Phase 1 Safety, Pharmacokinetic and Pharmacodynamic Study of PF-4217903 in Patients With Advanced Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
PF-04217903 may work in cancer by blocking the cell growth, migration and invasion of tumor cells. PF-04217903 is a new member in a class of drugs called c-Met/hepatocyte growth factor receptor tyrosine kinase inhibitors. This research study is the first time PF-04217903 will be given to patients. PF-04217903 is taken by mouth daily.
详细描述
The study was prematurely discontinued due to a strategic development decision by Pfizer on 10FEB2012. The decision to terminate was not based on any safety concerns.
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
- •Advanced solid tumors, histologically proven at diagnosis which is refractory to standard of care or for whom no standard of care therapy is available
- •Adequate blood cell counts, normal kidney function, and performance status of 0 or 1
排除标准
- •Major surgery, radiation therapy or anti-cancer therapy within 2 weeks of starting study treatment
- •Prior stem cell transplant
- •Active or unstable cardiac disease or heart attack within 12 months of starting study treatment
研究组 & 干预措施
1
干预措施: PF-04217903 (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: Baseline up to 21 days after the start of each increased treatment dose
MTD: dose level at which 1 of 6 participants experienced dose-limiting toxicity (DLT) after 21 days of treatment (Cycle 1). DLT: grade (Gr) 2 elevated creatinine, acute renal failure, Gr 3 thrombocytopenia with bleeding, hypertension (if unmanageable),Gr \>=3 non-hematological non-disease-related (NDR) toxicities (except alopecia,Gr 3/4 hypophosphatemia, hyperuricemia), Gr 3/4 nausea, vomiting, diarrhea, Gr 4 neutropenia, thrombocytopenia lasting for \>=7 days, febrile neutropenia, neutropenic infection, inability to deliver 80 percent of planned dose during Cycle 1 due to NDR toxicities.
Recommended Phase 2 Dose (RP2D)
时间窗: Baseline up to 21 days after the start of each increased treatment dose
Number of Participants With Dose-Limiting Toxicities (DLTs)
时间窗: Baseline up to 21 days after the start of each increased treatment dose
DLT includes Gr 2 elevated creatinine and acute renal failure, Gr 3 thrombocytopenia with bleeding, hypertension (if unmanageable), Gr \>= 3 non-hematological non-disease-related (NDR) toxicities (except alopecia, Gr 3/4 hypophosphatemia, hyperuricemia), Gr 3/4 nausea, vomiting, diarrhea, Gr 4 neutropenia, thrombocytopenia lasting for \>= 7 days, febrile neutropenia, neutropenic infection, inability to deliver at least 80 percent of planned dose during Cycle 1 due to NDR adverse events.
次要结局
- Maximum Observed Plasma Concentration (Cmax) for PF-04217903 and PF-04217903 Metabolite (PF-04328029)(0 (pre-dose), 1, 2, 4, 6, 8 and 12 hours (hrs) (just prior to evening dosing) post dose on Cycle (C) 1 Day (D) 1 and C2 D1)
- Minimum Observed Plasma Trough Concentration (Cmin) for PF-04217903 and PF-04217903 Metabolite (PF-04328029)(0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C2 D1)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-04217903 and PF-04217903 Metabolite (PF-04328029)(0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C1 D1 and C2 D1)
- Pre-dose Plasma Concentration (Ctrough) for PF-04217903 and PF-04217903 Metabolite (PF-04328029)(0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C1 D1 and C2 D1)
- Area Under the Plasma Concentration Time-curve From Zero to the Last Measured Concentration [AUC(0-last)] for PF-04217903 and PF-04217903 Metabolite (PF-04328029)(0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C1 D1 and C2 D1)
- Area Under the Curve From Time Zero to End of Dosing Interval [AUC(0-tau)] for PF-04217903 and PF-04217903 Metabolite (PF-04328029)(0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C1 D1 and C2 D1)
- Accumulation Ratio (Rac) for PF-04217903 and PF-04217903 Metabolite (PF-04328029)(0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C2 D1)
- Metabolite to Parent Ratio Area Under the Curve From Time Zero to End of Dosing Interval (MRAUCtau)(0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C1 D1 and C2 D1)
- Apparent Oral Clearance (CL/F) for PF-04217903(0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C2 D1)
- Change From Baseline in Tumor Proliferation Using F-Fluoro-3'-Deoxy-3'-L-Fluorothymidine Positron Emission Tomography (FLT-PET) Imaging at Day 1 of Cycle 2(Cycle 2 Day 1)
- Percentage of Participants With Objective Response (OR)(Baseline until disease progression up to C2 D1)