Temozolomide and O6-benzylguanine in Treating Children With Solid Tumors

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining temozolomide and O6-benzylguanine in treating children who have solid tumors that have not responded to previous therapy.

OBJECTIVES:

* Determine the maximum tolerated dose of temozolomide administered with a biologically active dose of O6-benzylguanine (O6-BG) in children with refractory solid tumors.
* Determine the dose-limiting toxicity and the toxicity profile of this combination in these patients.
* Assess the plasma pharmacokinetics of O6-BG and its active metabolite, 8-oxo-O6-BG, in these patients.
* Assess the plasma pharmacokinetics of this combination in these patients.
* Correlate levels of alanine-glyoxylate aminotransferase in peripheral blood mononuclear cells with the degree of hematologic toxicity of this combination in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive O6-benzylguanine (O6-BG) IV over 1 hour followed 30 minutes later by oral temozolomide daily for 5 days. Treatment continues every 28 days for up to 12 courses in the absence of unacceptable toxicity or disease progression.

Sequential dose escalation of O6-BG is followed by sequential dose escalation of temozolomide. Cohorts of 3-6 patients receive escalating doses of O6-BG and temozolomide until the maximum tolerated dose (MTD) of each is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 6 patients experience dose-limiting toxicity.

Quality of life is assessed at baseline and prior to courses 1, 3, 6, 8, and 12.

PROJECTED ACCRUAL: A total of 21-48 patients will be accrued for this study within 1-2 years.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically confirmed solid tumor refractory to standard therapy and for which no potentially curative therapy exists, including, but not limited to:

  * Rhabdomyosarcoma and other soft tissue sarcomas
  * Ewing's family of tumors
  * Osteosarcoma
  * Neuroblastoma
  * Wilms' tumor
  * Hepatic tumors
  * Germ cell tumors
  * Primary brain tumor
* Histological confirmation may be waived for brainstem or optic gliomas
* Measurable or evaluable disease
* Evidence of progressive disease on prior chemotherapy or radiotherapy or persistent disease after prior surgery

PATIENT CHARACTERISTICS:

Age:

* 21 and under

Performance status:

* ECOG 0-2

Life expectancy:

* At least 8 weeks

Hematopoietic:

* Absolute granulocyte count greater than 1,500/mm\^3
* Hemoglobin greater than 8 g/dL
* Platelet count greater than 100,000/mm\^3

Hepatic:

* Bilirubin normal
* SGPT less than 2 times upper limit of normal
* No significant hepatic dysfunction

Renal:

* Creatinine normal OR
* Creatinine clearance at least 60 mL/min

Cardiovascular:

* No significant cardiac dysfunction

Pulmonary:

* No significant pulmonary dysfunction

Other:

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* Able to swallow capsules
* No significant unrelated systemic illness that would preclude study (e.g., serious infections or organ dysfunction)
* No prior hypersensitivity to dacarbazine, temozolomide, or polyethylene glycol

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* At least 1 week since prior colony-stimulating factors (e.g., filgrastim \[G- CSF\], sargramostim \[GM-CSF\], or epoetin alfa)
* At least 4 months since prior myeloablative therapy requiring bone marrow or stem cell transplantation
* No concurrent anticancer immunotherapy

Chemotherapy:

* See Disease Characteristics
* At least 3 weeks since prior chemotherapy (4 weeks for nitrosoureas) and recovered
* Prior temozolomide allowed provided not administered within past 3 months, no severe toxicities experienced during prior course, and not given in combination with other agents designed to inactivate alanine-glyoxylate aminotransferase
* No other concurrent investigational or standard anticancer chemotherapy

Endocrine therapy:

* Concurrent corticosteroids for control of brain tumor-associated edema allowed provided on stable or decreasing dose for at least 1 week prior to study

Radiotherapy:

* See Disease Characteristics
* At least 4 weeks since prior limited-field radiotherapy
* At least 4 months since prior craniospinal irradiation, total body irradiation, or radiotherapy to more than half of the pelvis
* Recovered from prior radiotherapy
* No concurrent anticancer radiotherapy

Surgery:

* See Disease Characteristics

Other:

* At least 4 weeks since other prior investigational therapy and recovered
* No other concurrent anticancer investigational agents