Phase I, Open-Label, Multi-Center, Accelerated Dose Escalation Study Of The Anti-Angiogenesis Agent PF-00337210 In Patients 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
- 46
- 试验地点
- 1
- 主要终点
- Number of Participants With Dose-limiting Toxicities (DLTs)
研究概览
简要总结
This study will test a new cancer medication to determine if this medication will block blood supply to a tumor and decrease growth of a tumor. This study will also define the safety profile and define the safest dose of this new medication for people who have cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Histologically or cytologically confirmed advanced solid tumors un-responsive to currently available therapies or for which there is no standard therapy.
- •At least 1 measurable disease site as defined by Response Evaluation Criterion in Solid Tumors [RECIST].
- •Adequate bone marrow, liver function and renal function as defined by protocol.
- •Blood pressure Requirements During dose escalation - no evidence of pre-existing hypertension and no antihypertensive medications at baseline.
- •During dose expansion - patient's whose hypertension is controlled by antihypertensive therapy.
排除标准
- •Chemotherapy, radiotherapy or any investigational therapy within 4 weeks of study entry
- •Current use or anticipated need for drugs that are known CYP34 inhibitors or inducers.
- •Patients with carcinomatous meningitis or un-treated brain metastases.
- •Any acute cardiovascular incident within the past 12 months.
- •Patients with active gastrointestinal bleeding or significant gastrointestinal abnormalities as defined by protocol
- •Patients with no evidence of the following for 5 years: malignancy or metastatic disease of skin cancer (except melanoma), in situ cervical cancer or breast cancer or T1C prostate cancer.
研究组 & 干预措施
Cohort 1
干预措施: PF-00337210 (Drug)
Cohort 2
干预措施: PF-00337210 (Drug)
Cohort 3
干预措施: PF-00337210 (Drug)
Cohort 4
干预措施: PF-00337210 (Drug)
Cohort 5
干预措施: PF-00337210 (Drug)
Cohort 6
干预措施: PF-00337210 (Drug)
Cohort 7
干预措施: PF-00337210 (Drug)
Cohort 8
干预措施: PF-00337210 (Drug)
Cohort 9
干预措施: PF-00337210 (Drug)
Cohort 10
干预措施: PF-00337210 (Drug)
结局指标
主要结局
Number of Participants With Dose-limiting Toxicities (DLTs)
时间窗: Baseline up to Day 28
DLTs included events occurring in Cycle 1: blood pressure of 180/110 millimeters of mercury (mmHg) or higher for 3 readings over 3 hours regardless of use of anti-hypertensive drugs or greater than (\>) 160/100 mmHg for 3 readings over 3 days on maximum anti-hypertensive drugs; afebrile Grade 4 neutropenia for greater than or equal to (\>=) 7 days or \>=Grade 3 neutropenia associated with fever (1 reading of oral temperature \>38.5 degree Celsius \[degree C\] or 3 readings of oral temperature \>38.0 degree C in 24-hour period); Grade 4 thrombocytopenia; hemoptysis of \>1/2 teaspoon of bright red blood per day; proteinuria of \>=2 grams/24 hours; inability to resume PF-00337210 dosing at current dose level within 14 days of stopping due to treatment-related toxicity; \>=Grade 3 nonhematological toxicities (except alopecia and blood pressure/hypertension); Grade 3 nonhematological toxicities that could be controlled to Grade 2 or less with appropriate treatment were not considered dose limiting.
Maximum Tolerated Dose (MTD)
时间窗: Day 28
MTD: dose level at which no more than 1 of 6 participants experienced DLT during Cycle 1. DLTs: blood pressure of 180/110 mmHg or higher for 3 readings over 3 hours regardless of use of anti-hypertensive drugs or \>160/100 mmHg for 3 readings over 3 days on maximum anti-hypertensive drugs; afebrile Grade 4 neutropenia \>=7 days or \>= Grade 3 neutropenia associated with fever (1 reading of oral temperature \>38.5 degree C or 3 readings of oral temperature \>38.0 degree C in 24-hour period); Grade 4 thrombocytopenia; hemoptysis of \>1/2 teaspoon of bright red blood per day; proteinuria of \>=2 grams/24 hours; inability to resume PF-00337210 dosing at current dose level within 14 days of stopping due to treatment-related toxicity; \>=Grade 3 nonhematological toxicities (except alopecia and blood pressure/hypertension); Grade 3 nonhematological toxicities that could be controlled to Grade 2 or less with appropriate treatment were not considered dose limiting.
Maximum Administered Dose (MAD)
时间窗: Day 28
MAD: dose level at which 2 or more out of 6 participants experienced DLT during Cycle 1. DLTs: blood pressure of 180/110 mmHg or higher for 3 readings over 3 hours regardless of use of anti-hypertensive drugs or \>160/100 mmHg for 3 readings over 3 days on maximum anti-hypertensive drugs; afebrile Grade 4 neutropenia \>=7 days or \>= Grade 3 neutropenia associated with fever (1 reading of oral temperature \>38.5 degree C or 3 readings of oral temperature \>38.0 degree C in 24-hour period); Grade 4 thrombocytopenia; hemoptysis of \>1/2 teaspoon of bright red blood per day; proteinuria of \>=2 grams/24 hours; inability to resume PF-00337210 dosing at current dose level within 14 days of stopping due to treatment-related toxicity; \>=Grade 3 nonhematological toxicities (except alopecia and blood pressure/hypertension); Grade 3 nonhematological toxicities that could be controlled to Grade 2 or less with appropriate treatment were not considered dose limiting.
Recommended Phase-2 Dose (RP2D)
时间窗: Day 28
RP2D was determined based on the safety profile and pharmacodynamic findings. The twice daily dosing was preferred over once daily dosing for RP2D, as per investigator's discretion, due to more consistent changes in pharmacodynamic markers and greater clinical benefit observed in twice daily dosing.
次要结局
- Maximum Observed Plasma Concentration (Cmax)(Pre-dose,0.5,1,2,4,6,8,10,16,20,24 hours(hrs) post-dose on Day 1(0.67 mg group);pre-dose,0.5,1,2,4,6,8,18,20,24 hrs post-dose on Day 1,15,29(once daily groups);pre-dose,0.5,1,2,4,6,8 hrs post-dose on Day 1,15,29 (twice daily groups);pre-dose on Day 43, 57)
- Plasma Decay Half-Life (t1/2)(Pre-dose,0.5,1,2,4,6,8,10,16,20,24 hrs post-dose on Day 1(0.67 mg group);pre-dose,0.5,1,2,4,6,8,18,20,24 hrs post-dose on Day 1,15,29(once daily groups);pre-dose,0.5,1,2,4,6,8 hrs post-dose on Day 1,15,29 (twice daily groups);pre-dose on Day 43, 57)
- Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)](Pre-dose,0.5,1,2,4,6,8,10,16,20,24 hrs post-dose on Day 1(0.67 mg group);pre-dose,0.5,1,2,4,6,8,18,20,24 hrs post-dose on Day 1,15,29(once daily groups);pre-dose,0.5,1,2,4,6,8 hrs post-dose on Day 1,15,29 (twice daily groups);pre-dose on Day 43, 57)
- Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)](Pre-dose,0.5,1,2,4,6,8,10,16,20,24 hrs post-dose on Day 1(0.67 mg group);pre-dose,0.5,1,2,4,6,8,18,20,24 hrs post-dose on Day 1,15,29(once daily groups);pre-dose,0.5,1,2,4,6,8 hrs post-dose on Day 1,15,29 (twice daily groups);pre-dose on Day 43, 57)
- Apparent Volume of Distribution (Vss)(Pre-dose,0.5,1,2,4,6,8,10,16,20,24 hrs post-dose on Day 1(0.67 mg group);pre-dose,0.5,1,2,4,6,8,18,20,24 hrs post-dose on Day 1,15,29(once daily groups);pre-dose,0.5,1,2,4,6,8 hrs post-dose on Day 1,15,29 (twice daily groups);pre-dose on Day 43, 57)
- Systemic Clearance (CL)(Pre-dose,0.5,1,2,4,6,8,10,16,20,24 hrs post-dose on Day 1(0.67 mg group);pre-dose,0.5,1,2,4,6,8,18,20,24 hrs post-dose on Day 1,15,29(once daily groups);pre-dose,0.5,1,2,4,6,8 hrs post-dose on Day 1,15,29 (twice daily groups);pre-dose on Day 43, 57)
- Number of Participants With Objective Response of Complete Response or Partial Response(Baseline, every 8 weeks up to Cycle 25 (Week 100))
- Change From Baseline in Biomarkers at Day 1 of Each Cycle up to Cycle 25(Baseline, Day 1 of Cycle 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25)