Study of Nifurtimox to Treat Refractory or Relapsed Neuroblastoma or Medulloblastoma

Sponsor

Wake Forest University Health Sciences (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00601003

Collaborator

Bayer (Industry)

112

Enrollment

Locations

Arm

190

Anticipated Duration (Months)

7.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Neuroblastoma Medulloblastoma	Drug: Nifurtimox Drug: Cyclophosphamide Drug: Topotecan	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

112 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 1, 2008

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nifurtimox	Drug: Nifurtimox 30mg/kg/day PO divided into TID dosing q day Other Names: Lampit Drug: Cyclophosphamide 250 mg/m2/dose in normal saline, IV, infused over 30 minutes on days 1-5 of each cycle. Other Names: Cytoxan Drug: Topotecan 0.75mg/m2/dose, in normal saline, IV, infused over 30 minutes on days 1-5 of each cycle. Other Names: Hycamptin

Arm

Intervention/Treatment

Experimental: Nifurtimox

Drug: Nifurtimox

30mg/kg/day PO divided into TID dosing q day

Other Names:

Lampit

Drug: Cyclophosphamide

250 mg/m2/dose in normal saline, IV, infused over 30 minutes on days 1-5 of each cycle.

Other Names:

Cytoxan

Drug: Topotecan

0.75mg/m2/dose, in normal saline, IV, infused over 30 minutes on days 1-5 of each cycle.

Other Names:

Hycamptin

Outcome Measures

Primary Outcome Measures

Number of Participants with Adverse Events as a Measure of Safety and Tolerability [2 years]
Test the safety of nifurtimox in children with relapsed or refractory neuroblastoma or medulloblastoma in combination with cyclophosphamide/topotecan
Best Radiological Response in Participants using the RECIST criteria [2 years]
Test the efficacy of nifurtimox in children with relapsed or refractory neuroblastoma or medulloblastoma in combination with cyclophosphamide/topotecan

Secondary Outcome Measures

Evaluate the correlation between the pharmacologic serum levels of nifurtimox (in combination with cyclophosphamide and topotecan) with tumor response. [2 years]
Quality of life and neurocognitive evaluation/questionnaire. [2 years]
Biology studies to include: genomic analysis of cells pre- and post- treatment, correlation of in vitro response to in vivo response, flow cytometry of tumor burden in bone marrow and biomarker development. [2 years]

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 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rady Children's Hospital	San Diego	California	United States	92123
2	Connecticut Children's Hospital	Hartford	Connecticut	United States	06106
3	Arnold Palmer Hospital for Children- MD Anderson	Orlando	Florida	United States	32806
4	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96813
5	Tufts Medical Center	Boston	Massachusetts	United States	02111
6	Helen DeVos Children's Hospital	Grand Rapids	Michigan	United States	49503
7	Children's Hospital and Clinics on Minnesota	Minneapolis	Minnesota	United States	55404
8	Children's Mercy Hospitals and Clinics	Kansas City	Missouri	United States	64108
9	Cardinal Glennon Children's Medical Center	Saint Louis	Missouri	United States	63104
10	Levine Children's Hospital	Charlotte	North Carolina	United States	28204
11	Penn State Milton S. Hershey Medical Center and Children's Hospital	Hershey	Pennsylvania	United States	17033
12	Medical University of South Carolina	Charleston	South Carolina	United States	29425
13	Children's Medical Center	Dallas	Texas	United States	75235
14	Texas Children's Cancer and Hematology Centers	Houston	Texas	United States	77030
15	Primary Children's Hospital	Salt Lake City	Utah	United States	84113