A Phase 1, Multicenter, Open-label, Dose-escalation, Safety, Pharmacokinetic, And Pharmacodynamic Study Of Cvx-241, A Selective Angiopoietin-2 And Vascular Endothelial Growth Factor Binding, Anti-angiogenic Covx-body, In Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 31
- 试验地点
- 3
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
The purpose of this study is to determine if CVX-241 (PF-05057459) is safe and tolerable when given as weekly infusions to adult patients with advanced solid tumors.
详细描述
The study was prematurely discontinued on 14 September 2011 due to no significant pharmacological effects (safety/PD/efficacy) through 25 mg/kg cohort, the T1/2 based on VEGF binding was shorter than expected and the current and/or higher doses were not considered feasible for further development. There were no safety concerns associated with the decision to terminate the program/study.
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
- 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
- •Confirmed solid tumors unresponsive to current therapy or for which there is no standard therapy.
- •Stage 2 only: Histologically or cytologically documented EOC or PPC with < or equal to 3 previous anti-cancer therapies, but at least 1 prior platinum containing regimen.
- •Adequate coagulation, liver, and renal function.
- •Candidate for Dynamic Contrast-Enhanced Magnetic Resonance Imaging [DCE-MRI] evaluation
- •Eastern Cooperative Oncology Group [ECOG] performance status of 0 or 1
排除标准
- •History of clinically significant toxicity to Vascular Endothelial Growth Factor [VEGF] inhibition.
- •Evidence of bleeding problems.
- •Uncontrolled hypertension.
- •Patients with primary brain cancer and/or non-small cell lung cancer of squamous cell histology
研究组 & 干预措施
Active Drug
Weekly infusions of CVX-241 at specified doses
干预措施: CVX-241 (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: Stage 1: Baseline up to Day 28 (end of cycle 1)
MTD was defined as highest dose level for which no more than 1 participant in a dose cohort experienced dose limiting toxicity (DLT). DLT was defined as any of the following events occurring during the first 28 days of study medication and considered at least possibly-related to study medication: any grade 3 or 4 clinically-relevant non-hematologic toxicity, any clinically-significant grade 2 non-hematologic toxicity that requires 14 days to resolve (to grade 1).
Recommended Phase 2 Dose (RP2D)
时间窗: Stage 1: Baseline up to Day 28 (end of cycle 1)
RP2D was the highest dose where 0 of 3 or less than (\<2) out of 6 participants experience a DLT. DLT was defined as any of the following events occurring during the first 28 days of study medication and considered at least possibly-related to study medication: any grade 3 or 4 clinically-relevant non-hematologic toxicity, any clinically-significant grade 2 non-hematologic toxicity that requires 14 days to resolve (to grade 1).
次要结局
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs)(Baseline up to 28 days after last dose of study medication (last dose = up to Cycle 39))
- Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUCinf](Pre-dose, 1, 2, 4, 6 hours post dose at Day 1 of cycle 1)
- Number of Participants With Dose Limiting Toxicities (DLTs)(Stage 1: Baseline up to Week 4)
- Maximum Observed Plasma Concentration (Cmax)(Pre-dose, 1, 2, 4, 6 hours post dose at Day 1, Day 22 of cycle 1)
- Minimum Observed Plasma Trough Concentration (Cmin)(Pre-dose, 1, 2, 4, 6 hours post dose at Day 1, Day 22 of cycle 1)
- Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentrations(Cycle 1/Day 1, Cycle 1/Day 5, Cycle 1/Day 8, Cycle 1/Day 15, Cycle 1/Day 22, Cycle 2/Day 1)
- Participants WithTumor Response of CA-125 Epithelial Ovarian Cancer (EOC)/ Primary Peritoneal Cancer (PPC)(Stage 2 every cycle)
- Systemic Clearance (CL)(Pre-dose, 1, 2, 4, 6 hours post dose at Day 1, Day 22 of cycle 1)
- Plasma Decay Half-Life (t1/2)(Pre-dose, 1, 2, 4, 6 hours post dose at Day 1 of cycle 1)
- Change From Baseline in Serum Angiopoietin-2 (Ang2) Concentrations(Cycle 1/Day 1, Cycle 1/Day 5, Cycle 1/Day 8, Cycle 1/Day 15, Cycle 1/Day 22, Cycle 2/Day 1)
- Objective Response Rate - Percentage of Participants With Objective Response(Every 8 weeks from start of treatment until last dose of study medication (last dose = up to Cycle 39))
- Participants With Reduction in Tumor Vascular Permeability: Blood Flow and Blood Volume as Measured by Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI)(Stage 2 predose up to end of study)
- Number of Anti Drug Antibody Samples With Positive Anti-CVX-241 Antibodies(Day 1 pre-dose of each cycle up to last dose of study medication (last dose = up to Cycle 39))