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

NCT00093353 | Completed Phase 1 DMC

• 3 other identifiers: CDR0000373759P01CA081403N2003-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 13

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.

Conditions

Diarrhea; Neuroblastoma; Drug/Agent Toxicity by Tissue/Organ

Keywords

diarrhea; drug/agent toxicity by tissue/organ; disseminated neuroblastoma; recurrent neuroblastoma

Interventions

cefixime DRUG

irinotecan hydrochloride DRUG

temozolomide DRUG

Eligibility Criteria

• Age: 1 Year - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• New Approaches to Neuroblastoma Therapy Consortium: lead

Study Sites (13)

Children's Hospital Los Angeles

Los Angeles, California, 90027-0700, United States

Location

Lucile Packard Children's Hospital at Stanford University Medical Center

Palo Alto, California, 94304, United States

Location

UCSF Comprehensive Cancer Center

San Francisco, California, 94143, United States

Location

AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus

Atlanta, Georgia, 30322, United States

Location

Children's Memorial Hospital - Chicago

Chicago, Illinois, 60614, United States

Location

Indiana University Cancer Center

Indianapolis, Indiana, 46202-5289, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109-0718, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital

Houston, Texas, 77030-2399, United States

Location

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, 98105, United States

Location

Related Publications (1)

• 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.

  PMID: 19171709 RESULT

MeSH Terms

Conditions

Diarrhea; Drug-Related Side Effects and Adverse Reactions; Neuroblastoma

Interventions

Cefixime; Irinotecan; Temozolomide

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Chemically-Induced Disorders; 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

Intervention Hierarchy (Ancestors)

Cefotaxime; Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Lars M. Wagner, MD

  Children's Hospital Medical Center, Cincinnati

  STUDY CHAIR

• Katherine K. Matthay, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2004
• First Posted: October 8, 2004
• Study Start: May 1, 2004
• Primary Completion: July 1, 2006
• Last Updated: April 14, 2026

Record last verified: 2009-05

Locations

US (13)