N2003-01: Irinotecan, Temozolomide, and Cefixime in Treating Young Patients With Recurrent or Resistant Neuroblastoma
NCT ID: NCT00093353
Last Updated: 2010-10-15
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1
30 participants
INTERVENTIONAL
2004-05-31
Brief Summary
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PURPOSE: This phase I trial is studying the side effects and best dose of irinotecan when given together with temozolomide and cefixime in treating young patients with recurrent or resistant neuroblastoma.
Detailed Description
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Primary
* Determine the maximum tolerated dose of oral irinotecan when administered with fixed-dose temozolomide and cefixime in pediatric patients with recurrent or resistant high-risk neuroblastoma.
* Determine the toxic effects of this regimen in these patients.
Secondary
* Determine the response rate in patients treated with this regimen.
* Determine the pharmacokinetics of this regimen in these patients.
* Correlate UGT1A1 genotype with the occurrence of dose-limiting diarrhea in patients treated with this regimen.
* Correlate BCRP genotype with pharmacokinetic phenotype in patients treated with this regimen.
* Correlate p53 status in tumor cells with response in patients treated with this regimen.
OUTLINE: This is a multicenter, dose-escalation study of irinotecan.
Patients receive oral cefixime once daily beginning 5 days before the start of fixed-dose temozolomide and irinotecan and continuing for the duration of the study. Patients also receive oral temozolomide once daily on days 1-5 and oral irinotecan once daily on days 1-5 and 8-12. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of irinotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A maximum of 12 patients are treated at the MTD.
Patients are followed for toxicity, response, and survival.
PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 1.25 years.
Conditions
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Study Design
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TREATMENT
Interventions
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cefixime
irinotecan hydrochloride
temozolomide
Eligibility Criteria
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Inclusion Criteria
* Histologically confirmed neuroblastoma AND/OR demonstration of tumor cells in the bone marrow with increased urinary catecholamines
* High-risk disease meeting 1 of the following criteria:
* Recurrent or progressive disease
* Resistant or refractory disease (i.e., never achieved a complete response to therapy AND never had new sites of disease or progression of initial sites)
* Measurable disease meeting at least 1 of the following criteria:
* Unidimensionally measurable tumor ≥ 20 mm by MRI, CT scan, or x-ray OR ≥ 10 mm by spiral CT scan\*
* At least 1 site with positive uptake by metaiodobenzylguanidine (MIBG) scan\*
* Bone marrow with tumor cells seen on routine morphology (not by NSE staining only) of bilateral aspirate AND/OR biopsy on 1 bone marrow sample NOTE: \*Patients who never experienced disease recurrence or progression must demonstrate viable neuroblastoma in a biopsy of either bone marrow or bone and/or soft tissue site (biopsy must be performed ≥ 4 weeks after completion of prior radiotherapy if lesion was irradiated)
PATIENT CHARACTERISTICS:
Age
* 1 to 30 at diagnosis
Performance status
* ECOG 0-2
Life expectancy
* At least 2 months
Hematopoietic
* Absolute neutrophil count ≥ 750/mm\^3
* Platelet count ≥ 75,000/mm\^3 (without transfusion)
* Hemoglobin ≥ 8.0 g/dL (transfusion allowed)
Hepatic
* SGPT and SGOT \< 5 times normal
* Bilirubin ≤ 1.5 times normal
Renal
* Creatinine ≤ 1.5 times normal for age
* No greater than 0.8 mg/dL (≤ 5 years of age)
* No greater than 1.0 mg/dL (6 to 10 years of age)
* No greater than 1.2 mg/dL (11 to 15 years of age)
* No greater than 1.5 mg/dL (\> 15 years of age)
Other
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No allergy to cephalosporins
* No active diarrhea
* No uncontrolled infection
PRIOR CONCURRENT THERAPY:
Biologic therapy
* See Chemotherapy
* Recovered from prior immunotherapy
* More than 3 weeks since prior biologic therapy and recovered
* More than 2 days since prior hematopoietic growth factors
* No concurrent epoetin alfa
* No concurrent prophylactic hematopoietic growth factors during the first treatment course
* No concurrent immunomodulating agents except steroids to control intracranial pressure
Chemotherapy
* Prior myeloablative therapy and autologous stem cell transplantation allowed
* No prior allogeneic stem cell transplantation
* More than 3 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered
* Prior temozolomide, irinotecan, or topotecan allowed
* No prior temozolomide and irinotecan as combination therapy
* No other concurrent chemotherapy
Endocrine therapy
* See Biologic therapy
Radiotherapy
* At least 6 weeks since prior large field radiotherapy (e.g., total body irradiation, craniospinal therapy, whole abdomen, total lung, or \> 50% bone marrow space) and recovered
* At least 4 weeks since prior radiotherapy to biopsied lesions (for study entry) and recovered
* At least 6 weeks since prior MIBG therapy
* Concurrent radiotherapy to painful lesions allowed provided the lesions are not used to assess treatment response
Surgery
* Not specified
Other
* No concurrent enzyme-inducing anticonvulsants (e.g., phenobarbital, phenytoin, or carbamazepine)
* No other concurrent anticancer agents
1 Year
30 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Children's Hospital Los Angeles
OTHER
Responsible Party
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Cincinnati Children's Hospital Medical Center
Principal Investigators
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Lars M. Wagner, MD
Role: STUDY_CHAIR
Children's Hospital Medical Center, Cincinnati
Katherine K. Matthay, MD
Role: PRINCIPAL_INVESTIGATOR
University of California, San Francisco
Locations
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Children's Hospital Los Angeles
Los Angeles, California, United States
Lucile Packard Children's Hospital at Stanford University Medical Center
Palo Alto, California, United States
UCSF Comprehensive Cancer Center
San Francisco, California, United States
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
Atlanta, Georgia, United States
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States
Indiana University Cancer Center
Indianapolis, Indiana, United States
Children's Hospital Boston
Boston, Massachusetts, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
Houston, Texas, United States
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States
Countries
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References
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Wagner LM, Villablanca JG, Stewart CF, Crews KR, Groshen S, Reynolds CP, Park JR, Maris JM, Hawkins RA, Daldrup-Link HE, Jackson HA, Matthay KK. Phase I trial of oral irinotecan and temozolomide for children with relapsed high-risk neuroblastoma: a new approach to neuroblastoma therapy consortium study. J Clin Oncol. 2009 Mar 10;27(8):1290-6. doi: 10.1200/JCO.2008.18.5918. Epub 2009 Jan 26.
Other Identifiers
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N2003-01
Identifier Type: OTHER
Identifier Source: secondary_id
CDR0000373759
Identifier Type: -
Identifier Source: org_study_id