Alanosine in Treating Patients With Progressive or Recurrent Malignant Gliomas

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as alanosine, use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: This phase I trial is studying the side effects and best dose of alanosine in treating patients with high-grade progressive or recurrent malignant gliomas.

Detailed Description
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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 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.

Official Title
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A Phase I/II, Open-Label, Non-Randomized, Multicenter, Single Agent Study Of Intravenous SDX-102 For The Treatment Of Patients With MTAP-Deficient High Grade Recurrent Malignant Gliomas

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: L-alanosine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: L-alanosine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult anaplastic oligodendroglioma, adult anaplastic astrocytoma, adult glioblastoma, recurrent adult brain tumor, adult giant cell glioblastoma, adult gliosarcoma