NCT01986218终止1 期
Phase I Ascending Multiple-Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BMS-986115 in Subjects With Advanced Solid Tumors
Bristol-Myers Squibb2 个研究点 分布在 2 个国家目标入组 36 人开始时间: 2013年11月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- Safety and tolerability of multiple daily doses of BMS-986115
研究概览
简要总结
The primary purpose of this study is to evaluate the safety and effectiveness of daily doses of BMS-986115 in subjects with advanced solid tumors
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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 a histologically or cytologically confirmed diagnosis of solid tumors, advanced or metastatic, refractory to or relapsed from standard therapies or for which there is no known effective treatment
- •Life expectancy of at least 3 months
- •Eastern Cooperative Oncology Group (ECOG) performance status score 0-1
- •Prior anti-cancer treatments are permitted (i.e., chemotherapy, radiotherapy, hormonal, or immunotherapy)
- •At least 4 weeks must have elapsed from last dose of prior anti-cancer therapy and the initiation of study therapy
排除标准
- •Subjects with known or suspected brain metastases, primary brain tumors, or brain as the only site of disease
- •Evidence of uncontrolled, active infection, requiring systemic anti-bacterial, anti-viral or anti-fungal therapy ≤ 7 days prior to administration of study medication
- •Current or recent (within 3 months of study drug administration) gastrointestinal disease such as chronic or intermittent diarrhea, or disorders that increase the risk of diarrhea, such as inflammatory bowel disease. Non-chronic conditions (e.g. infectious diarrhea) that are completely resolved for at least 2 weeks prior to starting study treatment are not exclusionary
- •Any major surgery or gastrointestinal disease that would interfere with administration of oral medications
- •Conditions requiring chronic systemic glucocorticoid use, such as autoimmune disease or severe asthma, excluding inhalation steroids for maintenance.
- •Uncontrolled or significant cardiovascular disease
- •History of medically significant thromboembolic events or bleeding diathesis within the past 6 months
- •Inadequate bone marrow function (Absolute neutrophil count (ANC) < 1,500 cells/mm3; Platelet count < 100,000 cells/mm3; Hemoglobin < 9.0 g/dL)
- •Inadequate hepatic function (Total bilirubin > 1.5 times the institutional upper limit of normal (ULN) (except known Gilbert's syndrome); Alanine transaminase (ALT) or aspartate transaminase (AST) > 2.5 times the institutional ULN. ALT or AST up to 3 times the institutional ULN permitted if total bilirubin is normal
- •Uncontrolled (≥ Grade 2) hypertriglyceridemia (fasting triglycerides > 300 mg/dL (3.42 mmol/L))
- •Inadequate renal function (Blood creatinine > 1.5 times the institutional ULN)
- •Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or Human Immunodeficiency Virus (HIV) -1, -2 antibody
研究组 & 干预措施
Arm A: Dose Escalation (BMS-986115)
Experimental
Continuous daily dosing until disease progression or unacceptable toxicity
干预措施: BMS-986115 (Drug)
Arm A: Dose Expansion (BMS-986115)
Experimental
Continuous daily dosing until disease progression or unacceptable toxicity
干预措施: BMS-986115 (Drug)
Arm B: Dose Escalation (BMS-986115)
Experimental
Twice weekly dosing until disease progression or unacceptable toxicity
干预措施: BMS-986115 (Drug)
Arm B: Dose Expansion (BMS-986115)
Experimental
Twice weekly dosing until disease progression or unacceptable toxicity
干预措施: BMS-986115 (Drug)
结局指标
主要结局
Safety and tolerability of multiple daily doses of BMS-986115
时间窗: Up to 30 days after the last dose of study medication (approximately 18 months)
Measured by the frequency of adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, Grade 3 or 4 AEs, deaths, laboratory abnormalities and clinically relevant electrocardiogram (ECG) changes from baseline
次要结局
- Maximum observed plasma concentration (Cmax) of BMS-986115 and its active metabolite BMT-100948(29 timepoints up to Cycle 3 Day 1 (approximately 32 days))
- Area under the plasma concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-986115 and its active metabolite BMT-100948(29 timepoints up to Cycle 3 Day 1 (approximately 32 days))
- Trough observed plasma concentration (Ctrough) of BMS-986115 and its active metabolite BMT-100948(29 timepoints up to Cycle 3 Day 1 (approximately 32 days))
- Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)] of BMS-986115 and its active metabolite BMT-100948(29 timepoints up to Cycle 3 Day 1 (approximately 32 days))
- AUC Accumulation Index; ratio of AUC(TAU) at steady state to AUC(TAU) after the first dose (AI_AUC) of BMS-986115(29 timepoints up to Cycle 3 Day 1 (approximately 32 days))
- Time of maximum observed plasma concentration (Tmax) of BMS-986115 and its active metabolite BMT-100948(29 timepoints up to Cycle 3 Day 1 (approximately 32 days))
- Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-986115 and its active metabolite BMT-100948(29 timepoints up to Cycle 3 Day 1 (approximately 32 days))
- Terminal plasma half-life (T-HALF) of BMS-986115 and its active metabolite BMT-100948(29 timepoints up to Cycle 3 Day 1 (approximately 32 days))
- Apparent total body clearance (CLT/F) of BMS-986115(29 timepoints up to Cycle 3 Day 1 (approximately 32 days))
- Apparent volume of distribution at steady-state (Vz/F) of BMS-986115(29 timepoints up to Cycle 3 Day 1 (approximately 32 days))
- Ratio of metabolite AUC(INF) to parent AUC(INF) after single dose and ratio of metabolite AUC(TAU) to parent AUC(TAU) at steady state, corrected for molecular weight (MR_AUC) of BMS-986115 and its active metabolite BMT-100948(29 timepoints up to Cycle 3 Day 1 (approximately 32 days))
- Pharmacodynamics (PD) changes in the expression of Notch pathway-related genes, including but not limited to Hes1 and Deltex1, as determined by standard molecular methods(16 timepoints up to Cycle 2 Day 16 (approximately 20 days))
- Preliminary anti-tumor activity of BMS-986115 as measured by response evaluation criteria in solid tumors (RECIST)(Screening (within 30 days prior to Day 1), Every 8 weeks, End of Treatment or 30-Day follow-up visits (approximately 18 months))
研究者
研究点 (2)
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