Safety Study of Nifurtimox for Relapsed or Refractory Neuroblastoma

Sponsor

University of Vermont (Other)

Overall Status

Completed

CT.gov ID

NCT00486564

Collaborator

St. Louis University (Other)

Enrollment

Locations

Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

There is currently no curative treatment for children with relapsed/refractory neuroblastoma, and for these children the 5 year survival rate is <10%. As such, new therapeutic approaches are needed to treat these children. This Phase 1 clinical trial is specifically designed to test the safety and toxicity of nifurtimox when given in combination with cyclophosphamide and topotecan for the treatment of relapsed and/or refractory neuroblastoma . Prior to study opening, 3 pediatric patients with neuroblastoma have received nifurtimox in combination with this chemotherapy regimen, and all have had significant measurable responses without undue toxicity. These case reports, as well as our in vitro and in vivo investigations into the biologic effect of nifurtimox on neuroblastoma cells has prompted the development of this Phase I study. This Phase I study will involve a dose escalation trial of daily oral nifurtimox alone for one 21 day cycle of therapy, followed by continuation of nifurtimox with the addition of standard doses of cyclophosphamide (5 days) and topotecan (5 days) for 3 additional 21 day cycles. Our primary aim is to evaluate the safety of nifurtimox alone and in combination with these chemotherapy agents in multiply relapsed/refractory patients. Our secondary aim will be to evaluate the pharmacokinetics of nifurtimox as well as treatment response.

Condition or Disease	Intervention/Treatment	Phase
Neuroblastoma	Drug: Nifurtimox	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Trial of Nifurtimox for Relapsed or Refractory Neuroblastoma

Study Start Date :

Nov 1, 2006

Actual Primary Completion Date :

Nov 1, 2007

Actual Study Completion Date :

Jun 1, 2009

Outcome Measures

Primary Outcome Measures

Test the safety of nifurtimox in children with relapsed or refractory neuroblastoma alone and in combination with cyclophosphamide and topotecan. [3 months]

Secondary Outcome Measures

To evaluate the pharmacokinetic profile of nifurtimox alone and in combination with cyclophosphamide and topotecan. [3 months]
To determine the response rate to treatment with nifurtimox combined with cyclophosphamide/topotecan [3 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age: 0-21 years at the time of study entry.
Diagnosis: Histologic verification of neuroblastoma at original diagnosis or relapse.
Disease Status: Refractory or first or multiple relapsed neuroblastoma with measurable disease by radiographic scan (CT or MRI and MIBG), abnormal urinary catecholamine levels, or positive bone marrow biopsy/aspirate. MIBG not required if subject's neuroblastoma is previously determined to not uptake MIBG isotope (not MIBG avid).
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).
Patients must have adequate liver function as defined by AST or ALT <10x normal and a bilirubin <1.5mg/dl
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 <3 months
Investigational Drugs: Patients who are currently receiving another investigational drug.
Anti-cancer Agents: Patients who are currently receiving other anticancer agents.
Infection: Patients who have an uncontrolled infection.
Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study.
Patients may not receive bisphosphonates (i.e. Zometa) within 7 days of start of therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Louis University/Cardinal Glennon Childrens Medical Center	St. Louis	Missouri	United States	63104
2	University of Vermont/Vermont Children's Hospital	Burlington	Vermont	United States	05401