A Phase I Study of Sunitinib (SU11248), an Oral Multi-Targeted Tyrosine Kinase Inhibitor, in Children With Refractory Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 17
- 主要终点
- Adverse events as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
研究概览
简要总结
This phase I trial is studying the side effects and best dose of sunitinib in treating young patients with refractory solid tumors. Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth and by blocking blood flow to the tumor.
详细描述
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose (MTD) and recommended phase II dose of sunitinib malate in pediatric patients with refractory solid tumors.
II. Determine the toxicity of this regimen in these patients. III. Characterize the pharmacokinetics of this regimen in these patients. IV. Evaluate the tolerability and pharmacokinetic profile of sunitinib malate capsule contents sprinkled over applesauce or yogurt using the recommended phase II dose.
SECONDARY OBJECTIVES:
I. Determine, preliminarily, the antitumor effects of this regimen in these patients.
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 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed solid tumor (not required for patients with intrinsic brain stem tumors or optic pathway gliomas)
- •Recurrent or refractory disease
- •Measurable or evaluable disease
- •No known curative therapy or therapy proven to prolong survival with an acceptable quality of life exists
- •Patients with metastatic bone marrow disease are eligible but are not evaluable for hematologic toxicity
- •Must not be refractory to red blood cell or platelet transfusions
- •Primary CNS tumors or known CNS metastases allowed
- •Neurological deficits must have been relatively stable for ≥ 1 week before study enrollment
- •No imaging evidence of prior intracranial hemorrhage
- •No evidence of new CNS hemorrhage on baseline MRI obtained within 14 days before study enrollment (ECHO gradient MRI sequences per institutional guidelines required for evaluation of CNS hemorrhage)
- •The presence of small punctuate CNS hemorrhage on these scans will exclude a patient from participation
- •No known bone marrow metastatic disease
- •No tumors involving the pleural surface
- •Karnofsky performance status (PS) 50-100% (> 10 years of age) OR Lansky PS 50-100% (≤ 10 years of age)
- •Absolute neutrophil count ≥ 1,000/mm³*
- •Platelet count ≥ 100,000/mm³ (transfusion independent)*
- •Hemoglobin ≥ 8.0 g/dL (transfusions allowed)*
- •Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR creatinine based on age/gender as follows:
- •No greater than 0.8 mg/dL (2 to 5 years of age)
- •No greater than 1 mg/dL (6 to 9 years of age)
- •No greater than 1.2 mg/dL (10 to 12 years of age)
- •No greater than 1.5 mg/dL (male) OR 1.4 mg/dL (female) (13 to 15 years of age)
- •No greater than 1.7 mg/dL (male) OR 1.4 mg/dL (female) (≥ 16 years of age)
- •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •ALT and AST ≤ 2.5 times ULN (≤ 5 times ULN for liver metastases)
- •Albumin ≥ 2 g/dL
- •LVEF or shortening fraction normal
- •Corrected QT interval ≤ 450 msec
- •Amylase ≤ 1.5 times ULN
- •Lipase ≤ 1.5 times ULN
- •Body surface area ≥ 0.5 m² (≥ 0.4 m² for part B)
- •Blood pressure within ULN
- •Not pregnant or nursing
- •Fertile patients must use effective contraception
- •No uncontrolled infection
- •Able to swallow sunitinib malate capsules (part A only)
- •No pre-existing thyroid abnormality (hyper- or hypothyroidism) with unstable thyroid function
- •No prior CNS hemorrhage
- •No history of allergic reaction attributed to sunitinib malate or component of sunitinib malate capsules
- •No allergy to both applesauce and yogurt (part B only)
- •Recovered from prior therapy
- •No prior sunitinib malate
- •No prior anthracycline (any dose)
- •No prior radiotherapy to a radiation field that included the heart(including total body or craniospinal irradiation)
- •At least 3 months since prior stem cell transplantation or rescue (without total-body irradiation) and no evidence of graft-vs-host disease
- •At least 2 weeks since prior local, palliative, small-port radiotherapy (at least 6 months for radiation to ≥ 50% of pelvis)
- •At least 6 weeks since other prior substantial bone marrow radiotherapy
- •At least 3 weeks since prior myelosuppressive therapy (6 weeks for nitrosoureas)
- •At least 1 week since prior antineoplastic biologic agents
- •At least 1 week since prior and no concurrent hematopoietic growth factors
- 另有 26 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (enzyme inhibitor therapy)
PART A: Patients receive oral sunitinib malate once daily on days 1-28 days. Treatment repeats every 42 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.
PART B: Patients receive sunitinib malate capsule contents sprinkled over applesauce or yogurt once daily on days 1-28. Treatment repeats every 42 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. After the first course, patients may switch to capsule formulation for convenience.
干预措施: sunitinib malate (Drug)
Treatment (enzyme inhibitor therapy)
PART A: Patients receive oral sunitinib malate once daily on days 1-28 days. Treatment repeats every 42 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.
PART B: Patients receive sunitinib malate capsule contents sprinkled over applesauce or yogurt once daily on days 1-28. Treatment repeats every 42 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. After the first course, patients may switch to capsule formulation for convenience.
干预措施: pharmacological study (Other)
Treatment (enzyme inhibitor therapy)
PART A: Patients receive oral sunitinib malate once daily on days 1-28 days. Treatment repeats every 42 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.
PART B: Patients receive sunitinib malate capsule contents sprinkled over applesauce or yogurt once daily on days 1-28. Treatment repeats every 42 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. After the first course, patients may switch to capsule formulation for convenience.
干预措施: dynamic contrast-enhanced magnetic resonance imaging (Procedure)
Treatment (enzyme inhibitor therapy)
PART A: Patients receive oral sunitinib malate once daily on days 1-28 days. Treatment repeats every 42 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.
PART B: Patients receive sunitinib malate capsule contents sprinkled over applesauce or yogurt once daily on days 1-28. Treatment repeats every 42 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. After the first course, patients may switch to capsule formulation for convenience.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Adverse events as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
时间窗: Weekly during course 1, assessed up to 35 days
Pharmacokinetics of sunitinib malate using liquid spectrometry/mass spectroscopy methods
时间窗: At baseline and days 1, 7, 14, 21, and 28 of course 1
Tolerability and pharmacokinetic profile of capsule contents sprinkled over applesauce or yogurt
时间窗: At baseline and days 1, 7, 14, 21, and 28 of course 1
MTD and recommended phase II dose
时间窗: During course 1 of therapy
MTD will be the maximum dose at which fewer than one-third of patients experience dose-limiting toxicity (DLT).
次要结局
- Correlative studies(Days 1 and 28 of course 1)