Safety Study of Nifurtimox for Relapsed or Refractory Neuroblastoma

This study has been completed.
Sponsor:
Collaborator:
St. Louis University
Information provided by:
University of Vermont
ClinicalTrials.gov Identifier:
NCT00486564
First received: June 12, 2007
Last updated: October 22, 2009
Last verified: October 2009
  Purpose

There is currently no curative treatment for children with relapsed/refractory neuroblastoma, and for these children the 5 year survival rate is <10%. As such, new therapeutic approaches are needed to treat these children. This Phase 1 clinical trial is specifically designed to test the safety and toxicity of nifurtimox when given in combination with cyclophosphamide and topotecan for the treatment of relapsed and/or refractory neuroblastoma . Prior to study opening, 3 pediatric patients with neuroblastoma have received nifurtimox in combination with this chemotherapy regimen, and all have had significant measurable responses without undue toxicity. These case reports, as well as our in vitro and in vivo investigations into the biologic effect of nifurtimox on neuroblastoma cells has prompted the development of this Phase I study. This Phase I study will involve a dose escalation trial of daily oral nifurtimox alone for one 21 day cycle of therapy, followed by continuation of nifurtimox with the addition of standard doses of cyclophosphamide (5 days) and topotecan (5 days) for 3 additional 21 day cycles. Our primary aim is to evaluate the safety of nifurtimox alone and in combination with these chemotherapy agents in multiply relapsed/refractory patients. Our secondary aim will be to evaluate the pharmacokinetics of nifurtimox as well as treatment response.


Condition Intervention Phase
Neuroblastoma
Drug: Nifurtimox
Phase 1

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

Resource links provided by NLM:


Further study details as provided by University of Vermont:

Primary Outcome Measures:
  • Test the safety of nifurtimox in children with relapsed or refractory neuroblastoma alone and in combination with cyclophosphamide and topotecan. [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To evaluate the pharmacokinetic profile of nifurtimox alone and in combination with cyclophosphamide and topotecan. [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • To determine the response rate to treatment with nifurtimox combined with cyclophosphamide/topotecan [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: November 2006
Study Completion Date: June 2009
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Nifurtimox
    Escalating dose by cohort starting at 20mg/kg/day. PO drug taken TID.
  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age: 0-21 years at the time of study entry.
  2. Diagnosis: Histologic verification of neuroblastoma at original diagnosis or relapse.
  3. Disease Status: Refractory or first or multiple relapsed neuroblastoma with measurable disease by radiographic scan (CT or MRI and MIBG), abnormal urinary catecholamine levels, or positive bone marrow biopsy/aspirate. MIBG not required if subject's neuroblastoma is previously determined to not uptake MIBG isotope (not MIBG avid).
  4. Current disease state must be one for which there is currently no known curative therapy.
  5. A negative urine pregnancy test is required for female participants of child bearing potential (>13 years of age).
  6. Patients must have adequate liver function as defined by AST or ALT <10x normal and a bilirubin <1.5mg/dl
  7. 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:

  1. Life expectancy <3 months
  2. Investigational Drugs: Patients who are currently receiving another investigational drug.
  3. Anti-cancer Agents: Patients who are currently receiving other anticancer agents.
  4. Infection: Patients who have an uncontrolled infection.
  5. Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study.
  6. Patients may not receive bisphosphonates (i.e. Zometa) within 7 days of start of therapy.
  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: NCT00486564

Locations
United States, Missouri
St. Louis University/Cardinal Glennon Childrens Medical Center
St. Louis, Missouri, United States, 63104
United States, Vermont
University of Vermont/Vermont Children's Hospital
Burlington, Vermont, United States, 05401
Sponsors and Collaborators
University of Vermont
St. Louis University
Investigators
Study Chair: Giselle Sholler, MD University of Vermont / Vermont Children's Hospital
  More Information

Publications:
Responsible Party: Giselle Sholler, MD, University of Vermont
ClinicalTrials.gov Identifier: NCT00486564     History of Changes
Other Study ID Numbers: V0610
Study First Received: June 12, 2007
Last Updated: October 22, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Vermont:
Treatment
Refractory or Relapsed

Additional relevant MeSH terms:
Neuroblastoma
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
Nifurtimox
Trypanocidal Agents
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 29, 2014