Clinical Trial Finder

DISEASE CHARACTERISTICS:

• - Histologically confirmed malignant glioma of 1 of the following types: - Anaplastic astrocytoma.

• - Anaplastic oligodendroglioma.

• - Glioblastoma multiforme.

• - Progressive or recurrent disease after prior radiotherapy with or without chemotherapy.

• - Low-grade glioma that progressed after prior radiotherapy with or without chemotherapy and is found to be high-grade glioma after biopsy allowed.

• - No more than 2 prior treatment regimens.

• - Measurable disease by CT scan or MRI.

• - Documented absence of methylthioadenosine phosphorylase (MTAP) on fixed tumor specimens.

PATIENT CHARACTERISTICS: Age.

• - 18 and over.

Performance status.

• - Karnofsky 60-100% Life expectancy.

• - Not specified.

Hematopoietic.

• - Absolute neutrophil count ≥ 1,500/mm^3.

• - Platelet count ≥ 100,000/mm^3.

Hepatic.

• - Bilirubin ≤ 1.5 mg/dL.

• - Transaminases ≤ 4 times upper limit of normal.

Renal.

• - Creatinine ≤ 1.5 mg/dL.

Other.

• - Not pregnant or nursing.

• - Negative pregnancy test.

• - Fertile patients must use effective barrier contraception before, during, and for 4 weeks after study participation.

• - Mini mental state exam score of ≥ 15.

• - No psychological or sociological condition, addictive disorder, or family problem that would preclude study compliance.

• - No other malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast.

• - No concurrent serious infection or medical illness that would preclude study participation.

PRIOR CONCURRENT THERAPY: Biologic therapy.

• - No concurrent prophylactic growth factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF]) Chemotherapy.

• - See Disease Characteristics.

• - At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) Endocrine therapy.

• - Must be maintained on a stable or lower corticosteroid regimen from the time of the baseline scan until the start of study treatment.

• - No concurrent steroids as antiemetics.

Radiotherapy.

• - See Disease Characteristics.

• - At least 3 months since prior radiotherapy.

Surgery.

• - Not specified.

Other.

• - Recovered from prior therapy.

• - More than 10 days since prior anticonvulsant drugs that induce hepatic metabolic enzymes.

- No other concurrent investigational agents

OBJECTIVES:

• - Determine the maximum tolerated dose of alanosine (SDX-102) with or without enzyme-inducible antiepileptic drugs (EIAEDs) in patients with methylthioadenosine phosphorylase (MTAP)-deficient high-grade progressive or recurrent malignant gliomas.

• - Determine the pharmacokinetics of this drug administered concurrently with EIAEDs in these patients.

OUTLINE: This is an open-label, nonrandomized, multicenter, dose-escalation study. Patients are stratified according to concurrent anticonvulsant drug use (drugs that induce hepatic metabolic enzymes vs.#46;drugs that cause modest or no induction of hepatic metabolic enzymes OR no anticonvulsant drug). Patients receive alanosine (SDX-102) IV continuously for 5 days. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of SDX-102 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. After completion of study therapy, patients are followed at 1 week and then every 2 months thereafter. PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study.