A Phase 1 Open Label, Single Arm Trial To Evaluate The Effect Of Pf-00299804 On The Pharmacokinetics Of Dextromethorphan In Patients With Advanced Malignant Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Dextromethorphan and Dextrorphan 3 Days Prior to PF-00299804 Dosing
研究概览
简要总结
Research in test tubes suggests that may affect cytochrome P450 2D6 (CYP2D6), an important enzyme that is responsible for eliminating many drugs that cancer patients need to take, including dextromethorphan. The purpose of this study is to test the impact of PF-00299804 on the activity of CYP2D6, and how the human body handles dextromethorphan.
详细描述
To assess the effect of repeated dosing with 45 mg QD PF-00299804 on the pharmacokinetics of dextromethorphan, a CYP2D6 probe, in cancer patients with advanced malignant solid tumors.
研究设计
- 研究类型
- Interventional
- 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 histologically or cytologically confirmed advanced malignant solid tumor for which there is no currently approved treatment or which is unresponsive to currently approved therapies;
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Patients with performance status 2 could be eligible upon agreement between sponsors and investigators;
- •Adequate bone marrow, renal, liver and cardiac functions;
排除标准
- •History of Interstitial Lung Disease (ILD).
- •Drugs with known CYP2D6 inhibitory effects
- •Drugs that are highly dependent on CYP2D6 for metabolism.
- •Women who are pregnant or breastfeeding.
研究组 & 干预措施
Treatment arm
干预措施: PF-00299804 (Drug)
结局指标
主要结局
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Dextromethorphan and Dextrorphan 3 Days Prior to PF-00299804 Dosing
时间窗: Day -3: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
Area under the plasma concentration time-curve from time zero (pre-dose) to the last measured concentration (AUClast). Dextrorphan is an active metabolite of dextromethorphan.
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Dextromethorphan and Dextrorphan on Cycle 2 Day 7
时间窗: Cycle 2 Day 7: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
Area under the plasma concentration time-curve from time zero (pre-dose) to the last measured concentration (AUClast). Dextrorphan is an active metabolite of dextromethorphan.
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) For Dextrorphan 3 Days Prior to PF-00299804 Dosing
时间窗: Day -3: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf). Dextrorphan is an active metabolite of dextromethorphan.
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) For Dextrorphan on Cycle 2 Day 7
时间窗: Cycle 2 Day 7: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf). Dextrorphan is an active metabolite of dextromethorphan.
Maximum Observed Plasma Concentration (Cmax) For Dextromethorphan and Dextrorphan 3 Days Prior to PF-00299804 Dosing
时间窗: Day -3: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
Dextrorphan is an active metabolite of dextromethorphan.
Plasma Decay Half-Life (t1/2) For Dextrorphan 3 Days Prior to PF-00299804 Dosing
时间窗: Day -3: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Dextrorphan is an active metabolite of dextromethorphan.
Plasma Decay Half-Life (t1/2) For Dextrorphan on Cycle 2 Day 7
时间窗: Cycle 2 Day 7: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. Dextrorphan is an active metabolite of dextromethorphan.
Oral Clearance For Dextromethorphan 3 Days Prior to PF-00299804 Dosing
时间窗: Day -3: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Maximum Observed Plasma Concentration (Cmax) For Dextromethorphan and Dextrorphan on Cycle 2 Day 7
时间窗: Cycle 2 Day 7: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
Dextrorphan is an active metabolite of dextromethorphan.
Time to Reach Maximum Observed Plasma Concentration (Tmax) For Dextromethorphan and Dextrorphan 3 Days Prior to PF-00299804 Dosing
时间窗: Day -3: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
Dextrorphan is an active metabolite of dextromethorphan.
Time to Reach Maximum Observed Plasma Concentration (Tmax) For Dextromethorphan and Dextrorphan on Cycle 2 Day 7
时间窗: Cycle 2 Day 7: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
Dextrorphan is an active metabolite of dextromethorphan.
Oral Clearance For Dextromethorphan on Cycle 2 Day 7
时间窗: Cycle 2 Day 7: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Urinary Metabolic Ratio (UMR) of Dextromethorphan to Dextrorphan 3 Days Prior to PF-00299804 Dosing
时间窗: 8 hours after dosing on Day -3
The UMR was calculated as the ratio of the amount of dextrmotherphan excreted in urine from time zero to 8 hours post-dose on Day -3 to the amount of dextrorphan excreted in urine from time zero to 8 hours post-dose on Day -3.
Urinary Metabolic Ratio (UMR) of Dextromethorphan to Dextrorphan on Cycle 2 Day 7
时间窗: 8 hours after dosing on Day 7
The UMR was calculated as the ratio of the amount of dextrmotherphan excreted in urine from time zero to 8 hours post-dose on Day 7 to the amount of dextrorphan excreted in urine from time zero to 8 hours post-dose on Day 7.
次要结局
- Best Overall Response (BOR)(Baseline, end of every even-numbered cycle until disease progression up to end of treatment (up to 18 months))
- Duration of Response (DR)(Baseline, end of every even-numbered cycle until disease progression up to end of treatment (up to 18 months))
- Time to Tumor Progression (TTP)(Baseline, end of every even-numbered cycle until disease progression up to end of treatment (up to 18 months))