• Maximum tolerated dose [ Designated as safety issue: Yes ]
• Dose-limiting toxicity [ Designated as safety issue: Yes ]
• Recommended phase II dose [ Designated as safety issue: Yes ]

• Metabolism [ Designated as safety issue: No ]
• Pharmacokinetics [ Designated as safety issue: No ]
• Pharmacodynamics [ Designated as safety issue: No ]
• Antineoplastic activity [ Designated as safety issue: No ]

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

PURPOSE: This phase I trial is studying the side effects and best dose of XK469 in treating patients with advanced neuroblastoma.

OBJECTIVES:

• Determine the maximum tolerated dose, recommended phase II dose, and dose-limiting toxicity of R(+)XK469 in two different dosing schedules in patients with advanced neuroblastoma.
• Determine the safety of this drug in these patients.
• Determine the tolerance to this drug in these patients.
• Determine the pharmacokinetics and pharmacodynamics of this drug and its metabolites in these patients.
• Determine, preliminarily, any antineoplastic activity of this drug in these patients.

OUTLINE: This is a dose-escalation study.

• Schedule A: Patients receive R(+)XK469 IV over 30 minutes on days 1, 3, and 5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of R(+)XK469 until the recommended phase II dose or maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued and treated at the recommended phase II dose (for a maximum of 20 patients treated at that dose).

• Schedule B: Once the recommended phase II dose is determined on schedule A, additional patients are accrued and receive escalating doses of R(+)XK469 IV over 30-60 minutes on day 1, beginning at a reduced dose. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Dose escalation continues as in schedule A.

PROJECTED ACCRUAL: Approximately 85 patients will be accrued for this study within 2.5-3.5 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed high-risk neuroblastoma that has relapsed or is refractory to standard therapy

• No active brain metastases

  • Previously treated brain metastases allowed if there is no requirement for corticosteroids or anticonvulsants

PATIENT CHARACTERISTICS:

Age:

• 5 to 20 years old

Performance status:

• Karnofsky performance status 70-100% or Lansky score ≥ 70 for your pediatric patients

Life expectancy:

• More than 3 months

Hematopoietic:

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin normal (unless due to documented Gilbert's syndrome)

Renal:

• Creatinine less than 1.5 times upper limit of normal

Cardiovascular:

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other concurrent uncontrolled illness that would preclude study participation
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study participation
• No prior allergic reaction to compounds of similar chemical or biological composition to study drug (e.g., flurbiprofen or ibuprofen)
• No HIV-positive patients

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent biologic agents

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
• No other concurrent chemotherapy

Endocrine therapy:

• See Disease Characteristics

Radiotherapy:

• At least 4 weeks since prior radiotherapy
• No concurrent palliative radiotherapy

Surgery:

• Not specified

Other:

• See Disease Characteristics
• Recovered from all prior therapy
• No other concurrent investigational agents
• No concurrent commercial agents or therapies directed at malignancy
• No concurrent combination anti-retroviral therapy for HIV-positive patients