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

• Status: Completed
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Children's Hospital Los Angeles
• Collaborator: National Cancer Institute (NCI)
• Treatments: Camptothecin; Cefixime; Dacarbazine; Irinotecan; Temozolomide

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