A Phase I Pharmacokinetic And Pharmacodynamic Study Of Pf-03446962 In Asian Patient With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
This is an Asian Phase 1, multi center, open label, single arm study of PF 03446962 with dose escalation and designed to define the Maximum Tolerated Dose [MTD] and the Recommended Phase 2 Dose [RP2D].
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 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 stomach cancer
- •advanced/metastasis solid tumor refractory or intolerant to established therapy
- •adequate blood chemistry, blood counts and kidney/liver function
- •willing to participate to study requirements and sign an informed consent document
排除标准
- •Chemotherapy, radiotherapy, or any investigational cancer therapy within 4 weeks of first dose of study medication
- •excessive toxicities related to prior therapies
- •pregnant or breastfeeding patients
研究组 & 干预措施
A
PF-03446962
干预措施: PF-03446962 (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: Baseline up to Week 6
The MTD was defined as the highest dose of PF-03446962 associated with the occurrence of Dose Limiting Toxicities (DLTs) in at most 1 of 6 participants with the next higher dose having at least 2/3 or 2/6 participants experiencing DLTs (that is (i.e.) Maximum Administrated Dose). DLT is defined if the participants meets the following criteria during the first 6 weeks of treatment, possibly attributable to PF-03446962. Neutropenia grade 4 (less than \[\< \])500/cubic millimeter \[mm\^ 3\]) lasting for greater than equal to (\>=) 8 days; Febrile Neutropenia \>= Grade 3; Neutropenic Infection \>= Grade 3; Grade 4 thrombocytopenia (\<25,000/mm\^3); Grade 3 thrombocytopenia (\<50,000/mm\^3) with active bleeding; Grade 3 or higher non-hematological toxicity.
Recommended Phase-2 Dose (RP2D)
时间窗: Baseline up to 28 days after last dose of study medication
RP2D was determined by a comprehensive assessments based on all the safety data, efficacy data, pharmacokinetics profile and biomarker data using blood and tumor samples.
次要结局
- Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)(Baseline up to 28 days after last dose)
- Number of Participants With Laboratory Abnormalities(Baseline up to 28 days after last dose)
- Maximum Observed Serum Concentration (Cmax)(0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1)
- Minimum Observed Serum Trough Concentration (Cmin)(0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1)
- Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)(Baseline up to 28 days after last dose)
- Number of Participants With Treatment Emergent Adverse Events (AEs) Based on Severity(Baseline up to 28 days after last dose)
- Time to Reach Maximum Observed Plasma Concentration (Tmax)(0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1)
- Area Under the Curve From Time Zero to 28 Days [AUC (0-28)](0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1)
- Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)(0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1)
- Systemic Clearance (CL)(0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1)
- Volume of Distribution (Vd)(0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1)
- Plasma Decay Half-Life (t1/2)(0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1)
- Soluble Proteins Level(Baseline, Day 1, 0 hour (H), 6 H Cycle 1 Day 1, Day 22 of Cycle 1, Day 1 Cycle 2, Day 1 Cycle 3 and end of treatment (up to cycle 30))
- Number of Participants With Human Anti-Human Antibody (HAHA)(Baseline, Post-dose (Day 1 of every Cycle up to 28 days after last dose) up to Cycle 30)
- Number of Participants With Best Overall Response (BOR)(Baseline, thereafter every 6 weeks up to end of treatment (up to Cycle 30))
- Number of Participants With Clinical Benefit Response (CBR)(Baseline, thereafter every 6 weeks up to end of treatment (up to Cycle 30))
- Progression Free Survival (PFS)(Baseline, thereafter every 6 weeks up to end of treatment (up to Cycle 30))