A Phase I Study to Determine the Safety, Pharmacokinetics, and Pharmacodynamics of [GSK461364], a Polo-like Kinase 1 (PLK1) Inhibitor, in Adult Subjects With Advanced Solid Tumor or Non-Hodgkins Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Plasma levels for GSK461364 will be taken at:Schedule 1:Day 1, 8, 15, & 22 for Cycle 1 and Day 1, 8 & 15 for subsequent cycles.Schedule 2:Day 1, 2, 8, 9, 15, & 16 for all cycles.Schedule 3:Day 1 to 5 for all cycles.
研究概览
简要总结
This is a first time in human study that is being done to determine the maximum tolerated dose and initial pharmacokinetic parameters of GSK461364, given by IV, in adult subjects with solid tumors and Non-Hodgkins lymphoma.
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
- •Confirmed diagnosis of advanced solid tumor or Non-Hodgkins Lymphoma (excluding HIV-associated lymphoma) that has relapsed or is refractory to standard therapies
- •At least 18 years of age
- •Female who are of non-childbearing potential or who have a negative pregnancy test who uses approved contraception
- •Male with a female partner of childbearing potential must have had a vasectomy or both are using approved contraception
- •Lab values that are within range as described in the protocol
- •Paraffin-embedded archival tumor tissue available for testing
- •Signed written informed consent
排除标准
- •Undergone major surgery or received anti-cancer therapy
- •History of hemolytic anemia
- •Clinical lab tests that are out of range as described in the protocol
- •Females who are pregnant or lactating
- •Significant heart problems
- •Serious or unstable pre-existing medical or psychiatric condition
- •Are not able to comply with the study protocol
- •Use of prohibited medications
- •Have low blood pressure
- •Evidence of symptomatic or untreated central nervous system involvement and require corticosteroids or anti-epileptic meds
研究组 & 干预措施
Stage A
Stage A will identify maximum tolerated doses for either Schedule 1 - GSK461364 given once weekly on Day 1, 8 and 15 every 28 days; Schedule 2 - GSK 461364 given twice weekly Days 1, 2, 8, 9, 15 and 16; Schedule 3 Daily on Day 1 to Day 15 every 21 days.
干预措施: GSK461364 (Drug)
Stage B
Evaluate safety, PK, pharmacodynamic (PD) & tumor response in expanded cohorts at the MTD for at least one schedule from Stage A.
干预措施: GSK461364 (Drug)
结局指标
主要结局
Plasma levels for GSK461364 will be taken at:Schedule 1:Day 1, 8, 15, & 22 for Cycle 1 and Day 1, 8 & 15 for subsequent cycles.Schedule 2:Day 1, 2, 8, 9, 15, & 16 for all cycles.Schedule 3:Day 1 to 5 for all cycles.
时间窗: 16 Days
次要结局
- Safety will be evaluated by: - Physical exam at screen & then D1 for each cycle - 12 lead ECG & telemetry at screen & Wk 1 to 3 for Schedule 1 & 2, & Wk 1 & 2 (ECG only) for Schedule 3. - Lab tests & AE monitoring throughout the study.(16 Days)