SCH 66336 in Treating Children With Recurrent or Progressive Brain Tumors

RATIONALE: SCH 66336 may stop the growth of tumor cells by blocking the enzymes necessary for cancer cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of SCH 66336 in treating children with recurrent or progressive brain tumors.

OBJECTIVES:

* Determine the qualitative and quantitative toxicity of SCH 66336 in children with recurrent or progressive brain tumors.
* Estimate the maximum tolerated dose of this drug in these patients.
* Describe the pharmacokinetics of this drug with and without dexamethasone in these patients.
* Investigate the efficacy of this drug in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive oral SCH 66336 twice daily. Treatment repeats every 4 weeks for a total of 26 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 1-6 patients receive escalating doses of SCH 66336 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which it is predicted that 20% of patients may experience dose-limiting toxicity. An additional 6 patients are treated at the determined MTD.

Patients are followed within 30 days of the last administration of the study drug and then for up to 3 months.

PROJECTED ACCRUAL: Approximately 25 patients will be accrued for this study.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically confirmed recurrent or progressive (refractory) brain tumors

  * Histologic confirmation waived for brainstem gliomas
* Bone marrow involvement allowed if transfusion independent

PATIENT CHARACTERISTICS:

Age:

* 21 and under

Performance status:

* Lansky 60-100% OR
* Karnofsky 60-100%

Life expectancy:

* More than 8 weeks

Hematopoietic:

* See Disease Characteristics
* Absolute neutrophil count greater than 1,000/mm\^3
* Platelet count greater than 75,000/mm\^3
* Hemoglobin greater than 9 g/dL

Hepatic:

* Bilirubin no greater than upper limit of normal
* SGPT and SGOT less than 2.5 times normal
* Albumin greater than 3 g/dL
* PT/PTT no greater than 120% upper limit of normal
* No overt hepatic disease

Renal:

* Creatinine no greater than 1.5 times normal OR
* Glomerular filtration rate greater than 70 mL/min
* No overt renal disease

Cardiovascular:

* No overt cardiac disease

Pulmonary:

* No overt pulmonary disease

Other:

* Neurologic deficits allowed if stable for at least 1 week prior to study
* More than 3rd percentile weight for height
* Able to swallow pills
* No uncontrolled infection
* No known or suspected allergy to poloxamer 188, croscarmellose sodium, silicon dioxide, or magnesium stearate I
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for up to 10 weeks after study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* More than 6 months since prior bone marrow transplantation
* More than 1 week since prior growth factors

Chemotherapy:

* At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered

Endocrine therapy:

* Concurrent dexamethasone allowed if on stable dose for at least 1 week prior to study
* Concurrent oral contraceptives or other hormonal contraceptive methods allowed

Radiotherapy:

* More than 6 weeks since prior substantial bone marrow radiotherapy
* More than 3 months since prior craniospinal radiotherapy (more than 24 Gy) or total body irradiation
* More than 2 weeks since prior focal radiotherapy for symptomatic metastatic sites

Surgery:

* Not specified

Other:

* No concurrent enzyme-inducing anticonvulsant drugs
* No other concurrent anticancer or experimental drug therapy