A Phase 1 Study of E7130 in Subjects With Solid Tumor
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 62
- 试验地点
- 9
- 主要终点
- Part 1: Number of participants assigned to the every 2 weeks regimen with dose-limiting toxicities (DLTs)
研究概览
简要总结
The primary objective of this study is to evaluate the tolerability and safety profile of E7130 in participants with solid tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Participants who have provided voluntary written consent for participation in this clinical study
- •Participants to whom the rules for complying with this clinical study have been adequately explained, and who intend to and can comply with these rules
- •Participants aged greater than or equal to (>=) 20 years at the time of informed consent
- •Participants with adequate function of major organs
- •Participants with Performance Status score of 0 to 1 established by the Eastern Cooperative Oncology Group (ECOG)
- •Participants who are expected to survive for 3 months or longer after starting administration of the investigational drug
- •Washout period required from the end of prior treatment to the first administration of study drug
- •Participants who agree to submit blood samples prior and during study treatment for progressive disease (PD) markers.
- •Inclusion Criteria (Part 2 only):
- •Measurable disease meeting the following criteria:
- •At least 1 lesion of >=1.0 centimeter (cm) in the longest diameter for a non-lymph node or >=1.5 cm in the short-axis diameter for a lymph node that is serially measurable according to response evaluation criteria in solid tumours (RECIST) 1.1 using computerized tomography/magnetic resonance imaging (CT/MRI).
- •Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as radiofrequency (RF) ablation must show evidence of progressive disease to be deemed a target lesion.
排除标准
- •Medical history of clinically significant cardiovascular impairment
- •Serious concomitant systemic infection requiring medical treatment (including bacterial infection and fungal infection)
- •Participants who test positive for human immunodeficiency virus (HIV antibody)
- •Active viral hepatitis (B or C) as demonstrated by positive serology or requiring treatment hepatitis B surface antigen (HBsAg), anti-hepatitis B surface antibody (anti-HBs)/hepatitis B core antibody (HBcAb) and anti-hepatitis C virus (HCV) antibody test.
- •Effusion requiring drainage
- •Participants whose toxicity of previous treatment has not recovered to Grade 1 or lower (except for alopecia and hemoglobin)
- •Other active malignancy
- •Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin [ß-hCG] or human chorionic gonadotropin [hCG]).
- •Women of childbearing potential or men of impregnate potential who don't agree that both the participant and his/her partner will use a medically effective method for contraception during the study and after study drug discontinuation (male; 90 days, female; 60 days)
- •Known intolerance to the study drug or any of the excipients
- •Any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in the study
- •Scheduled for surgery during the study
- •Diagnosed with meningeal carcinomatosis
- •Participants with brain or subdural metastases are not eligible.
研究组 & 干预措施
E7130 (3-Week Regimen)
Part 1 (Cycle 1; 21 days): On Day 1, participants will receive E7130 at (-1) a lower dose than the dose at which the first DLT was observed in the 2-week regimen. Once the MTD will be determined. Part 2: Participants with squamous cell carcinoma of the head and neck and urothelial carcinoma will be evaluated at the dose level determined in Part 1 in a 3-week or in a 2-week regimen based on the evaluations in Part 1.
干预措施: E7130 (Drug)
E7130 (2-Week Regimen)
Part 1 (Cycle 1; 28 days): The first cohort of 3 participants will receive 25 micrograms per meters squared (μg/m^2) of E7130, on Day 1 and Day 15 as an intravenous infusion. If a drug-related Grade 2 or higher toxicity excluding clinically insignificant events is not observed in the initial cohort, dose-limiting toxicities (DLTs) will be evaluated in successive dose levels with single participants until such a toxicity is observed. Once the maximum tolerated dose (MTD) will be determined. Part 2: Participants with squamous cell carcinoma of the head and neck and urothelial carcinoma will be evaluated at the dose level determined in Part 1 in a 2-week or in a 3-week regimen based on the evaluations in Part 1.
干预措施: E7130 (Drug)
结局指标
主要结局
Part 1: Number of participants assigned to the every 2 weeks regimen with dose-limiting toxicities (DLTs)
时间窗: Cycle 1 (28 days)
DLTs are defined as study drug related adverse events (AEs). Toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE 4.03).
Part 1: Number of participants assigned to the every 3 weeks regimen with DLTs
时间窗: Cycle 1 (21 days)
DLTs are defined as study drug related AEs. Toxicity will be evaluated according to NCI CTCAE 4.03.
Part 1 and Part 2: Number of participants with any clinically significant vital sign value
时间窗: Up to approximately 83 months
Clinical significance will be determined by the Investigator.
Part 1 and Part 2: Change from Baseline in body weight
时间窗: Baseline; Up to approximately 83 months
Part 1 and Part 2: Change from Baseline in the performance status (PS) score established by the Eastern Cooperative Oncology Group (ECOG)
时间窗: Baseline; Up to approximately 83 months
Part 1 and Part 2: Number of participants with adverse events (AEs)
时间窗: Up to approximately 83 months
Part 1 and Part 2: Number of participants with any clinically significant clinical laboratory test value
时间窗: Up to approximately 83 months
Clinical significance will be determined by the Investigator.
Part 1 and Part 2: Change from Baseline in arterial oxygen saturation
时间窗: Baseline; Up to approximately 83 months
Part 1 and Part 2: Number of participants with any clinically significant 12-lead electrocardiogram (ECG) value
时间窗: Up to approximately 83 months
次要结局
- Part 1 and Part 2: Recommended dose for future studies(Up to approximately 83 months)
- Part 1: Maximum Tolerated Dose (MTD) of E7130(Cycle 1 and Cycle 2 (56 days [every 2 weeks regimen] [each Cycle length = 28 days], 42 days [every 3 weeks regimen] [each Cycle length = 21 days]))
- Part 1: Area under the plasma concentration time curve (AUC) from time 0 to infinity(Bi-weekly: Cycles 1-2 Days 1 and 15: 0-168 hours post-infusion (each Cycle length=28 days); Tri-weekly: Cycles 1-2 Day 1: 0-336 hours post-infusion (each Cycle length=21 days))
- Part 1: Maximum observed plasma concentration (Cmax) of E7130(Bi-weekly: Cycles 1-2 Days 1 and 15: 0-168 hours post-infusion (each Cycle length=28 days); Tri-weekly: Cycles 1-2 Day 1: 0-336 hours post-infusion (each Cycle length=21 days))
- Part 1: Time to reach maximum plasma concentration (Tmax) of E7130(Bi-weekly: Cycles 1-2 Days 1 and 15: 0-168 hours post-infusion (each Cycle length=28 days); Tri-weekly: Cycles 1-2 Day 1: 0-336 hours post-infusion (each Cycle length=21 days))
- Part 1: Terminal elimination phase half-life (t1/2) of E7130(Bi-weekly: Cycles 1-2 Days 1 and 15: 0-168 hours post-infusion (each Cycle length=28 days); Tri-weekly: Cycles 1-2 Day 1: 0-336 hours post-infusion (each Cycle length=21 days))
- Part 1: Total clearance of E7130(Bi-weekly: Cycles 1-2 Days 1 and 15: 0-168 hours post-infusion (each Cycle length=28 days); Tri-weekly: Cycles 1-2 Day 1: 0-336 hours post-infusion (each Cycle length=21 days))
- Part 1: Volume of distribution (Vd)(Bi-weekly: Cycles 1-2 Days 1 and 15: 0-168 hours post-infusion (each Cycle length=28 days); Tri-weekly: Cycles 1-2 Day 1: 0-336 hours post-infusion (each Cycle length=21 days))
- Part 1 and Part 2: Number of participants with advanced solid tumors with anti-tumor activity(Up to approximately 83 months)
- Part 1 and Part 2: Clinical Benefit Rate (CBR)(Up to approximately 83 months)
- Part 2: Progression-free survival (PFS)(Up to approximately 83 months)
- Part 2: Overall Survival (OS)(Up to approximately 83 months)
- Part 1 and Part 2: Best Overall Response (BOR)(Up to approximately 83 months)
- Part 1 and Part 2: Objective Response Rate (ORR)(Up to approximately 83 months)
- Part 1 and Part 2: Disease Control Rate (DCR)(Up to approximately 83 months)