Study of Nifurtimox to Treat Refractory or Relapsed Neuroblastoma or Medulloblastoma
This study is currently recruiting participants.
Verified April 2013 by Van Andel Research Institute
Sponsor:
Giselle Sholler
Collaborator:
Bayer
Information provided by (Responsible Party):
Giselle Sholler, Van Andel Research Institute
ClinicalTrials.gov Identifier:
NCT00601003
First received: January 14, 2008
Last updated: April 5, 2013
Last verified: April 2013
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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 Van Andel Research Institute:
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: | January 2018 |
| Estimated Primary Completion Date: | January 2014 (Final data collection date for primary outcome measure) |
Intervention Details:
Detailed Description:
-
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
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00601003
Contacts
| Contact: Genevieve Bergendahl, RN | 616-234-5707 | genevieve.bergendahl@vai.org |
| Contact: Giselle Sholler, MD | giselle.sholler@vai.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: Sherell Thornton-Thompson Sthornt@ccmckids.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, 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: Samuel Walford, MA 980-442-2364 samuel.walford@carolinashealthcare.org | |
| Principal Investigator: Joel Kaplan, 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 | Van Andle Research Institute |
More Information
Additional Information:
No publications provided
| Responsible Party: | Giselle Sholler, Study Chair, Van Andel Research Institute |
| ClinicalTrials.gov Identifier: | NCT00601003 History of Changes |
| Other Study ID Numbers: | V0706 |
| Study First Received: | January 14, 2008 |
| Last Updated: | April 5, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Medulloblastoma Neuroblastoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neuroectodermal Tumors, Primitive Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neuroectodermal Tumors, Primitive, Peripheral Cyclophosphamide Topotecan Nifurtimox |
Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antirheumatic Agents Therapeutic Uses Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Trypanocidal Agents Antiprotozoal Agents Antiparasitic Agents Anti-Infective Agents |
ClinicalTrials.gov processed this record on June 18, 2013