• Toxicity [ Designated as safety issue: Yes ]
• Pharmacokinetics [ Designated as safety issue: No ]
• Pharmacodynamics [ Designated as safety issue: No ]

• Toxicity
• Pharmacokinetics
• Pharmacodynamics

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase II trial is studying irinotecan to see how well it works in treating children with refractory solid tumors.

OBJECTIVES:

• Determine the efficacy of irinotecan in children with refractory CNS or solid tumors.
• Assess the toxicity, pharmacokinetics, and pharmacodynamics of this regimen in this patient population.
• Determine patient UGT1A1 genotype and correlate genotype with toxicity and pharmacokinetic parameters of this regimen in these patients.

OUTLINE: Patients are stratified according to type of solid tumor (Ewings/PNET vs neuroblastoma vs osteosarcoma vs rhabdomyosarcoma vs other solid tumors excluding lymphomas and brain tumors) or brain tumor (medulloblastoma/PNET vs brain stem glioma vs ependymoma vs other CNS tumors).

Patients receive irinotecan IV over 60 minutes on days 1-5. Treatment repeats every 3 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 6 months for 4 years and then annually thereafter until death or until patient enters another POG study.

PROJECTED ACCRUAL: A total of 225 patients will be accrued for this study.

• Brain and Central Nervous System Tumors
• Neuroblastoma
• Sarcoma
• Unspecified Childhood Solid Tumor, Protocol Specific

• Thompson PA, Gupta M, Rosner GL, Yu A, Barrett J, Bomgaars L, Bernstein ML, Blaney SM, Mondick J. Pharmacokinetics of irinotecan and its metabolites in pediatric cancer patients: a report from the children's oncology group. Cancer Chemother Pharmacol. 2008 Feb 16; [Epub ahead of print]
• Bomgaars LR, Bernstein M, Krailo M, Kadota R, Das S, Chen Z, Adamson PC, Blaney SM. Phase II trial of irinotecan in children with refractory solid tumors: a Children's Oncology Group Study. J Clin Oncol. 2007 Oct 10;25(29):4622-7.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed CNS or solid tumors recurrent or refractory to standard therapy

  • Solid tumors:

    • Neuroblastoma
    • Ewing's Sarcoma/peripheral primitive neuroectodermal tumor (PNET)
    • Osteosarcoma
    • Rhabdomyosarcoma
    • Other extracranial solid tumors

  • CNS tumors:

    • Medulloblastoma/PNET
    • Ependymoma
    • Brain stem glioma
    • Other CNS tumor
    • Intrinsic brain stem tumor (biopsy required only if previously treated with radiosurgery)
    • Classic optic glioma (histologic requirement waived)

• Measurable disease by imaging studies

  • No lesions assessable only by radionuclide scan
• Previously irradiated lesions used to evaluate tumor response must show evidence of an interim increase in size

PATIENT CHARACTERISTICS:

Age:

• 1 to 21

Performance status:

• Karnofsky 50-100% if more than 10 years old OR
• Lansky 50-100% if 10 years or younger

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Absolute neutrophil count greater than 1,000/mm^3
• Platelet count greater than 100,000/mm^3
• Hemoglobin greater than 8 mg/dL
• Inadequate peripheral blood counts due to bone marrow infiltration allowed

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• SGPT less than 5 times normal

Renal:

• Creatinine normal
• Glomerular filtration rate at least 70 mL/min

Other:

• No severe uncontrolled infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 3 weeks since prior immunotherapy and recovered
• No concurrent biologic therapy

Chemotherapy:

• At least 3 weeks since prior chemotherapy (8 weeks since prior nitrosoureas) and recovered
• No more than 2 prior chemotherapy regimens
• No other concurrent chemotherapy
• Prior topotecan allowed
• No prior irinotecan

Endocrine therapy:

• Concurrent dexamethasone for brain tumor patients allowed if on a stable or decreasing dose for at least 2 weeks prior to study
• At least 3 weeks since prior endocrine therapy
• No other concurrent endocrine therapy

Radiotherapy:

• See Disease Characteristics
• At least 8 weeks since prior extended radiotherapy (including evaluable lesions) and recovered
• No prior total body radiotherapy
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics

Other:

• At least 3 weeks since prior investigational agents
• No other concurrent investigational agents
• No concurrent anticonvulsants
• No concurrent medications that would interfere with the P-450 enzyme system function (e.g., erythromycin, cimetidine, fluconazole)