A Phase 1, Open-Label, Dose-Ranging, Safety and Pharmacokinetic Study to Determine the Maximum Tolerated Dose of RX-3117 Administered Orally as a Single-Agent to Subjects With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 127
- 试验地点
- 1
- 主要终点
- Overall Safety Profile Characterized by # of Subjects With Dose-limiting Toxicities (DLTs) in Phase 1
研究概览
简要总结
The purpose of this study is to determine the maximum tolerated dose of RX-3117 in subjects with advanced or metastatic solid tumors (Phase 1). The purpose of the Phase 2 portion is to estimate anti-tumor activity in subjects with advanced malignancies (relapsed or refractory pancreatic or advanced bladder cancer).
详细描述
This is a dose-finding, open-label, single agent study of RX-3117. Once the maximum tolerated dose is identified additional subjects will be treated in a dose expansion followed by a 2-stage Phase 2 study. Subjects will be treated for up to 8 cycles of therapy. A cycle will be 4 weeks. RX-3117 dosing will be 3 times each week for 3 weeks follow by 1 week off treatment. All subjects will be followed for at least 30 days after the last dose of RX-3117.
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
- •Males or females who are 18 years or older
- •Able to swallow capsules
- •Histological or cytological evidence of confirmed metastatic pancreatic or advanced bladder cancer
- •Able to discontinue all anticancer therapies 2 weeks prior to study start
- •Measurable or evaluable disease using Response Evaluation Criteria in Solid Tumors
- •Life expectancy of at least 3 months
- •ECOG performance status of 0 or 1
- •Provide written informed consent
排除标准
- •Primary brain tumors or clinical evidence of active brain metastasis
- •Systemic corticosteroid use within 7 days before planned start of study therapy
- •Active infection requiring parenteral or oral antibiotics within 2 weeks before planned start of study therapy
- •Uncontrolled diabetes as assessed by the investigator
- •Prior or current history of hepatitis B, hepatitis C or human immunodeficiency virus
- •History of bone marrow of solid organ transplantation
- •History of congestive heart failure, arrhythmias, acute coronary syndrome or torsades de pointes
- •Any other medical, psychiatric, or social condition, which in the opinion of the investigator, would preclude participation in the study, pose an undue medical hazard, interfere with the conduct of the study, or interfere with interpretation of the study results
- •Known hypersensitivity to gemcitabine, azacytidine or cytosine arabinoside
- •Pregnant, planning a pregnancy or breast feeding during the study
- •Concurrent participation in another therapeutic clinical trial
研究组 & 干预措施
RX-3117
All subjects will receive RX-3117.
干预措施: RX-3117 (Drug)
结局指标
主要结局
Overall Safety Profile Characterized by # of Subjects With Dose-limiting Toxicities (DLTs) in Phase 1
时间窗: 28 days
Number of subjects participating in Phase 1 that experienced a DLT during the first cycle of treatment (28 days)
Overall Safety Profile Characterized by Number of Subjects Experiencing Serious Adverse Events in Phase 1
时间窗: through study completion, up to 224 days (8 cycles of treatment)
Number of subjects participating in Phase 1 that experience any SAEs
Progression Free Survival (Phase 2)
时间窗: 4 months
Progression Free Survival in Phase 2 of the study for pancreatic and bladder cancer subjects.
Overall Safety Profile Characterized by the Number of Subjects That Discontinue Study Treatment - Phase 1
时间窗: through study completion, up to 224 days (8 cycles of treatment)
Number of subjects participating in Phase 1 of study that discontinued study treatment due to a treatment emergent adverse event.
Overall Safety Profile Characterized by Number of Subjects Experiencing a Treatment Emergent Adverse Event- Phase 1
时间窗: through study completion, up to 224 days (8 cycles of treatment)
Number of subjects that experience any treatment-related adverse event.
次要结局
- Area Under the Plasma Concentration Time Curve (AUC) (Phase 1)(Pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 24 and 48 hours after oral administration in Cycle 1 Days 1 and 15)
- Best Overall Response Rate (Phase 2)(Baseline and at 4, 8, 12, 16 and 32 weeks)