Study of Nifurtimox to Treat Refractory or Relapsed Neuroblastoma or Medulloblastoma - Full Text View

Sponsors and Collaborators:	University of Vermont Bayer Baylor University St. Louis University Brown University Rutgers University Fletcher Allen Health Care
Information provided by:	University of Vermont
ClinicalTrials.gov Identifier:	NCT00601003

Purpose

The purpose of this study is to determine whether nifurtimox alone and 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 Drug: Zolendronic acid	Phase II

MedlinePlus related topics: Cancer Neuroblastoma

Drug Information available for: Cyclophosphamide Topotecan hydrochloride Topotecan Zoledronic acid Nifurtimox

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Phase II Trial of Nifurtimox for Refractory or Relapsed Neuroblastoma or Medulloblastoma.

Further study details as provided by University of Vermont:

Primary Outcome Measures:

Test the efficacy and safety of nifurtimox in children with relapsed or refractory neuroblastoma or medulloblastoma, both alone and in combination with cyclophosphamide/topotecan, plus—in patients with bone metastases—zoledronic acid. [ Time Frame: Ongoing ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Evaluate the correlation between the pharmacologic serum levels of nifurtimox (given alone and in combination with cyclophosphamide and topotecan) with tumor response. [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
Quality of life and neurocognitive evaluation/questionnaire. [ Time Frame: Ongoing ] [ 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: Ongoing ] [ Designated as safety issue: No ]

Estimated Enrollment:	100
Study Start Date:	January 2008
Estimated Study Completion Date:	July 2010
Estimated Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Intervention Details:

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

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

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

4 mg/m2 IV (max = 4 mg) over 30 minutes on Day 1 only of each cycle for neuroblastoma patients with bone metastases only.

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 alone and 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.

Contacts and Locations

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

Contacts

Contact: Genevieve Johnson, RN	802-847-2850	genevieve.johnson@uvm.edu
Contact: Giselle Sholler, MD	802-847-2850	giselle.sholler@uvm.edu

Locations

United States, Vermont
UVM/FAHC	Recruiting
Burlington, Vermont, United States, 05401
Principal Investigator: Giselle Sholler, MD
Sub-Investigator: Alan Homans, MD

Sponsors and Collaborators

University of Vermont

Bayer

Baylor University

St. Louis University

Brown University

Rutgers University

Fletcher Allen Health Care

Investigators

Study Chair:

Giselle Sholler, MD

University of Vermont

More Information

Responsible Party:	University of Vermont ( Giselle Sholler, MD )
Study ID Numbers:	V0706, CHRMS# 08-106, PRC # V0706
Study First Received:	January 14, 2008
Last Updated:	January 24, 2008
ClinicalTrials.gov Identifier:	NCT00601003
Health Authority:	United States: Food and Drug Administration

Study placed in the following topic categories:

Neuroectodermal Tumors, Primitive
Zoledronic acid
Cyclophosphamide
Neuroblastoma
Nifurtimox
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal

Medulloblastoma
Neuroepithelioma
Glioma
Topotecan
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Anti-Infective Agents
Trypanocidal Agents
Antiprotozoal Agents
Neoplasms by Histologic Type
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Immunosuppressive Agents

Pharmacologic Actions
Antiparasitic Agents
Neoplasms
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Neoplasms, Neuroepithelial
Antirheumatic Agents
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009