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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Children's Hospital Los Angeles
ClinicalTrials.gov Identifier:
NCT00093353
First received: October 6, 2004
Last updated: October 14, 2010
Last verified: May 2009
  Purpose

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

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Phase I Study Of Oral Irinotecan, Temozolomide, Cefixime In Children With Recurrent/Resistant High-Risk Neuroblastoma

Resource links provided by NLM:


Further study details as provided by Children's Hospital Los Angeles:

Estimated Enrollment: 30
Study Start Date: May 2004
Primary Completion Date: July 2006 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   1 Year to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00093353

Locations
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
Investigators
Study Chair: Lars M. Wagner, MD Children's Hospital Medical Center, Cincinnati
Principal Investigator: Katherine K. Matthay, MD University of California, San Francisco
  More Information

Additional Information:
Publications:
Responsible Party: Lars Wagner, M.D., Cincinnati Children's Hospital Medical Center
ClinicalTrials.gov Identifier: NCT00093353     History of Changes
Other Study ID Numbers: CDR0000373759, P01CA081403, N2003-01
Study First Received: October 6, 2004
Last Updated: October 14, 2010
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Diarrhea
Neuroblastoma
Signs and Symptoms, Digestive
Signs and Symptoms
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Cefixime
Temozolomide
Dacarbazine
Irinotecan
Camptothecin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on July 31, 2014