A Phase I Study of Pazopanib as a Single Agent for Children With Relapsed or Refractory Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 55
- 试验地点
- 14
- 主要终点
- Maximum-tolerated dose of pazopanib hydrochloride defined as the maximum dose at which fewer that one-third of patients experience DLT
研究概览
简要总结
This phase I trial is studying the side effects and best dose of pazopanib hydrochloride in treating young patients with solid tumors that have relapsed or not responded to treatment. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
详细描述
PRIMARY OBJECTIVES:
I. Estimate the maximum-tolerated dose and/or recommended phase II dose of pazopanib hydrochloride in pediatric patients with relapsed or refractory solid tumors.
II. Define and describe the toxicities of this regimen in these patients. III. Characterize the pharmacokinetics of pazopanib hydrochloride in these patients.
SECONDARY OBJECTIVES:
I. Preliminarily define the antitumor activity of pazopanib hydrochloride within the confines of a phase I study.
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
- 2 Years 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of 1 of the following:
- •NOTE: Histologic confirmation not required for intrinsic brain stem cell tumor, optic pathway gliomas, pineal tumors and elevations of cerebrospinal fluid, and serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin.
- •Histologically confirmed relapsed or refractory solid tumors at original diagnosis including CNS tumors* (Part 1 and Part 2a)
- •Neurologic deficits in patients with CNS tumors must have been relatively stable for ≥ 1 week
- •Histologically confirmed soft tissue sarcoma, desmoplastic small round cell tumor, or extraosseus Ewing sarcoma at original diagnosis including the following (Part 2b):
- •Tumor in the head, neck, or extremity or fixed within the abdomen or pelvis that it is not sensitive to motion artifact
- •No isolated pulmonary metastases
- •Disease with no known curative therapy or no therapy proven to prolong survival with acceptable quality of life
- •Measurable or evaluable disease (Part 1 and Part 2a)
- •Measurable tumor that is ≥ 2 cm in its longest diameter (Part 2b)
- •Patients must be:
- •> 2 years of age and ≤ 21 years of age (Part 1 and Part 2a)
- •> 2 years of age and ≤ 25 years of age (Part 2b)
- •Body surface area ≥ 0.48 m^2 (Part 1 and Part 2b)
- •For patients with CNS tumors or CNS metastasis, there must be no evidence of new CNS hemorrhage of more than punctate size and/or > 3 foci of punctate hemorrhage on baseline MRI for primary CNS tumors ≥ 14 days prior to study entry
- •Karnofsky performance status (PS) 50-100% (> 16 years of age)
- •Lansky PS 50-100% (≤ 16 years of age)
- •Platelet count ≥ 100,000/mm^3 (transfusion independent)
- •ANC ≥ 1,000/mm^3
- •Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions)
- •Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age/gender as follows:
- •0.6 mg/dL (1 to < 2 years of age)
- •0.8 mg/dL (2 to < 6 years of age)
- •1 mg/dL (6 to < 10 years of age)
- •1.2 mg/dL (10 to < 13 years of age)
- •1.5 mg/dL (male ) or 1.4 mg/dL (female) (13 to < 16 years of age)
- •1.7 mg/dL (male) or 1.4 mg/dL (female) ( ≥ 16 years of age)
- •Urine protein:creatinine ratio < 1 OR urinalysis negative for protein OR 24-hour urine protein level < 1 g
- •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •ALT ≤ 110 U/L
- •PT and PTT ≤ 1.2 times ULN
- •INR ≤ 1.2
- •Serum albumin ≥ 2 g/dL
- •No grade > 1 abnormalities of potassium, calcium, magnesium, or phosphorous
- •Supplementation allowed
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Oral contraceptives are not considered effective
- •Adequate cardiac function defined as any of the following:
- •Shortening fraction of ≥ 27% by echocardiogram
- •Ejection fraction of ≥ 50% by gated radionuclide study
- •QTc < 450 msec
- •No history of myocardial infarction, severe or unstable angina, or peripheral vascular disease or familial QTc prolongation
- •Adequate blood pressure defined as ≤ 95th percentile for age, height, and gender
- •Known history of well-controlled seizures allowed
- •Able to swallow whole tablets (Part 1 and Part 2b)
- •No uncontrolled infection
- •No evidence of active bleeding, intratumoral hemorrhage, or bleeding diathesis
- •None of the following conditions within the past 6 months:
- 另有 37 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (pazopanib hydrochloride)
Patients receive oral pazopanib hydrochloride once daily on days 1-28. Courses repeat every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
干预措施: pazopanib hydrochloride (Drug)
Treatment (pazopanib hydrochloride)
Patients receive oral pazopanib hydrochloride once daily on days 1-28. Courses repeat every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
结局指标
主要结局
Maximum-tolerated dose of pazopanib hydrochloride defined as the maximum dose at which fewer that one-third of patients experience DLT
时间窗: 28 days
Graded using the NCI CTCAE version 4.0.
Adverse events according to NCI CTCAE version 4.0
时间窗: Up to 30 days after completion of study treatment
Pharmacokinetics of pazopanib hydrochloride
时间窗: Baseline, days 15, 22, and 27 of course 1 and day 1 of odd courses
Summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).
次要结局
- Overall response to pazopanib hydrochloride according to RECIST criteria(Up to 30 days after completion of study treatment)