Safety Study of Nifurtimox for Relapsed or Refractory Neuroblastoma

• ClinicalTrials.gov Identifier: NCT00486564
• Recruitment Status: Completed
• First Posted: June 14, 2007
• Last Update Posted: October 23, 2009
• Sponsor: University of Vermont
• Collaborator: St. Louis University
• Information provided by: University of Vermont

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Neuroblastoma	Drug: Nifurtimox	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Trial of Nifurtimox for Relapsed or Refractory Neuroblastoma
• Study Start Date: November 2006
• Actual Primary Completion Date: November 2007
• Actual Study Completion Date: June 2009

Arms and Interventions

Intervention Details:

• Drug: Nifurtimox
  Escalating dose by cohort starting at 20mg/kg/day. PO drug taken TID.

Outcome Measures

Primary Outcome Measures :

1. Test the safety of nifurtimox in children with relapsed or refractory neuroblastoma alone and in combination with cyclophosphamide and topotecan. [ Time Frame: 3 months ]

Secondary Outcome Measures :

1. To evaluate the pharmacokinetic profile of nifurtimox alone and in combination with cyclophosphamide and topotecan. [ Time Frame: 3 months ]
2. To determine the response rate to treatment with nifurtimox combined with cyclophosphamide/topotecan [ Time Frame: 3 months ]

Eligibility Criteria

• Ages Eligible for Study: up to 21 Years (Child, Adult)
• Sexes Eligible for Study: All
• 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

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:

Saulnier Sholler GL, Kalkunte S, Greenlaw C, McCarten K, Forman E. Antitumor activity of nifurtimox observed in a patient with neuroblastoma. J Pediatr Hematol Oncol. 2006 Oct;28(10):693-5. doi: 10.1097/01.mph.0000212994.56812.f2.

• Responsible Party: Giselle Sholler, MD, University of Vermont
• ClinicalTrials.gov Identifier: NCT00486564
• Other Study ID Numbers: V0610
• First Posted: June 14, 2007
• Last Update Posted: October 23, 2009
• Last Verified: October 2009

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