A Phase II Trial of Nifurtimox for Refractory or Relapsed Neuroblastoma or Medulloblastoma.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 112
- 试验地点
- 15
- 主要终点
- Best Radiological Response in Participants Using the RECIST Criteria
研究概览
简要总结
The purpose of this study is to determine whether nifurtimox in combination with cyclophosphamide and topotecan are effective in the treatment of relapsed or refractory neuroblastoma and medulloblastoma.
详细描述
This study is being done to test the effect of a drug, nifurtimox, against neuroblastoma and medulloblastoma in children. Nifurtimox is a drug that has been used in South America for many years to treat a parasitic disease known as Chagas Disease. It is not approved by the Food and Drug Administration for routine use in neuroblastoma or medulloblastoma in the United States, but limited early observations suggest that nifurtimox may have anti tumor activity for neuroblastoma and medulloblastoma.
From the preliminary trials of nifurtimox we have determined a safely tolerated dose of nifurtimox to use in neuroblastoma patients (30mg/kg/day). The dose determined in the Phase I study to be safe, will be the dose used for this study. From clinical experience in South America, we know that children can tolerate nifurtimox when given by mouth, and it appears to have no long-term side effects when used to treat Chagas Disease. Based on our laboratory and animal studies, we believe that drug levels similar to those used to treat Chagas Disease may shrink/kill neuroblastoma cells, especially when combined with other chemotherapy drugs. We do not know whether nifurtimox will shrink/kill tumor cells effectively in children. Therefore, the major goal of the study is to learn if nifurtimox in combination with other chemotherapy drugs is effective in shrinking/killing neuroblastoma and medulloblastoma cells.
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
- •Age: 0-21 years at the time of diagnosis.
- •Diagnosis: Histologic verification at either the time of original diagnosis or relapse of neuroblastoma or medulloblastoma.
- •Disease Status: Refractory or first or multiple relapsed neuroblastoma, or medulloblastoma that has relapsed after, or is refractory to, a chemotherapy-containing treatment regimen.
- •Measurable disease, including at least one of the following:
- •Measurable tumor by CT or MRI
- •For neuroblastoma patients only, a positive MIBG (MIBG not required if subject's neuroblastoma is previously determined to not uptake MIBG), abnormal urinary catecholamine levels, or positive bone marrow biopsy/aspirate.
- •For medulloblastoma patients only, positive CSF cytology
- •Current disease state must be one for which there is currently no known curative therapy.
- •A negative urine pregnancy test is required for female participants of child bearing potential (≥13 years of age).
- •Organ Function Requirements Patients without bone marrow metastases must have an ANC > 500/μl and platelet count >50,000/μl.
- •Patients must have adequate liver function as defined by AST or ALT <10x normal
- •Informed Consent: All patients and/or legal guardians must sign informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines
排除标准
- •Life expectancy <2 months or Lansky score <50%
- •Investigational Drugs: Patients who are currently receiving another investigational drug are excluded from participation.
- •Anti-cancer Agents: Patients who are currently receiving other anticancer agents are not eligible. Patients must have fully recovered from the effects of prior chemotherapy, generally at least 3 weeks from the most recent administration (6 weeks for nitrosoureas).
- •Infection: Patients who have an uncontrolled infection are not eligible until the infection is judged to be well controlled.
- •Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.
- •Compensation for travel related expenses may be available
研究组 & 干预措施
Nifurtimox
干预措施: Nifurtimox (Drug)
Nifurtimox
干预措施: Cyclophosphamide (Drug)
Nifurtimox
干预措施: Topotecan (Drug)
结局指标
主要结局
Best Radiological Response in Participants Using the RECIST Criteria
时间窗: 2 years
Test the efficacy of nifurtimox in children with relapsed or refractory neuroblastoma or medulloblastoma in combination with cyclophosphamide/topotecan Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions, Overall Best Response assessed by CT or MRI, MIBG, and Bone Marrow: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions, bone marrow with CR, and MIBG with CR/PR. Overall Response (OR) = CR + PR.
Number of Participants With Related Adverse Events as a Measure of Safety and Tolerability
时间窗: 2 years
Test the safety of nifurtimox in children with relapsed or refractory neuroblastoma or medulloblastoma in combination with cyclophosphamide/topotecan
次要结局
未报告次要终点
研究者
Giselle Sholler
Study Chair
Milton S. Hershey Medical Center