RATIONALE: Gefitinib may stop the growth of cancer cells by blocking the enzymes necessary for tumor cell growth.

PURPOSE: Phase I trial to study the effectiveness of gefitinib in treating children who have refractory solid tumors.

OBJECTIVES:

• Determine the maximum tolerated dose of gefitinib in children with refractory solid tumors.
• Determine the dose-limiting toxicity of this drug in these patients.
• Determine the pharmacokinetics of this drug in these patients.
• Determine, preliminarily, the antitumor activity of this drug in these patients.
• Correlate the pharmacogenetic polymorphisms of this drug with pharmacokinetics and pharmacodynamics in these patients.

OUTLINE: This is a dose-escalation, multicenter study. If myelosuppression is found to be the dose-limiting toxicity, patients are stratified according to prior therapy (more than 2 multiagent chemotherapy regimens or radiotherapy to more than 20% of the bone marrow or stem cell transplantation with or without total body irradiation vs more than 2 single-agent phase I or phase II agents) and extent of disease (bone marrow involvement vs meeting none of the stratum I criteria).

Patients receive oral gefitinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of gefitinib 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.

PROJECTED ACCRUAL: Approximately 3-45 patients will be accrued for this study.

• Jimeno A, Daw NC, Amador ML, Cusatis G, Kulesza P, Krailo M, Ingle AM, Blaney SM, Adamson P, Hidalgo M. Analysis of biologic surrogate markers from a Children's Oncology Group Phase I trial of gefitinib in pediatric patients with solid tumors. Pediatr Blood Cancer. 2006 Jan 19; [Epub ahead of print]
• Daw NC, Furman WL, Stewart CF, Iacono LC, Krailo M, Bernstein ML, Dancey JE, Speights RA, Blaney SM, Croop JM, Reaman GH, Adamson PC; Children's Oncology Group. Phase I and pharmacokinetic study of gefitinib in children with refractory solid tumors: a Children's Oncology Group Study. J Clin Oncol. 2005 Sep 1;23(25):6172-80.

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumor at original diagnosis
• Refractory to conventional therapy and other therapies of higher priority according to the COG Phase I/II priority list or no conventional therapy exists
• No primary CNS tumors or known metastases to the CNS

PATIENT CHARACTERISTICS:

Age:

• Under 22

Performance status:

• Karnofsky 50-100% (over 10 years of age) OR
• Lansky 50-100% (10 years of age and under)

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,000/mm^3
• Platelet count at least 50,000/mm^3 (transfusion independent)
• Hemoglobin at least 8.0 g/dL (RBC transfusion allowed)

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• ALT no greater than 3 times ULN
• Albumin at least 2 g/dL

Renal:

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

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 6 months since prior allogeneic stem cell transplantation (SCT)

  • No evidence of active graft-versus-host disease
• At least 1 week since prior biologic agents
• At least 1 week since prior hematopoietic growth factors
• Recovered from prior immunotherapy

Chemotherapy:

• At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered

Endocrine therapy:

• No concurrent tamoxifen

Radiotherapy:

• At least 2 weeks since prior local palliative (small port) radiotherapy
• At least 6 months since prior craniospinal radiotherapy or radiotherapy to 50% or more of the pelvis (6 weeks for radiotherapy to other substantial amount of bone marrow)
• Recovered from prior radiotherapy

Surgery:

• Not specified

Other:

• No concurrent drugs with known corneal toxicity (e.g., chlorpromazine, amiodarone, or chloroquine)
• No concurrent enzyme-activating anticonvulsants
• No concurrent proton pump inhibitors or H_2 blockers within 4 hours of gefitinib administration