A Phase I Study of Valproic Acid in Children With Recurrent/Progressive Solid Tumors Including CNS Tumors

Inclusion Criteria

DISEASE CHARACTERISTICS:

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

- Recurrent or refractory disease NOTE: *Histologic confirmation not required for
intrinsic brain stem or optic pathway tumors

- Measurable or evaluable disease, defined by 1 of the following criteria:

- Any unidimensionally measurable lesion ≥ 10 mm by standard MRI or CT scan for
either solid or CNS tumors

- At least 1 nonmeasurable lesion that is evaluable by nuclear medicine,
immunocytochemistry, tumor markers, cerebrospinal fluid cytology, or other
reliable measures

- No known curative therapy exists

- No documented tumor involvement in the bone marrow

PATIENT CHARACTERISTICS:

Age

- 2 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 (transfusions allowed)

Hepatic

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

- ALT ≤ 110 (ULN for this study is 45 U/L)

- 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 over 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 before
study entry

- No uncontrolled infection

- No known urea cycle disorders or other metabolic disorders

- No other condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Recovered from prior immunotherapy

- At least 7 days since prior hematopoietic growth factors that support platelet or WBC
number or function

- At least 7 days since prior antineoplastic biologic agents

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

- No evidence of active graft vs host disease

- No other concurrent anticancer biologic therapy or immunotherapy

Chemotherapy

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

- No other concurrent anticancer chemotherapy

Endocrine therapy

- Patients with CNS tumors must be on a stable or decreasing dose of dexamethasone for
the past 7 days

Radiotherapy

- See Biologic therapy

- 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 small port radiotherapy

- No concurrent anticancer radiotherapy

Surgery

- Not specified

Other

- No other concurrent investigational agents

- No other concurrent anticancer agents

- No other concurrent anticonvulsants

- Patients receiving valproic acid (VPA) before study entry must have a total
trough VPA concentration < 100 mcg/mL within the past 7 days