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临床试验/NCT00878189
NCT00878189已完成1 期

A PHASE I TRIAL OF PF-03084014 IN PATIENTS WITH ADVANCED SOLID TUMOR MALIGNANCY AND T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA/LYMPHOBLASTIC LYMPHOMA

Pfizer10 个研究点 分布在 2 个国家目标入组 72 人开始时间: 2009年6月25日最近更新:
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适应症
干预措施
相关药物

试验速览

阶段
1 期
状态
已完成
发起方
Pfizer
入组人数
72
试验地点
10
主要终点
Number of Solid Tumor Participants With First-Cycle Dose-Limiting Toxicity (DLT)
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 phase 1, dose escalating study to determine the safety of PF-03084014 in patients with advanced cancer and leukemia

研究设计

研究类型
Interventional
分配方式
Non Randomized
主要目的
Treatment
盲法
None

入排标准

年龄范围
16 Years 至 —（Child, Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •Patients with advanced cancer that is resistant to standard therapy or for which no standard therapy is available
  • •Patients with acute T cell leukemia/lymphoblastic lymphoma that is resistant to standard therapy or for which no standard therapy is available
  • •Men and women >16 years old

排除标准

  • •Prior treatment with a gamma secretase inhibitor for treatment of cancer
  • •Patients taking Tamoxifen
  • •Patients with active graft versus host disease
  • •Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
  • •Patients who are pregnant or breast feeding
  • •Patients with clinical evidence of central nervous system disease

研究组 & 干预措施

1

Experimental

干预措施: PF-03084014 (Drug)

结局指标

主要结局

Number of Solid Tumor Participants With First-Cycle Dose-Limiting Toxicity (DLT)

时间窗: Baseline to the end of Cycle 1 (Week 4)

Any DLT event attributable to PF-03084014 during Cycle 1: non-hematologic toxicities \>= Grade 3 despite optimal care; treatment delay \>=7 days or unable to deliver at least 80% of planned dose due to treatment-related toxicities; Grade 4 neutropenia \>7 days; febrile neutropenia; neutropenic infection; Grade \>=3 thrombocytopenia with bleeding

Number of T-ALL/LBL Participants With First-Cycle DLT

时间窗: Baseline to the end of Cycle 1 (Week 4)

Any DLT attributable to PF-03084014 at 1st Cycle: non-hematologic toxicities \>= Grade 3 despite optimal care; treatment delay \>=7 days; unable to deliver at least 80% of planned dose; absolute neutrophil count (ANC) \<1000/microliter (uL), or platelet count \<30,000/uL, or hemoglobin \<8 gram/deciliter (g/dL) in a bone marrow with \<5% blasts and no evidence of leukemia or abnormal dysplasia for \>42 days

次要结局

  • AUCtau After Multiple Dose on Cycle 1 Day 21(Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose))
  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causality) by Severity (by Maximum Common Terminology Criteria for Adverse Events [CTCAE] Grade)(Baseline up to end of study (maximum of 84 months))
  • Number of Participants With TEAEs (Treatment-Related) by Severity (by Maximum CTCAE Grade)(Baseline up to end of study (maximum of 84 months))
  • Dose-normalized Cmax [Cmax (dn)] After a Single Dose on Cycle 1 Day 1(Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose))
  • Cmax After Multiple Dose on Cycle 1 Day 21(Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose))
  • Apparent Oral Clearance (CL/F) on Cycle 1 Day 21(Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose))
  • Minimum Observed Serum Concentration (Cmin) After Multiple Dose on Cycle 1 Day 21(Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose))
  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causality)(Baseline up to end of study (maximum of 84 months))
  • Number of Participants With Potentially Clinical Significant Categorical Changes From Baseline in Electrocardiogram (ECG) Findings in QTc Interval(Baseline up to end of study (maximum of 84 months))
  • Time to Reach Cmax (Tmax) After a Single Dose on Cycle 1 Day 1(Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose))
  • Average Serum Concentration (Cavg) at Steady State on Cycle 1 Day 21(Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose))
  • Maximum Observed Serum Concentration (Cmax) After a Single Dose on Cycle 1 Day 1(Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose))
  • Area Under the Time-Concentration Curve From Time 0 to the Dosing Interval (AUCtau) After a Single Dose on Cycle 1 Day 1(Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose))
  • Dose-normalized AUCtau [AUCtau (dn) ] After a Single Dose on Cycle 1 Day 1(Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose))
  • Serum Decay Half-Life (t1/2) After Multiple Dose on Cycle 1 Day 21(Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose))
  • Accumulation Ratio (Rac) on Cycle 1 Day 21(Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose), Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose))
  • AUCtau in the Fed State for Solid Tumor Participants(Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose))
  • Cmax in the Fasted State for Solid Tumor Participants(Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose))
  • Dose-normalized AUCtau [AUCtau(dn)] in the Fasted State for Solid Tumor Participants(Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose))
  • Dose-normalized Cmax [Cmax(dn)] in the Fasted State for Solid Tumor Participants(Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose))
  • Number of Participants With TEAEs (Treatment-Related)(Baseline up to end of study (maximum of 84 months))
  • AUCtau on Cycle 2 Day 1(Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose))
  • Dose-normalized Cmax [Cmax (dn)] on Cycle 2 Day 1(Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose))
  • Number of Participants With Laboratory Tests Abnormalities Meeting the Criteria of Potential Clinical Concern (Hematology and Chemistries, All Cycles)(Baseline up to end of study (maximum of 84 months))
  • Time to Reach Cmax (Tmax) After Multiple Dose on Cycle 1 Day 21(Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose))
  • Apparent Volume of Distribution (Vz/F) on Cycle 1 Day 21(Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose))
  • Dose-normalized Cmax [Cmax (dn)] After Multiple Dose on Cycle 1 Day 21(Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose))
  • AUCtau in the Fasted State for Solid Tumor Participants(Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose))
  • Cmax in the Fed State for Solid Tumor Participants(Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose))
  • Time to Tumor Progression (TTP) for Solid Tumor Participants(Baseline until first documented objective progression (up to maximum of 84 months))
  • Progression-Free Survival (PFS) for Solid Tumor Participants(Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or - 5 days) of every odd cycle or as clinically indicated, up to Cycle 9; afterwards assessed on Day 1 (+ or -5 days) every 4 cycles (up to maximum of 84 months))
  • Dose-normalized AUCtau [AUCtau (dn)] After Multiple Dose on Cycle 1 Day 21(Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose))
  • Dose-normalized AUCtau [AUCtau(dn)] in the Fed State for Solid Tumor Participants(Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose))
  • Tmax on Cycle 2 Day 1(Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose))
  • Percentage of T-ALL/LBL Participants With OR(Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or - 5 days) of every odd cycle or as clinically indicated, up to Cycle 9 (up to maximum of 84 months))
  • Changes in Expression Levels of Notch 1 Target Genes in Peripheral Blood for Solid Tumor Participants: Hes4 Gene Expression Level on Cycle 1 Day 8 and Cycle 1 Day 21 Relative to That at Baseline(Baseline (morning), Cycle 1 Days 8 and 21 (pre-dose))
  • Dose-Normalized Cmax [Cmax(dn)] in the Fed State for Solid Tumor Participants(Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose).)
  • Dose-normalized AUCtau [AUCtau (dn)] on Cycle 2 Day 1(Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose))
  • Cmax on Cycle 2 Day 1(Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose))
  • Relapse Free Survival (RFS) for T-ALL/LBL Participants(Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or - 5 days) of every odd cycle or as clinically indicated, up to Cycle 9 (up to maximum of 84 months))
  • Changes From Baseline in Notch Intracellular Domain (NICD) Levels in Bone Marrow for T-ALL/LBL Participants(Baseline, Cycle 1 Day 1 and Cycle 2 Day 1)
  • Percentage of Solid Tumor Participants With Objective Response (OR)(Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (plus [+] or minus [-] 5 days) of every odd cycle or as clinically indicated, up to Cycle 9; afterwards assessed on Day 1 (+ or -5 days) every 4 cycles)
  • Duration of Response (DR) for Solid Tumor Participants(Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or -5 days) of every odd cycle or as clinically indicated, up to Cycle 9. Afterwards, assessed on Day 1 (+ or -5 days) every 4 cycles (up to maximum of 84 months))
  • Changes in Expression Levels of Notch 1 Target Genes in Tumor Biopsies for Solid Tumor Participants: Hairy and Enhancer of Split-4 (Hes4) Gene Expression Levels on Cycle 1 Day 21 Relative to That at Baseline(Baseline, Cycle 1 Day 21 (-5 days))
  • Changes From Baseline in Notch Intracellular Domain (NICD) Levels in Peripheral Blood for T-ALL/LBL Participants(Baseline, Cycle 1 Days 8 and 15 (pre-dose AM), Cycle 1 Day 21 (pre-dose AM and 24, 48 and 120 hr post-dose) and end of treatment (EOT).)
  • Peripheral Blast Count Reduction (PBR) for T-ALL/LBL Participants(Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or - 5 days) of every odd cycle or as clinically indicated, up to Cycle 9 (up to maximum of 84 months))
  • Changes From Baseline in Expression Levels of Notch 1 Target Genes in Peripheral Blood for T-ALL/LBL Participants: Hes4 Gene Expression Levels on Cycle 1 Day 8, Cycle 1 Day 15, Cycle 1 Day 21 Relative to That at Baseline(Baseline (morning), Cycle 1 Days 8, 15 and 21 (morning, matched with the first PK sample of the particular day), Cycle 1 Day 21 (24, 48, and 120 hr post-dose) and at end of treatment (EOT))

研究者

发起方
Pfizer
申办方类型
Industry
责任方
Sponsor

研究点 (10)

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