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Study of Nifurtimox to Treat Refractory or Relapsed Neuroblastoma or Medulloblastoma

Primary Purpose

Neuroblastoma, Medulloblastoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Nifurtimox
Cyclophosphamide
Topotecan
Sponsored by
Giselle Sholler
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuroblastoma

Eligibility Criteria

undefined - 21 Years (Child, Adult)All SexesDoes not accept 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

Sites / Locations

  • Rady Children's Hospital
  • Connecticut Children's Hospital
  • Arnold Palmer Hospital for Children- MD Anderson
  • Kapiolani Medical Center for Women and Children
  • Tufts Medical Center
  • Helen DeVos Children's Hospital
  • Children's Hospital and Clinics on Minnesota
  • Children's Mercy Hospitals and Clinics
  • Cardinal Glennon Children's Medical Center
  • Levine Children's Hospital
  • Penn State Milton S. Hershey Medical Center and Children's Hospital
  • Medical University of South Carolina
  • Children's Medical Center
  • Texas Children's Cancer and Hematology Centers
  • Primary Children's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Nifurtimox

Arm Description

Outcomes

Primary Outcome Measures

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
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.

Secondary Outcome Measures

Full Information

First Posted
January 14, 2008
Last Updated
September 26, 2023
Sponsor
Giselle Sholler
Collaborators
Bayer
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1. Study Identification

Unique Protocol Identification Number
NCT00601003
Brief Title
Study of Nifurtimox to Treat Refractory or Relapsed Neuroblastoma or Medulloblastoma
Official Title
A Phase II Trial of Nifurtimox for Refractory or Relapsed Neuroblastoma or Medulloblastoma.
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
January 14, 2008 (Actual)
Primary Completion Date
April 28, 2020 (Actual)
Study Completion Date
October 28, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Giselle Sholler
Collaborators
Bayer

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroblastoma, Medulloblastoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
112 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Nifurtimox
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Nifurtimox
Other Intervention Name(s)
Lampit
Intervention Description
30mg/kg/day PO divided into TID dosing q day
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
250 mg/m2/dose in normal saline, IV, infused over 30 minutes on days 1-5 of each cycle.
Intervention Type
Drug
Intervention Name(s)
Topotecan
Other Intervention Name(s)
Hycamptin
Intervention Description
0.75mg/m2/dose, in normal saline, IV, infused over 30 minutes on days 1-5 of each cycle.
Primary Outcome Measure Information:
Title
Number of Participants With Related Adverse Events as a Measure of Safety and Tolerability
Description
Test the safety of nifurtimox in children with relapsed or refractory neuroblastoma or medulloblastoma in combination with cyclophosphamide/topotecan
Time Frame
2 years
Title
Best Radiological Response in Participants Using the RECIST Criteria
Description
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.
Time Frame
2 years

10. Eligibility

Sex
All
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Giselle Sholler, MD
Organizational Affiliation
Beat Childhood Cancer at Atrium Health
Official's Role
Study Chair
Facility Information:
Facility Name
Rady Children's Hospital
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Connecticut Children's Hospital
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06106
Country
United States
Facility Name
Arnold Palmer Hospital for Children- MD Anderson
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Kapiolani Medical Center for Women and Children
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96813
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Helen DeVos Children's Hospital
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503
Country
United States
Facility Name
Children's Hospital and Clinics on Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
Children's Mercy Hospitals and Clinics
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Cardinal Glennon Children's Medical Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
Facility Name
Levine Children's Hospital
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Penn State Milton S. Hershey Medical Center and Children's Hospital
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Children's Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
Texas Children's Cancer and Hematology Centers
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Primary Children's Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.beatcc.org
Description
Beat Childhood Cancer Consortium website

Learn more about this trial

Study of Nifurtimox to Treat Refractory or Relapsed Neuroblastoma or Medulloblastoma

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