A Two-cohort, Two-part, Phase 1, Multicenter, Open-label, Fixed-sequence, Drug-Drug Interaction and QTc Assessments of Sitravatinib Followed by Combination Treatment With Nivolumab in Patients With Advanced Solid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 3
- 主要终点
- PK parameters of probe drugs; AUC from time zero to the last data point (AUC-last)
研究概览
简要总结
Study 516-010 is an open-label Phase 1, drug-drug interaction and QTc study evaluating the effect of sitravatinib on probe substrates for CYP450 enzymes and BCRP and P-gp transporters.
详细描述
Part 1 of this study is designed to evaluate the potential for drug-drug interactions and QTc effects with sitravatinib monotherapy when administered with probe drugs for specific cytochrome P450 (CYP) enzymes (CYP2C9, CYP2D6, and CYP3A4) and P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters
Part 2 allows for patients to continue sitravatinib treatment with the addition of the checkpoint inhibitor Nivolumab.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of unresectable advanced/metastatic solid tumor
- •Life expectancy of at least 3 months
- •Adequate bone marrow and organ function
排除标准
- •Ongoing medical condition or need for treatment with medication that may affect the PK of study treatments during Part 1
- •Immunocompromising conditions
- •Impaired heart function
- •Active or prior documented autoimmune disease
研究组 & 干预措施
Phase 1, Part 1: Sitravatinib monotherapy (DDI cohort)
To evaluate the potential for drug-drug interactions (DDI) with sitravatinib monotherapy. To determine the effect of sitravatinib on the pharmacokinetics (PK) of midazolam (CYP3A4 probe substrate), warfarin (CYP2C9 probe substrate), dextromethorphan (CYP2D6 probe substrate), rosuvastatin (BCRP probe substrate), and digoxin (P-gp probe substrate).
干预措施: Sitravatinib (Drug)
Phase 1, Part 1: Sitravatinib monotherapy (DDI cohort)
To evaluate the potential for drug-drug interactions (DDI) with sitravatinib monotherapy. To determine the effect of sitravatinib on the pharmacokinetics (PK) of midazolam (CYP3A4 probe substrate), warfarin (CYP2C9 probe substrate), dextromethorphan (CYP2D6 probe substrate), rosuvastatin (BCRP probe substrate), and digoxin (P-gp probe substrate).
干预措施: Warfarin (Drug)
Phase 1, Part 1: Sitravatinib monotherapy (DDI cohort)
To evaluate the potential for drug-drug interactions (DDI) with sitravatinib monotherapy. To determine the effect of sitravatinib on the pharmacokinetics (PK) of midazolam (CYP3A4 probe substrate), warfarin (CYP2C9 probe substrate), dextromethorphan (CYP2D6 probe substrate), rosuvastatin (BCRP probe substrate), and digoxin (P-gp probe substrate).
干预措施: Dextromethorphan (Drug)
Phase 1, Part 1: Sitravatinib monotherapy (DDI cohort)
To evaluate the potential for drug-drug interactions (DDI) with sitravatinib monotherapy. To determine the effect of sitravatinib on the pharmacokinetics (PK) of midazolam (CYP3A4 probe substrate), warfarin (CYP2C9 probe substrate), dextromethorphan (CYP2D6 probe substrate), rosuvastatin (BCRP probe substrate), and digoxin (P-gp probe substrate).
干预措施: Midazolam (Drug)
Phase 1, Part 1: Sitravatinib monotherapy (DDI cohort)
To evaluate the potential for drug-drug interactions (DDI) with sitravatinib monotherapy. To determine the effect of sitravatinib on the pharmacokinetics (PK) of midazolam (CYP3A4 probe substrate), warfarin (CYP2C9 probe substrate), dextromethorphan (CYP2D6 probe substrate), rosuvastatin (BCRP probe substrate), and digoxin (P-gp probe substrate).
干预措施: Digoxin (Drug)
Phase 1, Part 1: Sitravatinib monotherapy (DDI cohort)
To evaluate the potential for drug-drug interactions (DDI) with sitravatinib monotherapy. To determine the effect of sitravatinib on the pharmacokinetics (PK) of midazolam (CYP3A4 probe substrate), warfarin (CYP2C9 probe substrate), dextromethorphan (CYP2D6 probe substrate), rosuvastatin (BCRP probe substrate), and digoxin (P-gp probe substrate).
干预措施: Rosuvastatin (Drug)
Phase 1, Part 1: Sitravatinib monotherapy (QTc cohort)
To evaluate the QTc prolongation risk for sitravatinib in patients with advanced/metastatic solid tumors via C-QTc modeling.
干预措施: Sitravatinib (Drug)
Phase 1, Part 2: Combination Therapy (both DDI and QTc cohorts)
To evaluate safety and tolerability of Sitravatinib treatment with the addition of the checkpoint inhibitor nivolumab.
干预措施: Sitravatinib (Drug)
Phase 1, Part 2: Combination Therapy (both DDI and QTc cohorts)
To evaluate safety and tolerability of Sitravatinib treatment with the addition of the checkpoint inhibitor nivolumab.
干预措施: Nivolumab (Drug)
结局指标
主要结局
PK parameters of probe drugs; AUC from time zero to the last data point (AUC-last)
时间窗: Part 1; 1-20 Days
(warfarin, dextromethorphan, midazolam, digoxin, and rosuvastatin) derived from the plasma concentration time profile before and after oral administration of sitravatinib
PK parameters of probe drugs; AUC from time zero to infinity (AUC∞)
时间窗: Part 1; 1-20 Days
(warfarin, dextromethorphan, midazolam, digoxin, and rosuvastatin) derived from the plasma concentration time profile before and after oral administration of sitravatinib
PK parameters of probe drugs; C-max
时间窗: Part 1; 1-20 Days
(warfarin, dextromethorphan, midazolam, digoxin, and rosuvastatin) derived from the plasma concentration time profile before and after oral administration of sitravatinib
Adverse Events
时间窗: Through study completion, an average of 12 months
Characterization of AEs by incidence, severity, timing, seriousness \& relationship to study treatment
次要结局
- Plasma PK parameters of sitravatinib and M10; C-max(1-20 Days)
- Plasma PK parameters of sitravatinib and M10; AUC over the dosing interval (AUC)(1-20 Days)
- Plasma PK parameters of sitravatinib and M10; trough plasma concentration (C-trough)(1-20 Days)
- Plasma PK parameters of sitravatinib and M10; time to maximum concentration (t-max)(1-20 Days)
- Adverse Events(1-20 Days)
- QT/QTc(Part 1: Pre-dose to Day 10 (QTc cohort); Part 1: Pre-dose to Day14 (DDI cohort))