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

October 14, 2010 updated by: Children's Hospital Los Angeles

A Phase I Study Of Oral Irinotecan, Temozolomide, Cefixime In Children With Recurrent/Resistant High-Risk Neuroblastoma

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

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.

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90027-0700
        • Children's Hospital Los Angeles
      • Palo Alto, California, United States, 94304
        • Lucile Packard Children's Hospital at Stanford University Medical Center
      • San Francisco, California, United States, 94143
        • UCSF Comprehensive Cancer Center
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
    • Illinois
      • Chicago, Illinois, United States, 60614
        • Children's Memorial Hospital - Chicago
    • Indiana
      • Indianapolis, Indiana, United States, 46202-5289
        • Indiana University Cancer Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Children's Hospital Boston
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-0718
        • University of Michigan Comprehensive Cancer Center
    • Ohio
      • Cincinnati, Ohio, United States, 45229-3039
        • Cincinnati Children's Hospital Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
    • Texas
      • Houston, Texas, United States, 77030-2399
        • Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
    • Washington
      • Seattle, Washington, United States, 98105
        • Children's Hospital and Regional Medical Center - Seattle

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 months to 28 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital Los Angeles

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Lars M. Wagner, MD, Children's Hospital Medical Center, Cincinnati

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2004

Primary Completion (Actual)

July 1, 2006

Study Registration Dates

First Submitted

October 6, 2004

First Submitted That Met QC Criteria

October 7, 2004

First Posted (Estimate)

October 8, 2004

Study Record Updates

Last Update Posted (Estimate)

October 15, 2010

Last Update Submitted That Met QC Criteria

October 14, 2010

Last Verified

May 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000373759
  • P01CA081403 (U.S. NIH Grant/Contract)
  • N2003-01 (Other Identifier: NANT Consortium)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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