Clinical Trial: Irinotecan, Temozolomide, and Cefixime in Treating Young Patients With Recurrent or Resistant Neuroblastoma

This study is currently recruiting patients.

Sponsored by: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)

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 Treatment or Intervention Phase
Diarrhea
Drug Toxicity
disseminated neuroblastoma
recurrent neuroblastoma
 Drug: cefixime
 Drug: irinotecan
 Drug: temozolomide
 Procedure: antibiotic therapy
 Procedure: chemoprotection
 Procedure: chemosensitization/potentiation
 Procedure: chemotherapy
 Procedure: complications of therapy assessment/management
 Procedure: infection prophylaxis/management
 Procedure: supportive care/therapy
Phase I

MedlinePlus related topics:  Diarrhea;   Neuroblastoma;   Poisoning

Study Type: Interventional
Study Design: Treatment

Official Title: Phase I Study of Irinotecan, Temozolomide, and Cefixime in Pediatric Patients With Recurrent or Resistant High-Risk Neuroblastoma

Further Study Details: 

OBJECTIVES: Primary

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   -   30 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

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

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

Location and Contact Information


California
      Children's Hospital Los Angeles, Los Angeles,  California,  90027-0700,  United States; Recruiting
Judith G. Villablanca, MD  323-669-5654    jvillablanca@chla.usc.edu 

      Lucile Packard Children's Hospital at Stanford University Medical Center, Palo Alto,  California,  94304,  United States; Recruiting
Clare Twist, MD  650-723-5535 

      UCSF Comprehensive Cancer Center, San Francisco,  California,  94143,  United States; Recruiting
Katherine K. Matthay, MD  415-476-3831 

Ohio
      Cincinnati Children's Hospital Medical Center, Cincinnati,  Ohio,  45229-3039,  United States; Recruiting
John Peter Perentesis, MD  513-636-6090 

Pennsylvania
      Children's Hospital of Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States; Recruiting
John M. Maris, MD  215-590-2821    maris@email.chop.edu 

Texas
      Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital, Houston,  Texas,  77030-2399,  United States; Recruiting
Susan M. Blaney, MD  832-822-4586    sblaney@txccc.org 

Study chairs or principal investigators

Lars Martin Wagner, MD,  Study Chair,  Children's Hospital Medical Center - Cincinnati   
Katherine K. Matthay, MD,  University of California, San Francisco   

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Study ID Numbers:  CDR0000373759; NANT-2003-01; NCT00093353
Record last reviewed:  October 2004
Last Updated:  March 10, 2005
Record first received:  October 6, 2004
ClinicalTrials.gov Identifier:  NCT00093353
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08


Source: ClinicalTrials.gov
Cache Date: April 9, 2005