, 8)
- Maximum observed plasma concentration (Cmax) of RX108(Day 1 and Day 3: Hours 0, 1, 2, 3, 5, 8)
- Time to reach maximum concentration (Tmax)(Day 1 and Day 3: Hours 0, 1, 2, 3, 5, 8)
- Response rate (per RECIST v1.1)(Screening and every 2 cycles for the first 6 cycles and every 3 cycles thereafter (each cycle is 28 days), assessed up to 24 months.)