A Phase II Study of Irinotecan + Temozolomide in Children With Recurrent Neuroblastoma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed neuroblastoma AND/OR demonstration of tumor cells in the
bone marrow with increased urinary catecholamines at initial diagnosis

- Patients with elevated catecholamines only are not eligible

- Meets 1 of the following criteria:

- Recurrent disease following aggressive, multidrug, frontline chemotherapy,
defined as chemotherapy given with ≥ 2 agents, including an alkylating agent and
a platinum-containing compound

- Resistant/refractory disease during aggressive, multidrug, frontline
chemotherapy

- Must meet 1 of the following criteria for documentation of disease:

- Unidimensionally measurable tumor ≥ 20 mm by MRI, CT scan, or x-ray OR ≥ 10 mm
by spiral CT scan within 4 weeks prior to study entry

- Patients with residual stable tumor upon completion of frontline therapy
must undergo biopsy to document presence of a viable neuroblastoma

- If the measurable target lesion was previously radiated, a biopsy must be
performed ≥ 4 weeks after radiation was completed AND the biopsy must
demonstrate viable neuroblastoma

- MIBG scan with positive uptake at ≥ 1 site within 4 weeks prior to study entry

- Patients with residual stable MIBG-positive lesions upon completion of
frontline therapy must undergo biopsy to document presence of viable
neuroblastoma

- If the patient has only 1 MIBG-positive lesion, and that lesion was
previously radiated, a biopsy must be performed ≥ 4 weeks after radiation
was completed AND the biopsy must demonstrate viable neuroblastoma

- Bone marrow with tumor cells on routine morphology (not by neuron-specific
enolase staining only) of bilateral aspirate and/or biopsy on 1 bone marrow
sample within 2 weeks prior to study entry

- No extensive marrow disease

- No myelodysplastic syndrome

PATIENT CHARACTERISTICS:

- Karnofsky performance status (PS) 50-100% (for patients > 16 years of age) OR Lansky
PS 50-100% (for patients ≤ 16 years of age)

- Life expectancy ≥ 8 weeks

- Absolute neutrophil count ≥ 750/mm^3

- Platelet count ≥ 75,000/mm^3 (transfusion independent)

- Hemoglobin ≥ 8.5 mg/dL (transfusion allowed)

- Creatinine adjusted according to age as follows:

- No greater than 0.4 mg/dL (≤ 5 months)

- No greater than 0.5 mg/dL (6 months -11 months)

- No greater than 0.6 mg/dL (1 year-23 months)

- No greater than 0.8 mg/dL (2 years-5 years)

- No greater than 1.0 mg/dL (6 years-9 years)

- No greater than 1.2 mg/dL (10 years-12 years)

- No greater than 1.4 mg/dL (13 years and over [female])

- No greater than 1.5 mg/dL (13 years to 15 years [male])

- No greater than 1.7 mg/dL (16 years and over [male]) OR

- Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min

- Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age

- ALT < 2.5 times ULN for age

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Seizure disorder allowed provided seizures are well controlled on non-EIAC medication

- No active diarrhea or uncontrolled infection

- No other malignancy, including secondary malignancy

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Prior front-line therapy (e.g., surgery, chemotherapy, immunotherapy, radiotherapy,
or retinoids) allowed

- Recovered from prior therapy

- More than 4 weeks since prior radiation therapy to the site of any lesion that will
be identified as a target lesion to measure tumor response

- At least 2 weeks since prior myelosuppressive therapy (4 weeks for nitrosourea)

- At least 1 week since prior therapy with an antineoplastic biologic agent or retinoid

- At least 1 week since prior growth factors

- At least 1 week since prior and no other concurrent anticancer agents

- At least 1 week since prior and no concurrent enzyme-inducing anticonvulsants (EIAC),
including phenytoin, phenobarbital, valproic acid, or carbamazepine

- Concurrent gabapentin or levetiracetum allowed

- Concurrent palliative radiation therapy to sites not used to measure tumor response
allowed

- No prior allogeneic stem cell transplantation (SCT)

- Prior autologus SCT allowed

- No prior second-line chemotherapy for relapsed or refractory disease

- No concurrent immunomodulating agents

- Concurrent steroids for transfusion/infusion reactions or for treatment of edema
associated with CNS lesions allowed