An Open-Label, Non-Randomized, Phase I Study to Assess the Absorption, Metabolism, and Excretion Following a Single Oral Dose of [14C]-Rucaparib in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Cumulative whole blood:plasma ratio calculated for AUCinf
研究概览
简要总结
The purpose of this study is to characterize the mass balance, absorption, metabolism, and elimination pathways of orally administered [14C] rucaparib followed by cycle by cycle treatment with rucaparib continuing until disease progression or other reason for discontinuation
详细描述
This is a Phase 1, open-label, non-randomized, mass balance study in patients with histologically or cytologically confirmed advanced solid tumors. Approximately 6 patients will be enrolled. The study will consist of 2 parts: a mass balance part (Part I) and a rucaparib treatment part (Part II).
Each patient will receive a single oral dose of 600 mg [14C] rucaparib (approximately 140 µCi) in the fasted state. Patients will be confined at the study site for the collection of blood samples and excreta for a maximum of 13 days, from Day -1. The patient can be discharged sooner than Day 13, if the discharge criteria are met. If the cumulative recovery of radioactivity exceeds 90% of the administered dose or if radioactivity in urine and feces is < 1% of the administered dose over a 24 hour period on two consecutive days, as determined by quick counts.
In Part II, the treatment with rucaparib in 28-day cycles will continue until progression of disease, unacceptable toxicity, or other reason for discontinuation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
盲法说明
Open Label
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 advanced solid tumor
- •Part II only: Have a known deleterious BRCA1/2 mutation (germline or somatic) as determined by a local or central laboratory
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Adequate bone marrow, renal, and liver function
排除标准
- •Prior treatment with chemotherapy, radiation, antibody therapy or other immunotherapy, gene therapy, vaccine therapy, or angiogenesis inhibitors within 14 days prior to Day 1
- •Participation in a trial involving administration of [14C]-labeled compound(s) within the last 6 months prior to Day 1
- •Arterial or venous thrombi (including cerebrovascular accident), myocardial infarction, admission for unstable angina, cardiac angioplasty, or stenting within the last 3 months prior to Screening
- •Pre-existing duodenal stent, recent or existing bowel obstruction, and/or any gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of rucaparib
- •Untreated or symptomatic central nervous system (CNS) metastases
- •Evidence or history of bleeding disorder
- •Participation in another investigational drug trial within 14 days prior to Day 1 (or 5 times the half-life of the drug, whichever is longer) or exposure to more than three new investigational agents within 12 months prior to Day 1
- •Acute illness (eg, nausea, vomiting, fever, diarrhea) within 14 days prior to Day 1, unless mild in severity and approved by the Investigator and Sponsor's/designated medical representative
- •Active second malignancy
研究组 & 干预措施
C-14 labeled rucaparib
Each patient will receive a single oral dose of 600 mg [14C] rucaparib (approximately 140 µCi) in the fasted state. Patients will be confined at the study site for the collection of blood samples and excreta for a maximum of 13 days, from Day -1. The patient can be discharged sooner than Day 13, if the discharge criteria are met.
After completion of Part I, patients with a deleterious BRCA mutation will have the option to participate in Part II by receiving 600 mg BID rucaparib tablets orally in 28 day cycles until disease progression, unacceptable toxicity, death, or discontinuation for other reasons
干预措施: C-14 labeled Rucaparib (Drug)
C-14 labeled rucaparib
Each patient will receive a single oral dose of 600 mg [14C] rucaparib (approximately 140 µCi) in the fasted state. Patients will be confined at the study site for the collection of blood samples and excreta for a maximum of 13 days, from Day -1. The patient can be discharged sooner than Day 13, if the discharge criteria are met.
After completion of Part I, patients with a deleterious BRCA mutation will have the option to participate in Part II by receiving 600 mg BID rucaparib tablets orally in 28 day cycles until disease progression, unacceptable toxicity, death, or discontinuation for other reasons
干预措施: Rucaparib (Drug)
结局指标
主要结局
Cumulative whole blood:plasma ratio calculated for AUCinf
时间窗: Day 1-13
AUC from time zero to infinity (AUCinf)
Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): Cmax
时间窗: Days 1-13
peak (maximum) concentration (Cmax)
Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): t1/2
时间窗: Days 1-13
Elimination half-life (t1/2)
Excretion rate of 14C-labeled rucaparib(radioactivity in urine)
时间窗: Days 1-13
Percent of dose excreted in urine
Excretion rate of 14C-labeled rucaparib(radioactivity in vomit, if applicable)
时间窗: Days 1-13
Percent of dose in vomit, if applicable
Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): CL/F
时间窗: Days 1-13
Oral clearance (CL/F)
Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): V/F
时间窗: Days 1-13
Apparent volume of distribution (V/F)
Pharmacokinetics of rucaparib (in urine): CLR
时间窗: Days 1-13
Renal clearance (CLR)
Excretion rate of 14C-labeled rucaparib(radioactivity in feces)
时间窗: Days 1-13
Percent of dose excreted in feces
Metabolite identification of rucaparib in plasma, urine and feces
时间窗: Days 1-13
Cumulative whole blood:plasma ratio calculated for Cmax
时间窗: Days 1-13
peak concentration (Cmax)
Cumulative whole blood:plasma ratio calculated for AUC0-tlast
时间窗: Day 1-13
AUC from time zero to the last time point with concentration above the lower limit of quantitation (AUC0-last)
Pharmacokinetics of 14C-labeled rucaparib (radioactivity in whole blood and plasma): tmax
时间窗: Days 1-13
Time to peak concentration (tmax)
Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): AUC
时间窗: Days 1-13
Area under curve (AUC)
次要结局
- Tolerability and safety of rucaparib assessed by incidence of Adverse Events (AEs), clinical laboratory abnormalities, and dose modifications(From cycle 1 Day 1 until radiologically confirmed disease progression, death, or initiation of subsequent treatment whichever comes first up to 52 weeks)