A Phase I Dose Escalation Study of MK-8033 in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 47
- 主要终点
- Safety and tolerability of MK-8033 based on drug-related dose limiting toxicity.
研究概览
简要总结
This is a first-in-human trial to establish the safety, tolerability, Recommended Phase II Dose (RP2D), pharmacodynamic, and clinical activity of MK-8033.
Parts A and B of the study will determine the maximum tolerated dose (MTD) and RP2D. Part C of the study will be a single panel crossover study to determine the effect of omeprazole, a gastric pH modifier, on the pharmacokinetics of MK-8033.
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
- •Patient must be at least 18 years of age, with adequate organ function, and an Eastern Cooperative Oncology Group (ECOG) performance of <2
- •Patient must be willing to undergo pre-study and post-dose tumor biopsy and have tumor accessible for biopsy (Waived during Parts A and C)
排除标准
- •Patient is currently using bisphosphonate therapy or has received this therapy in past 6 months
- •Patient has had chemotherapy, radiotherapy, or biological therapy within 4 weeks of study participation
- •Patient has history of cardiac disease
- •Patient with a primary central nervous system tumor
- •Patient has a known psychiatric or substance abuse disorder
- •Patient is pregnant or breastfeeding, or expecting to conceive during the study
- •Patient is known to be Human Immunodeficiency Virus (HIV) positive and the HIV infection is not well controlled
- •Patient has received therapy with a Proton-Pump Inhibitor, Histamine2-Receptor antagonist or antacid within one week of study participation (Part B only)
结局指标
主要结局
Safety and tolerability of MK-8033 based on drug-related dose limiting toxicity.
时间窗: for the entire duration of study (27 months)
Recommended Phase II Dose (RP2D) based on safety, tumor pharmacodynamics, and pharmacokinetics
时间窗: for the entire duration of study (27 months)
Plasma area under the curve (AUC) for F2 formulation alone or in combination with omeprazole
时间窗: Day 1-21
Safety and tolerability of MK-8033 F2 formulation alone or in combination with omeprazole based on incidence of adverse experiences
时间窗: Day 1-21
Tumor Pharmacodynamics (PD): phospho-c-Met (MET or MNNG HOS Transforming gene) Levels (Parts A & B)
时间窗: Cycle 1 pre-dose & Day 12
Tumor PD: phospho-Akt (Protein Kinase B) Levels (Parts A & B)
时间窗: Cycle 1 pre-dose & Day 12
Tumor PD: phospho-MAPK (mitogen-activated protein kinase) Levels (Parts A & B)
时间窗: Cycle 1 pre-dose & Day 12
Bone PD: Cross-Linked N-telopeptides of Type I collagen (NTx) Levels (Parts A & B)
时间窗: Baseline, Cycle 1 Day 8, & Cycle 3 Day 1
次要结局
未报告次要终点