A Phase I, Multi-center, Open-label, Drug-drug Interaction Study to Assess the Effect of TKI258 on the Pharmacokinetics of Caffeine, Diclofenac, Omeprazole and Midazolam Administered as a Four-drug Cocktail in Patients With Advanced Solid Tumors, Excluding Breast Cancer

Novartis Pharmaceuticals5 个研究点分布在 1 个国家目标入组 39 人开始时间: 2012年5月最近更新: 2020年12月21日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Novartis Pharmaceuticals
入组人数: 39
试验地点: 5
主要终点: Probe substrate pharmacokinetics (PK) parameters: Cmax (Maximum (peak) concentration of drug)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a multi-center, open-label, phase I study to assess the effects of dovitinib (TKI258) on the pharmacokinetics of a cocktail of caffeine, diclofenac, omeprazole and midazolam in patients with advanced solid tumors, excluding breast cancer. The aim of this study is to evaluate the potential effect of dovitinib (TKI258) on the metabolism of the probe drugs caffeine, diclofenac, omeprazole and midazolam, which are metabolized by CYP1A2, CYP2C9, CYP2C19 and CYP3A4 respectively (Cytochrome P450 isoenzyme), comparing the single-dose pharmacokinetics (AUCtlast, AUCinf and Cmax parameters) of each of the individual probe drug co-administered with and without multiple dose of dovitinib (TKI258) 500 mg under a 5 days on / 2 days off dose schedule. The study foresees two treatment phases: DDI (drug-drug interaction) followed by post-DDI. During the DDI phase patients receive treatment with the probe drug cocktail and dovitinib (TKI258). During the post-DDI phase patients may continue to receive treatment with dovitinib (TKI258) until disease progression (assessed by RECIST 1.1), unacceptable toxicity, death or discontinuation from the study treatment for any other reason.

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

•Patients with a cytopathologically or histopathologically confirmed diagnosis of an advanced solid tumor, excluding breast cancer which has progressed despite standard therapy or for which no standard therapy exists
•ECOG performance status 0 or 1 and anticipated life expectancy ≥ 3 months
•Patient must meet protocol-specific laboratory values

排除标准

•Patients with brain metastases
•Patients who have received or who are expected to receive any prohibited medications and therapies
•Patients who have received CYP1A2 inducer, CYP2C9/2C19 inducer or CYP3A4 inducer medications within 30 days prior to start study treatment or are expected to receive during the first 14 days after starting the study treatment
•Patients with a known hypersensitivity to benzodiazepines
•Patients who have not recovered from previous anti-cancer therapies
•Patient with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of TKI258
•Patients who have concurrent severe and/or uncontrolled concomitant medical conditions that could compromise participation in the study
•Female patients who are pregnant or breast-feeding
•Fertile males or women not willing to use highly effective methods of contraception
•Other protocol-defined inclusion/exclusion criteria will apply

研究组 & 干预措施

TKI258 (dovitinib)

Experimental

dovitinib, 5 days on / 2 days off dose schedule

干预措施: caffeine (Drug)

TKI258 (dovitinib)

Experimental

dovitinib, 5 days on / 2 days off dose schedule

干预措施: diclofenac (Drug)

TKI258 (dovitinib)

Experimental

dovitinib, 5 days on / 2 days off dose schedule

干预措施: omeprazole (Drug)

TKI258 (dovitinib)

Experimental

dovitinib, 5 days on / 2 days off dose schedule

干预措施: midazolam (Drug)

TKI258 (dovitinib)

Experimental

dovitinib, 5 days on / 2 days off dose schedule

干预措施: TKI258 (Drug)