Open-label, Nonrandomized, Phase 1 Study Evaluating Safety and Pharmacokinetics of Belinostat in Patients With Relapsed/Refractory Solid Tumors or Hematological Malignancies in Wild-Type, Heterozygous, and Homozygous UGT1A1*28 Genotypes
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 3
- 主要终点
- Plasma and urine concentrations of belinostat will be measured
研究概览
简要总结
This is a Phase 1, open-label, nonrandomized study to determine the PK profiles of belinostat in patients with relapsed/refractory solid tumors or hematological malignancies who have heterozygous and homozygous UGT1A1*28 genotypes and wild-type UGT1A1 gene. Enrolled patients will be assigned to 1 of 3 cohorts (A, B, or C) based on their UGT1A1 genotype
详细描述
This is a Phase 1, open-label, nonrandomized study to determine the PK profiles of belinostat in patients with relapsed/refractory solid tumors or hematological malignancies who have heterozygous and homozygous UGT1A1*28 genotypes and wild-type UGT1A1 gene. Enrolled patients will be assigned to 1 of 3 cohorts (A, B, or C) based on their UGT1A1 genotype
Enrollment into all cohorts will occur simultaneously rather than sequentially. Belinostat will be administered via a 30-minute infusion once daily from Day 1 to Day 5 of one 21-day cycle. Clinical safety will be monitored in each patient. Blood samples for PK analysis will be collected from Day 1 to Day 3, and urine samples for PK analysis will be collected from Day 1 to Day 4.
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
- •Patient is diagnosed with advanced solid tumors or advanced hematological malignancy that is relapsed/refractory, for which no standard salvage therapy exists.
- •Patient must have received at least 1 prior systemic therapy for the current malignancy and has recovered from any toxicity of the prior therapy at screening.
- •Patient has adequate hematological and hepatic functions.
排除标准
- •Patient is taking UGT1A1 inhibitors (eg, atazanavir, gemfibrozil, indinavir, ketoconazole, sorafenib) at screening.
- •Patient has HBV or HCV
- •Patient has a known HIV positive diagnosis.
- •Patient has congestive heart failure Class III/IV
- •Patient has had previous exposure to belinostat.
研究组 & 干预措施
Wild Type UGT1A1
Cohort A: Open for Enrollment Wild Type UGT1A1, Belinostat IV
干预措施: Belinostat IV (Drug)
Heterozygous UGT1A1*28
Cohort B: Closed For Enrollment Heterozygous UGT1A1, Belinostat IV
干预措施: Belinostat IV (Drug)
Homozygous UGT1A1*28
Cohort C: Open For Enrollment Homozygous UGT1A1, Belinostat IV
干预措施: Belinostat IV (Drug)
结局指标
主要结局
Plasma and urine concentrations of belinostat will be measured
时间窗: 26 Weeks
PK will be measured for area under the time-concentration curve (AUC), steady state volume of distribution (Vdss),PK will be measured for total body clearance (CLtot),PK will be measured for fraction excreted unchanged (fe), PK will be measured for renal clearance (CLren), PK will be measured for non-renal clearance (CLnonren), PK will be measured for peak concentration (Cmax),and half-life (t1/2)
次要结局
- Assess overall incidence of treatment emergent adverse events (TEAEs) using CTCAE version 4.03(26 Weeks)
- Assess any adverse events (AEs) (changes in physical exam or laboratory findings related to study medication dosing(26 Weeks)