Expired Study
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Bethesda, Maryland 20892


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.

Study summary:

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.


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



Primary Contact:

Study Chair
Katherine Warren, MD
National Cancer Institute (NCI)

Backup Contact:


Location Contact:

Bethesda, Maryland 20892
United States

There is no listed contact information for this specific location.

Site Status: N/A

Data Source: ClinicalTrials.gov

Date Processed: October 09, 2019

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