A Phase II Study of Fenretinide (NSC# 374551, IND# 40294) in Children With Recurrent/Resistant High Risk Neuroblastoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Response rate
研究概览
简要总结
This phase II trial is studying how well fenretinide works in treating children with recurrent or resistant neuroblastoma. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.
详细描述
OBJECTIVES:
Determine the response rate in pediatric patients with recurrent or resistant high-risk neuroblastoma treated with fenretinide.
Determine the toxic effects of this drug in these patients. Determine the proportion of patients with disease detected only by bone marrow immunocytology, who clear all evidence of disease during treatment with this drug.
Determine minimal residual disease response by marrow and meta-iodobenzylguanidine (MIBG) I 123 scan in patients treated with this drug.
OUTLINE: Patients are stratified according to presence of measurable disease on CT scan/MRI (yes vs no). A third stratum of patients with tumor cells in bone marrow by immunocytology only is enrolled but is not evaluated for response.
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
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of recurrent or resistant/refractory high-risk neuroblastoma by one or both of the following:
- •Histological confirmation
- •Demonstration of tumor cells in bone marrow with increased urinary catecholamines
- •Stratum I:
- •At least 1 unidimensionally measurable lesion*
- •At least 20 mm by MRI and/or CT scan OR at least 10 mm by spiral CT scan
- •Stratum II: Meets one or both of the following criteria:
- •At least 1 site with positive uptake on meta-iodobenzylguanidine (MIBG) I 123 scan
- •Tumor in bilateral bone marrow aspirate/biopsy by routine morphology (no NSE staining only)
- •Stratum III:
- •At least 5 tumor cells/10^6 mononuclear cells in the bone marrow by immunocytology only (on 2 successive bone marrows performed from 1 day to 4 weeks apart)
- •Patients in first response (i.e., patients with persistent tumor at end of frontline therapy, but who have never had disease relapse or progression) must have histological* or morphological (by bone marrow) confirmation** of viable tumor on CT scan, MRI, or MIBG scan after completion of myeloablative therapy (for strata I and II)
- •No catecholamine elevation only
- •Performance status - 0-2
- •At least 2 months
- •Hemoglobin greater than 7.5 g/dL (transfusion allowed)
- •Bilirubin no greater than 1.5 times normal
- •SGPT and SGOT less than 2.5 times normal
- •Creatinine normal for age
- •No hematuria or proteinuria greater than 1+ on urinalysis
- •Calcium less than 11.6 mg/dL
- •Triglycerides less than 300 mg/dL
- •Not pregnant
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No seizure disorders unless on anticonvulsants and well controlled
- •No skin toxicity greater than grade 1
- •Must be able to consume entire intact study capsule in the dosage prescribed for body surface area
- •Recovered from prior immunotherapy
- •At least 7 days since prior anticancer biologic therapy
- •At least 2 days since prior growth factors
- •Prior autologous stem cell transplantation allowed
- •No prior allogeneic stem cell transplantation
- •No concurrent immunomodulating agents
- •At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered
- •No concurrent anticancer chemotherapy
- •No concurrent steroids
- •Recovered from prior radiotherapy
- •At least 4 weeks since prior radiotherapy to target lesion
- •Prior radiotherapy to non target lesions allowed
- •No concurrent radiotherapy to sole measurable lesion for symptom relief
- •Concurrent palliative radiotherapy to non target or localized painful lesions allowed
- •Prior tretinoin or isotretinoin allowed
- •At least 2 weeks since other prior retinoids
- •No prior fenretinide
- •No concurrent supplemental oral or IV vitamin A, ascorbic acid, or vitamin E (except if contained in routine total parenteral nutrition [TPN] vitamin supplements)
- •No concurrent drugs suspected of causing pseudotumor cerebri (e.g., tetracycline, nalidixic acid, nitrofurantoin, phenytoin, sulfonamides, lithium, amiodarone, or vitamin A [except as part of routine TPN supplements])
- •No other concurrent anticancer agents
排除标准
- 未提供
研究组 & 干预措施
Treatment (fenretinide)
Patients receive oral fenretinide 3 times daily (or 2 times daily if over 18 years of age) on days 1-7. Treatment repeats every 3 weeks for up to 30 courses in the absence of disease progression or unacceptable toxicity.
干预措施: fenretinide (Drug)
Treatment (fenretinide)
Patients receive oral fenretinide 3 times daily (or 2 times daily if over 18 years of age) on days 1-7. Treatment repeats every 3 weeks for up to 30 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
Response rate
时间窗: Up to 8 courses of therapy
A responder is defined to be a patient who achieves a best overall response of complete response (CR), very good partial response (VGPR) or partial response (PR).
Toxicity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
时间窗: Up to 5 years
Assessed via a descriptive tabulation of the toxicity rates, overall and by stratum.
次要结局
- Levels of fenretinide(At baseline and during courses 1, 2, and 5)
- Plasma retinol levels(At baseline and during courses 1, 2, and 5)
- Minimal residual disease (MRD) (Stratum 3)(Up to 5 years)