N2003-01: Irinotecan, Temozolomide, and Cefixime in Treating Young Patients With Recurrent or Resistant Neuroblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00093353
Recruitment Status : Completed
First Posted : October 8, 2004
Last Update Posted : October 15, 2010
National Cancer Institute (NCI)
Information provided by:
Children's Hospital Los Angeles

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as irinotecan and temozolomide, work in different ways to stop tumor cells from dividing so they stop growing or die. Temozolomide may help irinotecan kill more tumor cells by making them more sensitive to the drug. Cefixime may be effective in preventing diarrhea that is caused by treatment with irinotecan.

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.

Condition or disease Intervention/treatment Phase
Diarrhea Drug/Agent Toxicity by Tissue/Organ Neuroblastoma Drug: cefixime Drug: irinotecan hydrochloride Drug: temozolomide Phase 1

Detailed Description:



  • 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.


  • 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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Primary Purpose: Treatment
Official Title: A Phase I Study Of Oral Irinotecan, Temozolomide, Cefixime In Children With Recurrent/Resistant High-Risk Neuroblastoma
Study Start Date : May 2004
Actual Primary Completion Date : July 2006

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   1 Year to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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)



  • 1 to 30 at diagnosis

Performance status

  • ECOG 0-2

Life expectancy

  • At least 2 months


  • Absolute neutrophil count ≥ 750/mm^3
  • Platelet count ≥ 75,000/mm^3 (without transfusion)
  • Hemoglobin ≥ 8.0 g/dL (transfusion allowed)


  • SGPT and SGOT < 5 times normal
  • Bilirubin ≤ 1.5 times normal


  • 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)


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No allergy to cephalosporins
  • No active diarrhea
  • No uncontrolled infection


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


  • 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


  • 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


  • Not specified


  • No concurrent enzyme-inducing anticonvulsants (e.g., phenobarbital, phenytoin, or carbamazepine)
  • No other concurrent anticancer agents

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00093353

United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027-0700
Lucile Packard Children's Hospital at Stanford University Medical Center
Palo Alto, California, United States, 94304
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94143
United States, Georgia
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
Atlanta, Georgia, United States, 30322
United States, Illinois
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60614
United States, Indiana
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202-5289
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0718
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
Houston, Texas, United States, 77030-2399
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Children's Hospital Los Angeles
National Cancer Institute (NCI)
Study Chair: Lars M. Wagner, MD Children's Hospital Medical Center, Cincinnati
Principal Investigator: Katherine K. Matthay, MD University of California, San Francisco

Publications of Results:
Responsible Party: Lars Wagner, M.D., Cincinnati Children's Hospital Medical Center Identifier: NCT00093353     History of Changes
Other Study ID Numbers: CDR0000373759
P01CA081403 ( U.S. NIH Grant/Contract )
N2003-01 ( Other Identifier: NANT Consortium )
First Posted: October 8, 2004    Key Record Dates
Last Update Posted: October 15, 2010
Last Verified: May 2009

Keywords provided by Children's Hospital Los Angeles:
drug/agent toxicity by tissue/organ
disseminated neuroblastoma
recurrent neuroblastoma

Additional relevant MeSH terms:
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Signs and Symptoms, Digestive
Signs and Symptoms
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents
Anti-Bacterial Agents
Anti-Infective Agents