A Phase I Dose-Escalation Study of E7727, an Oral Cytidine Deaminase Inhibitor (CDAi) With Oral Decitabine in Subjects With Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 35
- 试验地点
- 2
- 主要终点
- Safety and tolerability of combination cedazuridine with decitabine as assessed by number of participants who experience adverse events
研究概览
简要总结
This is a phase 1 study of the combination of cedazuridine with decitabine in patients with solid tumors. At least 6 patients will be enrolled per treatment level to assess optimal hypomethylation and toxicity (up to 35 patients total).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have advanced, unresectable, and/or metastatic solid tumor malignancy that is histologically or cytologically confirmed.
- •Patients must have received at least 2 lines of therapy in the advanced/metastatic setting (if 2 lines exist) and have no other possible therapies or refuse therapies that have shown clinical benefit for their condition.
- •ECOG performance status <1
- •Ability to understand and the willingness to sign a written informed consent document.
- •Patients must have measurable disease
- •Ability to swallow oral medications
排除标准
- •Participants who have had chemotherapy or radiotherapy within 3 weeks
- •Participants may not be receiving any other investigational agents.
- •Active hepatitis B or hepatitis C infection.
- •Active or untreated gastric or duodenal ulcer
- •Symptomatic bowel obstruction within 3 months prior to screening visit.
- •Symptomatic ascites in the last 4 weeks
- •Other protocol defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Decitabine and Cedazuridine
Treatment will be administered on an outpatient basis. Cycle length is 28 days. The dose of cedazuridine is fixed at 100mg and the dose and duration of decitabine will vary depending on when a patient enters the study.
干预措施: Decitabine (Drug)
Decitabine and Cedazuridine
Treatment will be administered on an outpatient basis. Cycle length is 28 days. The dose of cedazuridine is fixed at 100mg and the dose and duration of decitabine will vary depending on when a patient enters the study.
干预措施: Cedazuridine (Drug)
结局指标
主要结局
Safety and tolerability of combination cedazuridine with decitabine as assessed by number of participants who experience adverse events
时间窗: up to 2 years
Number of participants who have experienced grade 3 or higher adverse events, as defined by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0)
Maximum Tolerated Dose (MTD) as determined by number of participants with of dose limiting toxicities (DLT)
时间窗: up to 2 years
Maximum tolerated dose will be determined by the maximum dose at which the least number of participants experience dose-limiting toxicity. The dose limiting toxicity is defined using the Common Terminology Criteria for Adverse Events (CTCAE).
次要结局
- Pharmacokinetics of ASTX727 in solid tumor patients as measured by total exposure(Day 2)
- Pharmacokinetics of ASTX727 in solid tumor patients as measured by maximum concentration (Cmax)(Day 2)
- Objective response rate (ORR) in solid tumor patients who are treated with ASTX727(up to 2 years)
- Pharmacokinetics of ASTX727 in solid tumor patients as measured by time to maximum concentration (Tmax)(Day 2)