A Phase 1 Study to Assess the Effect of Hepatic Impairment on the Pharmacokinetics of Repotrectinib in Advanced Cancer Patients
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- Area under the plasma concentration-time curve (AUC) of repotrectinib
研究概览
简要总结
This is a Phase 1 study to evaluate the effect of moderate or severe hepatic impairment on the PK of repotrectinib in patients with advanced cancer.
详细描述
This is a Phase 1, multicenter, multiple-dose, open-label, nonrandomized study to evaluate the effect of moderate or severe hepatic impairment on the PK of repotrectinib following single and multiple dose administration of repotrectinib in patients with advanced cancer. This study will enroll 8 patients each with moderate hepatic impairment, severe hepatic impairment and normal hepatic function.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumor for which standard curative or palliative measures do not exist or are no longer effective. In case of hepatocellular carcinoma, the diagnosis should be based on at least 1 of the following:
- •The presence of at least 1 lesion, measuring ≥2 cm, with characteristic arterial enhancement and venous washout in the setting of liver cirrhosis and/or hepatitis B or C infection.
- •The presence of liver lesion(s) (as defined in inclusion criteria 3a) with alphafetoprotein ≥ 400 ng/mL.
- •Tissue confirmation.
- •For patients with genetic ROS1 or NTRK 1-3 gene fusion, tissue-based local testing should be documented.
- •Biliary obstruction for whom a biliary drain or stent has been placed are eligible.
- •Eastern Cooperative Oncology Group Performance Status scores 0 to
- •The patient must have no clinically significant change in hepatic disease status within the last 30 days before screening.
- •Patient with ascites must not have a paracentesis within 3 months of screening.
- •Protocol specified baseline hematology and kidney function laboratory values
排除标准
- •Concurrent participation in another therapeutic clinical study.
- •Symptomatic brain metastases or leptomeningeal involvement.
- •Major surgery within 4 weeks.
- •Clinically significant cardiovascular disease.
- •History of non-pharmacologically induced prolonged QT interval corrected for heart rate interval.
- •Known active infections requiring ongoing treatment (bacterial, fungal, or viral, including human immunodeficiency virus positivity).
- •Gastrointestinal disease or other malabsorption syndromes.
- •Current use or anticipated need for drugs that are known to be strong cytochrome P450 (CYP) 3A inhibitors or inducers.
研究组 & 干预措施
Repotrectinib (TPX-0005)
Oral repotrectinib (TPX-0005):
Cohort 1: Patients with moderate hepatic impairment Cohort 2: Patients with severe hepatic impairment Cohort 3: Patients with normal hepatic function
干预措施: repotrectinib (TPX-0005) (Drug)
结局指标
主要结局
Area under the plasma concentration-time curve (AUC) of repotrectinib
时间窗: Within 22 days of first repotrectinib dose
AUC0-t: Area under the plasma concentration-time curve from time 0 to the time of the last measurable concentration
Maximum Observed Plasma Concentration (Cmax) of repotrectinib
时间窗: Within 22 days of first Repotrectinib dose
Cmax: Evaluate the maximum plasma concentration
次要结局
- Evaluate safety and tolerability(28 days after last dose of repotrectinib)