Study of Nifurtimox to Treat Refractory or Relapsed Neuroblastoma or Medulloblastoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Spectrum Health Hospitals
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Giselle Sholler, Spectrum Health Hospitals
ClinicalTrials.gov Identifier:
NCT00601003
First received: January 14, 2008
Last updated: February 5, 2014
Last verified: February 2014
  Purpose

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 Intervention Phase
Neuroblastoma
Medulloblastoma
Drug: Nifurtimox
Drug: Cyclophosphamide
Drug: Topotecan
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Nifurtimox for Refractory or Relapsed Neuroblastoma or Medulloblastoma.

Resource links provided by NLM:


Further study details as provided by Spectrum Health Hospitals:

Primary Outcome Measures:
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Quality of life and neurocognitive evaluation/questionnaire. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: February 2008
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00601003

Contacts
Contact: Genevieve Bergendahl, RN 616-267-0335 genevieve.bergendahl@helendevoschildrens.org
Contact: Alyssa VanderWerff (616) 267-0327 alyssa.vanderwerff@helendevoschildrens.org

Locations
United States, California
Rady Children's Hospital Recruiting
San Diego, California, United States, 92123
Contact: Mehrzad Milburn    858-966-8155      
Principal Investigator: William Roberts, MD         
United States, Connecticut
Connecticut Children's Hospital Recruiting
Hartford, Connecticut, United States, 06106
Contact: Jennifer Hylton    860-545-9337    Jhylton02@connecticutchildrens.org   
Principal Investigator: Nehal Parikh, MD         
United States, Florida
Arnold Palmer Hospital for Children- MD Anderson Recruiting
Orlando, Florida, United States, 32806
Contact: Michelle Pope, RN    321-841-8588      
Principal Investigator: Don Eslin, MD         
United States, Hawaii
Kapiolani Medical Center for Women and Children Recruiting
Honolulu, Hawaii, United States, 96813
Contact: Andrea Siu, MPH    808-535-7169    andrea.siu@kapiolani.org   
Principal Investigator: Randal Wada, MD         
United States, Michigan
Helen DeVos Children's Hospital Recruiting
Grand Rapids, Michigan, United States, 49503
Contact: Shannon MacKeigan    616-267-1162    shannon.mackeigan@helendevoschildrens.org   
Principal Investigator: Deanna Mitchell, MD         
Principal Investigator: Giselle Sholler, MD         
United States, Missouri
Children's Mercy Hospitals and Clinics Recruiting
Kansas City, Missouri, United States, 64108
Contact: Sara Soliman, RN    816-855-1977    sjsoliman@cmh.edu   
Principal Investigator: Kathleen Neville, MD         
Cardinal Glennon Children's Medical Center Recruiting
St. Louis, Missouri, United States, 63104
Contact: Katherine Maxwell, RN    314-268-4000      
Principal Investigator: William Ferguson, MD         
United States, North Carolina
Levine Children's Hospital Recruiting
Charlotte, North Carolina, United States, 28204
Contact: Nicole Turner, RN    980-442-2355    felisha.turner@carolinashealthcare.org   
Principal Investigator: Javier Oesterheld, MD         
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Jacqueline Kraveka, MD    843-792-2957      
Principal Investigator: Jaqueline Kraveka, MD         
United States, Texas
Texas Children's Cancer and Hematology Centers Recruiting
Houston, Texas, United States, 77030
Contact: Bridget Medina, BS, CCRC, CCRP    832-824-6858    bnmedina@txch.org   
Principal Investigator: Peter Zage, MD, PhD         
Sponsors and Collaborators
Giselle Sholler
Bayer
Investigators
Study Chair: Giselle Sholler, MD The Spectrum Health Group
  More Information

Additional Information:
No publications provided

Responsible Party: Giselle Sholler, Study Chair, Spectrum Health Hospitals
ClinicalTrials.gov Identifier: NCT00601003     History of Changes
Other Study ID Numbers: V0706
Study First Received: January 14, 2008
Last Updated: February 5, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Medulloblastoma
Neuroblastoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral
Cyclophosphamide
Nifurtimox
Alkylating Agents
Anti-Infective Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antiparasitic Agents
Antiprotozoal Agents
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Trypanocidal Agents

ClinicalTrials.gov processed this record on October 23, 2014