A Phase I Study of Temozolomide, Oral Irinotecan, and Vincristine for Children With Refractory Solid Tumors

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed* malignant solid tumor, including brain tumor, at original
diagnosis or relapse

- Refractory disease NOTE: *Histologic confirmation not required for intrinsic
brain stem tumors

- Measurable or evaluable disease

- No known curative therapy OR therapy proven to prolong survival with an acceptable
quality of life exists

- No known bone marrow metastases

PATIENT CHARACTERISTICS:

Age

- 1 to 21

Performance status

- Lansky 50-100% (for patients ≤ 10 years of age)

- Karnofsky 50-100% (for patients > 10 years of age)

Life expectancy

- Not specified

Hematopoietic

- Absolute neutrophil count ≥ 1,000/mm^3

- Platelet count ≥ 100,000/mm^3 (transfusion independent)

- Hemoglobin ≥ 8.0 g/dL (RBC transfusions allowed)

Hepatic

- ALT ≤ 110 U/L (upper limit of normal [ULN] for ALT is 45 U/L)

- Bilirubin ≤ 1.5 times ULN

- Albumin ≥ 2 g/dL

Renal

- Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR

- Creatinine based on age as follows:

- No greater than 0.8 mg/dL (for patients ≤ 5 years of age)

- No greater than 1.0 mg/dL (for patients 6 to 10 years of age)

- No greater than 1.2 mg/dL (for patients 11 to 15 years of age)

- No greater than 1.5 mg/dL (for patients > 15 years of age)

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Neurologic deficits in patients with CNS tumors must be stable for ≥ 1 week prior to
study entry

- No uncontrolled infection

- No documented allergy to cephalosporins or dacarbazine

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Recovered from prior immunotherapy

- At least 3 months since prior stem cell transplantation or rescue without total-body
irradiation

- No evidence of active graft-versus-host disease

- At least 7 days since prior antineoplastic biologic agents

- At least 7 days since prior hematopoietic growth factors

- No concurrent biologic therapy or immunotherapy

- No concurrent prophylactic filgrastim (G-CSF) during the first course of study
treatment

Chemotherapy

- Recovered from prior chemotherapy

- Prior temozolomide, vincristine, irinotecan, or topotecan allowed

- No prior coadministration of temozolomide and irinotecan

- No disease progression during treatment with either irinotecan or temozolomide

- More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for
nitrosoureas)

- No other concurrent chemotherapy

Endocrine therapy

- Patients with CNS tumors must be on a stable or decreasing dose of dexamethasone for
≥ 7 days prior to study entry

Radiotherapy

- Recovered from prior radiotherapy

- At least 6 months since prior total-body irradiation, craniospinal radiotherapy, or
radiotherapy to ≥ 50% of the pelvis

- At least 6 weeks since other prior substantial bone marrow radiotherapy

- At least 2 weeks since prior local palliative radiotherapy (small port)

- No concurrent radiotherapy

Surgery

- Not specified

Other

- No other concurrent investigational drugs

- No other concurrent anticancer therapy

- No concurrent enzyme-inducing anticonvulsants, including any of the following:

- Phenobarbital

- Phenytoin

- Carbamazepine

- Oxcarbazepine

- No concurrent administration of any of the following:

- Rifampin

- Voriconazole

- Itraconazole

- Ketoconazole

- Aprepitant

- Hypericum perforatum (St. John's wort)

- No concurrent treatment for clostridium difficile infection