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Study of Nifurtimox to Treat Refractory or Relapsed Neuroblastoma or Medulloblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00601003
Recruitment Status : Active, not recruiting
First Posted : January 25, 2008
Last Update Posted : September 9, 2019
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Giselle Sholler, Spectrum Health Hospitals

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.

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Study Type : Interventional  (Clinical Trial)
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 : February 2008
Estimated Primary Completion Date : May 1, 2020
Estimated Study Completion Date : December 1, 2020


Arm Intervention/treatment
Experimental: Nifurtimox Drug: Nifurtimox
30mg/kg/day PO divided into TID dosing q day
Other Name: Lampit

Drug: Cyclophosphamide
250 mg/m2/dose in normal saline, IV, infused over 30 minutes on days 1-5 of each cycle.
Other Name: Cytoxan

Drug: Topotecan
0.75mg/m2/dose, in normal saline, IV, infused over 30 minutes on days 1-5 of each cycle.
Other Name: Hycamptin




Primary Outcome Measures :
  1. Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 2 years ]
    Test the safety of nifurtimox in children with relapsed or refractory neuroblastoma or medulloblastoma in combination with cyclophosphamide/topotecan

  2. Best Radiological Response in Participants using the RECIST criteria [ Time Frame: 2 years ]
    Test the efficacy of nifurtimox in children with relapsed or refractory neuroblastoma or medulloblastoma in combination with cyclophosphamide/topotecan


Secondary Outcome Measures :
  1. Evaluate the correlation between the pharmacologic serum levels of nifurtimox (in combination with cyclophosphamide and topotecan) with tumor response. [ Time Frame: 2 years ]
  2. Quality of life and neurocognitive evaluation/questionnaire. [ Time Frame: 2 years ]
  3. 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. [ Time Frame: 2 years ]


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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00601003


Locations
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United States, California
Rady Children's Hospital
San Diego, California, United States, 92123
United States, Connecticut
Connecticut Children's Hospital
Hartford, Connecticut, United States, 06106
United States, Florida
Arnold Palmer Hospital for Children- MD Anderson
Orlando, Florida, United States, 32806
United States, Hawaii
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, United States, 96813
United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111
United States, Michigan
Helen DeVos Children's Hospital
Grand Rapids, Michigan, United States, 49503
United States, Minnesota
Children's Hospital and Clinics on Minnesota
Minneapolis, Minnesota, United States, 55404
United States, Missouri
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, United States, 64108
Cardinal Glennon Children's Medical Center
Saint Louis, Missouri, United States, 63104
United States, North Carolina
Levine Children's Hospital
Charlotte, North Carolina, United States, 28204
United States, Pennsylvania
Penn State Milton S. Hershey Medical Center and Children's Hospital
Hershey, Pennsylvania, United States, 17033
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Texas
Children's Medical Center
Dallas, Texas, United States, 75235
Texas Children's Cancer and Hematology Centers
Houston, Texas, United States, 77030
United States, Utah
Primary Children's Hospital
Salt Lake City, Utah, United States, 84113
Sponsors and Collaborators
Giselle Sholler
Bayer
Investigators
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Study Chair: Giselle Sholler, MD The Spectrum Health Group
Additional Information:
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Responsible Party: Giselle Sholler, Study Chair, Spectrum Health Hospitals
ClinicalTrials.gov Identifier: NCT00601003    
Other Study ID Numbers: V0706
First Posted: January 25, 2008    Key Record Dates
Last Update Posted: September 9, 2019
Last Verified: September 2019
Additional relevant MeSH terms:
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Neuroblastoma
Medulloblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Glioma
Nifurtimox
Cyclophosphamide
Topotecan
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Trypanocidal Agents
Antiprotozoal Agents
Antiparasitic Agents