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Safety Study of Nifurtimox for Relapsed or Refractory Neuroblastoma

Primary Purpose

Neuroblastoma

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Nifurtimox

About this trial

This is an interventional treatment trial for Neuroblastoma focused on measuring Treatment, Refractory or Relapsed

Eligibility Criteria

undefined - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age: 0-21 years at the time of study entry.
Diagnosis: Histologic verification of neuroblastoma at original diagnosis or relapse.
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).
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).
Patients must have adequate liver function as defined by AST or ALT <10x normal and a bilirubin <1.5mg/dl
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 <3 months
Investigational Drugs: Patients who are currently receiving another investigational drug.
Anti-cancer Agents: Patients who are currently receiving other anticancer agents.
Infection: Patients who have an uncontrolled infection.
Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study.
Patients may not receive bisphosphonates (i.e. Zometa) within 7 days of start of therapy.

Sites / Locations

St. Louis University/Cardinal Glennon Childrens Medical Center
University of Vermont/Vermont Children's Hospital

Outcomes

Primary Outcome Measures

Test the safety of nifurtimox in children with relapsed or refractory neuroblastoma alone and in combination with cyclophosphamide and topotecan.

Secondary Outcome Measures

To evaluate the pharmacokinetic profile of nifurtimox alone and in combination with cyclophosphamide and topotecan.

To determine the response rate to treatment with nifurtimox combined with cyclophosphamide/topotecan

Full Information

NCT ID

NCT00486564

First Posted

June 12, 2007

Last Updated

October 22, 2009

Sponsor

University of Vermont

Collaborators

St. Louis University

1. Study Identification

Unique Protocol Identification Number

NCT00486564

Brief Title

Safety Study of Nifurtimox for Relapsed or Refractory Neuroblastoma

Official Title

A Phase I Trial of Nifurtimox for Relapsed or Refractory Neuroblastoma

Study Type

Interventional

2. Study Status

Record Verification Date

October 2009

Overall Recruitment Status

Completed

Study Start Date

November 2006 (undefined)

Primary Completion Date

November 2007 (Actual)

Study Completion Date

June 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

University of Vermont

Collaborators

St. Louis University

4. Oversight

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Neuroblastoma

Keywords

Treatment, Refractory or Relapsed

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

Nifurtimox

Intervention Description

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

Primary Outcome Measure Information:

Title

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 Measure Information:

Title

To evaluate the pharmacokinetic profile of nifurtimox alone and in combination with cyclophosphamide and topotecan.

Time Frame

3 months

Title

To determine the response rate to treatment with nifurtimox combined with cyclophosphamide/topotecan

Time Frame

3 months

10. Eligibility

Sex

All

Maximum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age: 0-21 years at the time of study entry. Diagnosis: Histologic verification of neuroblastoma at original diagnosis or relapse. 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). 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). Patients must have adequate liver function as defined by AST or ALT <10x normal and a bilirubin <1.5mg/dl 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 <3 months Investigational Drugs: Patients who are currently receiving another investigational drug. Anti-cancer Agents: Patients who are currently receiving other anticancer agents. Infection: Patients who have an uncontrolled infection. Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study. Patients may not receive bisphosphonates (i.e. Zometa) within 7 days of start of therapy.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Giselle Sholler, MD

Organizational Affiliation

University of Vermont / Vermont Children's Hospital

Official's Role

Study Chair

Facility Information:

Facility Name

St. Louis University/Cardinal Glennon Childrens Medical Center

City

St. Louis

State/Province

Missouri

ZIP/Postal Code

63104

Country

United States

Facility Name

University of Vermont/Vermont Children's Hospital

City

Burlington

State/Province

Vermont

ZIP/Postal Code

05401

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

17023833

Citation

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.

Results Reference

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Safety Study of Nifurtimox for Relapsed or Refractory Neuroblastoma

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