NCT00646230已完成1 期
A Phase I Study of Intravenous (Emulsion) Fenretinide in Children With Recurrent or Resistant Neuroblastoma
New Approaches to Neuroblastoma Therapy Consortium22 个研究点 分布在 2 个国家目标入组 17 人开始时间: 2006年12月1日最近更新:
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
- 入组人数
- 17
- 试验地点
- 22
- 主要终点
- To determine the plasma pharmacokinetics of intravenous emulsion 4-HPR given on this schedule.
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as fenretinide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
PURPOSE: This phase I trial is studying the side effects and best dose of intravenous fenretinide in treating young patients with recurrent or resistant neuroblastoma.
详细描述
OBJECTIVES:
Primary
- To determine the maximum tolerated dose of fenretinide when given as a continuous intravenous infusion in young patients with recurrent and/or resistant neuroblastoma.
- To define the toxicities of this drug in these patients.
- To determine the plasma pharmacokinetics of this drug in these patients.
Secondary
- To determine the response rate in patients treated with this drug.
- To determine the bioavailability of fenretinide in normal peripheral blood mononuclear cells as a surrogate marker for drug bioavailability to tumor tissue.
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
- 0 Years 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Diagnosis of neuroblastoma either by histological confirmation and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines
- •Differentiating ganglioneuroblastoma allowed
- •No histological evidence only of ganglioneuroma by tumor biopsy or bone marrow biopsy
- •High-risk disease meeting at least one of the following criteria:
- •Recurrent/progressive disease at any time
- •Refractory disease (i.e., less than a partial response to front-line therapy that included ≥ 4 courses of chemotherapy)
- •Persistent disease after at least a partial response to front-line therapy (i.e., still has residual disease by MIBG, CT/MRI, or bone marrow biopsy)
- •Biopsy of at least one residual site demonstrating viable neuroblastoma required (tumor by bone marrow morphology is considered adequate documentation of disease)
- •Measurable disease meeting at least one of the following criteria:
- •Measurable tumor on MRI or CT scan, defined as at least one unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
- •For patients with persistent disease, a biopsy* of bone marrow or bone or soft tissue site must have demonstrated viable neuroblastoma
- •MIBG scan with positive uptake at a minimum of one site
- •For patients with persistent disease, a biopsy* of a MIBG positive site must have demonstrated viable neuroblastoma
- •Bone marrow with tumor cells seen on routine morphology (not by NSE staining only) of bilateral aspirate and/or biopsy of one bone marrow sample NOTE: *If the lesion was irradiated, the biopsy must have been done at least 4 weeks after completion of radiotherapy
- •No CNS parenchymal or meningeal-based lesions
- •Skull-based tumor lesions with or without intracranial extension are allowed provided there are no neurologic signs or symptoms or hydrocephalus related to the lesion
- •Patients with a history of complete surgical resection of CNS lesions are eligible provided there is no evidence of CNS lesions by MRI or CT scan at study entry
- •Patients with a history of CNS lesions must be off corticosteroid therapy for CNS lesions for ≥ 4 weeks
- •PATIENT CHARACTERISTICS:
- •Performance status 0-2
- •Life expectancy ≥ 2 months
- •ANC ≥ 500/mm³
- •Platelet count ≥ 50,000/mm³ (transfusion independent)
- •Hemoglobin ≥ 8.0 g/dL (transfusion independent)
- •Serum creatinine ≤ 1.5 times normal for age
- •Total bilirubin ≤ 1.5 times normal for age
- •ALT and AST ≤ 3 times normal for age
- •Serum triglycerides < 300 mg/dL
- •Serum calcium < 11.6 mg/dL
- •Lipase normal for age
- •PT/PTT ≤ 1.5 times upper limit of normal for age (without fresh frozen plasma support; vitamin K allowed)
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception prior to, during, and for 2 months after completion of study treatment
- •LVEF ≥ 55% by ECHO or MUGA scan OR fractional shortening ≥ 27% by ECHO
- •No EKG abnormality
- •No dyspnea at rest or requirement for oxygen
- •No hematuria and/or proteinuria > 1+ on urinalysis
- •No known history of allergy to egg products
- •No known history of allergy to soy bean oil
- •No skin toxicity > grade 1 per CTCAE v3
- •Seizure disorder allowed if seizures are controlled on anticonvulsants and the anticonvulsant(s) is not contraindicated
- •Known genetic, metabolic, or psychiatric conditions, or other ongoing serious medical issues must be approved by the study chair prior to study registration
- •PRIOR CONCURRENT THERAPY:
- •Recovered from all prior chemotherapy, immunotherapy, or radiotherapy
- •More than 3 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and/or biologic therapy without stem cell support
- •More than 7 days since prior hematopoietic growth factors
- •No prior radiotherapy to the only site of measurable disease unless there has been subsequent disease progression at that site or a biopsy of that site showed viable neuroblastoma ≥ 4 weeks after completion of radiotherapy
- •Prior CNS irradiation allowed
- 另有 20 项未显示
排除标准
- 未提供
研究组 & 干预措施
Single arm of CIV infusion of emulsion 4-HPR
Experimental
Single arm study of continuous intravenous infusion (CIV) of emulsion 4-HPR
干预措施: pharmacological study (Other)
Single arm of CIV infusion of emulsion 4-HPR
Experimental
Single arm study of continuous intravenous infusion (CIV) of emulsion 4-HPR
干预措施: fenretinide (Drug)
Single arm of CIV infusion of emulsion 4-HPR
Experimental
Single arm study of continuous intravenous infusion (CIV) of emulsion 4-HPR
干预措施: high performance liquid chromatography (Other)
结局指标
主要结局
To determine the plasma pharmacokinetics of intravenous emulsion 4-HPR given on this schedule.
时间窗: Pharmacokinetic Profile of Fenretinide - blood levels to be measured in Cycle #1 D0 Hr0, Hrs 6, 12, 24, 36, 48, 72, 96, 120 and end of infusion, then +2 hrs, +48 hrs post infusion. Cycle #2 D1 Hr0 (pre-infusion), then +48 hrs, at the end of infusion.
To define the toxicities of intravenous emulsion 4-HPR given on this schedule.
时间窗: Adverse events, clinically significant changes in lab results or vitals will be captured throughout the duration of the study.
Adverse events, clinically significant changes in lab results or vitals will be captured throughout the duration of the study.
To determine the maximum tolerated dose of intravenous emulsion 4-HPR given as a continuous intravenous infusion (CIV) for five days (120 hours) every three weeks in children with recurrent and/or resistant neuroblastoma.
时间窗: Tolerability of drug will be assessed throughout the study.
次要结局
- To determine the response rate to intravenous emulsion 4-HPR in patients with recurrent and/or resistant neuroblastoma within the confines of a Phase I study.(Disease response will be assessed at baseline, End of Cycle #2, End of Cycle #6 and every 4 weeks thereafter.)
- To determine the bioavailability to tumor cells of 4-HPR delivered as an intravenous emulsion in normal peripheral blood mononuclear cells (PBMC) as a tumor cell surrogate tissue.(Assessed Cycle #1 D0 Hr0, D2, +48hrs after start of infusion and C#2 one time for patients >20kg.)
- To describe the results of the five gene Five-gene TaqMan® Low Density Array (TLDA) assay for neuroblastoma tumor cells in the bone marrow done at timepoints when bone marrow response is being evaluated by morphology during this therapy.(Assessed at the end of Cycle #2 & Cycle #6 and then every 4 cycles therafter.)
研究者
Nant Operations Center
NANT Operations Center
Children's Hospital Los Angeles
研究点 (22)
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