A Phase I Study of MK-0646 in Patients With Relapsed or Refractory Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 15
- 主要终点
- Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)
研究概览
简要总结
This clinical study evaluates the safety, tolerability, pharmacokinetics, and immunogenicity of dalotuzumab (MK-0646) in participants with relapsed or refractory locally advanced or metastatic solid tumors using once weekly and once every other week dose infusion regimens.
The primary study hypothesis is that administration of dalotuzumab as a once weekly and an every other week infusion will be generally safe and well tolerated
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
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has histologically- or cytologically-confirmed metastatic or locally advanced solid tumor(s) that has (have) failed to respond to standard therapy, or for which adequate standard therapy does not exist
- •Has tumor(s) associated with insulin-like growth factor 1 receptor (IGF-1R) expression in the literature (e.g. prostate, pancreatic, colon, lung and breast)
- •Has Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
- •Demonstrates adequate organ function
排除标准
- •Has had chemotherapy, radiotherapy, or biological therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to registration
- •Is concurrently using growth hormone (GH), or growth hormone inhibitor
- •Has any active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Has any primary CNS tumor - any symptomatic ascites or plural effusion
- •Has a history or current evidence of any clinically significant disease that might confound the results of the study, complicate the interpretation of the study results, interfere with the participant's participation, or pose an additional risk to the participant
- •Is pregnant or breast-feeding
研究组 & 干预措施
Dalotuzumab 15 mg/kg/7.5 mg/kg
Participants receive an initial dose of dalotuzumab 15 mg/kg by IV infusion followed by a maintenance dose of dalotuzumab 7.5 mg/kg by IV infusion once every 2 weeks for up to 1 year or until participant withdraws consent, experiences an AE, progressive disease or major protocol violation, has moved or is lost to follow up.
干预措施: Dalotuzumab (Biological)
Dalotuzumab 10 mg/kg
Participants receive dalotuzumab 10 mg/kg by IV infusion once each week for up to 1 year or until participant withdraws consent, experiences an AE, progressive disease or major protocol violation, has moved or is lost to follow up.
干预措施: Dalotuzumab (Biological)
Dalotuzumab 5 mg/kg
Participants receive dalotuzumab 5 mg/kg by intravenous (IV) infusion once each week for up to 1 year or until participant withdraws consent, experiences an adverse event (AE), progressive disease or major protocol violation, has moved or is lost to follow up.
干预措施: Dalotuzumab (Biological)
结局指标
主要结局
Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)
时间窗: Cycle 1 (Up to 4 weeks)
Toxicity was graded and recorded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. DLTs were defined as the occurrence of any of the following events when judged to be related to the study medication: Grade 4 neutropenia; Grade 3 neutropenia with fever \>38.5°C; Grade 4 thrombocytopenia; Grade 3 or Grade 4 non-hematologic toxicity, except alopecia and inadequately treated diarrhea, nausea and vomiting. The number of participants who experienced a DLT is presented.
Number of Participants Who Experienced an Adverse Event (AE)
时间窗: Up to 30 days after last dose of study treatment (Up to 101 days)
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. Any worsening (i.e. any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE is presented.
Number of Participants Who Discontinued Study Treatment Due to an AE
时间窗: Up to 71 days
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. Any worsening (i.e. any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE is presented.
次要结局
- Apparent Terminal Half-life (t1/2) of Dalotuzumab(Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose)
- Time to Cmax (Tmax) of Dalotuzumab(Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose)
- Number of Participants Who Developed a Human Anti-Humanized Antibody (HAHA) Response to Dalotuzumab(Cycle 1: predose on Days 1, 8, 15, and 22; Cycles 2 and 3: predose on Day 1; 4 weeks after last dose of study drug)
- Maximum Plasma Concentration (Cmax) of Dalotuzumab(Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose)
- Area Under the Concentration-Time Curve From Zero to Infinity (AUC0-∞) of Dalotuzumab(Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose)
- Steady State Volume of Distribution (Vss) of Dalotuzumab(Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose)
- Clearance (CL) of Dalotuzumab(Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose)