Study of Nifurtimox to Treat Refractory or Relapsed Neuroblastoma or Medulloblastoma

Neuroblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00601003
• Other study ID #: V0706
• Status: Completed
• Phase: Phase 2
• Start date: January 14, 2008
• Est. completion date: October 28, 2022

Study information

• Verified date: April 2024
• Source: Milton S. Hershey Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 112
• Est. completion date: October 28, 2022
• Est. primary completion date: April 28, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• Medulloblastoma
• Neuroblastoma

Intervention

Drug:
• Nifurtimox
30mg/kg/day PO divided into TID dosing q day
• Cyclophosphamide
250 mg/m2/dose in normal saline, IV, infused over 30 minutes on days 1-5 of each cycle.
• Topotecan
0.75mg/m2/dose, in normal saline, IV, infused over 30 minutes on days 1-5 of each cycle.

Locations

Country	Name	City	State
United States	Tufts Medical Center	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Levine Children's Hospital	Charlotte	North Carolina
United States	Children's Medical Center	Dallas	Texas
United States	Helen DeVos Children's Hospital	Grand Rapids	Michigan
United States	Connecticut Children's Hospital	Hartford	Connecticut
United States	Penn State Milton S. Hershey Medical Center and Children's Hospital	Hershey	Pennsylvania
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Texas Children's Cancer and Hematology Centers	Houston	Texas
United States	Children's Mercy Hospitals and Clinics	Kansas City	Missouri
United States	Children's Hospital and Clinics on Minnesota	Minneapolis	Minnesota
United States	Arnold Palmer Hospital for Children- MD Anderson	Orlando	Florida
United States	Cardinal Glennon Children's Medical Center	Saint Louis	Missouri
United States	Primary Children's Hospital	Salt Lake City	Utah
United States	Rady Children's Hospital	San Diego	California

Sponsors (2)

Lead Sponsor	Collaborator
Giselle Sholler	Bayer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Related Adverse Events as a Measure of Safety and Tolerability	Test the safety of nifurtimox in children with relapsed or refractory neuroblastoma or medulloblastoma in combination with cyclophosphamide/topotecan	2 years
Primary	Best Radiological Response in Participants Using the RECIST Criteria	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.	2 years

External Links

•   Beat Childhood Cancer Consortium website