Study of Nifurtimox to Treat Refractory or Relapsed Neuroblastoma or Medulloblastoma

Study ID
STU 052014-083

Study Sites

  • Children’s Medical Center (Dallas, Plano, Southlake)

Caitlyn Ambrose

Principal Investigator
Theodore Laetsch, M.D.

Official Title

A Phase II Trial of Nifurtimox for Refractory or Relapsed Neuroblastoma or Medulloblastoma.

Brief Overview

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.


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.


Inclusion Criteria:
- 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
Exclusion Criteria:
- 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