A Phase 1/2 Multiple Ascending Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BMS-863233 in Subjects With Advanced and/or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 11
- 试验地点
- 5
- 主要终点
- Number of Participants With Dose Limiting Toxicities (DLTs) of BMS-863233
研究概览
简要总结
The purpose of this study is to determine safety, tolerability and maximum tolerated dose of BMS-863233 in subjects advanced and/or Metastatic solid tumors.
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
- •Subjects with advanced and/or metastatic solid tumors who are either refractory to or have relapsed from standard therapies, or for whom a standard therapy does not exist.
- •ECOG performance status ≤ 2
- •Accessible for treatment, PK sample collection and required study follow-up
- •Total Bilirubin ≤ 1.5 x ULN and ALT, AST ≤ 2.5 x ULN
排除标准
- •Women who are pregnant or breastfeeding
- •Subjects with known or suspected brain metastasis, primary brain tumors, or brain as the only site of disease
- •Exposure to any investigational agent within 4 weeks of study drug administration
- •Subjects a history of gastrointestinal disease
研究组 & 干预措施
Cdc7-inhibitor
干预措施: Cdc7-inhibitor (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities (DLTs) of BMS-863233
时间窗: Up to 28 days
DLT is defined based on adverse events that are deemed to be drug-related and occur during the first cycle of therapy using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0.
Number of Participants With Adverse Events (AEs)
时间窗: From first dose to 30 days post last dose (Up to 14 months)
Number of participants with any grade adverse events (AEs), any grade drug-related AEs, any grade serious adverse events (SAEs), any grade drug-related SAEs, and any grade AEs leading to discontinuation of any drug. The severity of AEs will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0. An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Number of Participants Who Died
时间窗: From first dose to 30 days post last dose (Up to 14 months)
Number of participants who died due to any cause.
Number of Participants With Lab Abnormalities Grade 3-4
时间窗: From first dose to 30 days post last dose (Up to 14 months)
Number of participants with lab abnormalities grade 3-4 including hematology, chemistry, coagulation, liver and kidney function, and electrolytes using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade 3 = severe Grade 4 = very severe
次要结局
- BMS-863233 Maximum Observed Plasma Concentration (Cmax)(PK assessment include the following timepoints: predose, 0.5-, 1-, 2-, 4-, 5-, 6-, 8-hours end-of-infusion on Cycle 1 Day 1, Cycle 1 Day 14)
- BMS-863233 Time of Maximum Observed Plasma Concentration (Tmax)(PK assessment include the following timepoints: predose, 0.5-, 1-, 2-, 4-, 5-, 6-, 8-hours end-of-infusion on Cycle 1 Day 1, Cycle 1 Day 14)
- BMS-863233 Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU))(PK assessment include the following timepoints: predose, 0.5-, 1-, 2-, 4-, 5-, 6-, 8-hours end-of-infusion on Cycle 1 Day 1, Cycle 1 Day 14)
- BMS-863233 Clearance (CL)(PK assessment include the following timepoints: predose, 0.5-, 1-, 2-, 4-, 5-, 6-, 8-hours end-of-infusion on Cycle 1 Day 1, Cycle 1 Day 14)
- BMS-863233 Effective Elimination Half-Life (T-HALFeff)(PK assessment include the following timepoints: predose, 0.5-, 1-, 2-, 4-, 5-, 6-, 8-, 36-hours end-of-infusion on Cycle 1 Day 1, Cycle 1 Day 14)
- BMS-863233 Accumulation Index (AI_AUC)(PK assessment include the following timepoints: predose, 0.5-, 1-, 2-, 4-, 5-, 6-, 8-hours end-of-infusion on Cycle 1 Day 1, Cycle 1 Day 14)
- BMS-863233 Trough Observed Plasma Concentration (Ctrough)(PK assessment include the following timepoints: predose, 0.5-, 1-, 2-, 4-, 5-, 6-, 8-, 24-hours end-of-infusion on Cycle 1 Day 2 (C1D2), (C1D7, or D8, or D9), and C1D14)
- Change From Baseline in Electrocardiogram (ECG) Parameters: Mean Heart Rate(Baseline and Predose, 2-, 4-, 8-, and 24-hours post dose on Cycle 1 Day 1 (C1D1), C3D1, C4D1, C1D2, C1D15, C3D15,)
- Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval(Baseline and Predose, 2-, 4-, 8-, and 24-hours post dose on Cycle 1 Day 1 (C1D1), C1D14, C3D1, C3D15, C4D1)
- Change From Baseline in Electrocardiogram (ECG) Parameters: QRS Interval(Baseline and Predose, 2-, 4-, 8-, and 24-hours post dose on Cycle 1 Day 1 (C1D1), C1D14, C3D1, C3D15, C4D1)
- Change From Baseline in Electrocardiogram (ECG) Parameters: QTcF Interval(Baseline and Predose, 2-, 4-, 8-, and 24-hours post dose on Cycle 1 Day 1 (C1D1), C1D14, C3D1, C3D15, C4D1)
- Objective Response Rate (ORR)(From first dose up to 14 months)
- Disease Control Rate (DCR)(From first dose up to 14 months)