atrasentan in treating patients with progressive or recurrent malignant glioma

Conditions: Brain and Central Nervous System Tumors

Summary: rationale: drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. purpose: phase i trial to study the effectiveness of atrasentan in treating patients who have progressive or recurrent malignant glioma.

objectives: * determine the maximum tolerated dose of atrasentan in patients with progressive or recurrent malignant glioma. * describe the pharmacokinetics of this drug in these patients. * assess preliminary evidence of therapeutic activity of this drug in these patients. outline: this is a dose-escalation, multicenter study. patients receive oral atrasentan once daily. courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. cohorts of 2-10 patients receive escalating doses of atrasentan until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which at least 1 patient experiences dose-limiting toxicity. patients are followed every 2 months. projected accrual: approximately 35 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically confirmed malignant glioma * anaplastic astrocytoma * anaplastic oligodendroglioma * glioblastoma multiforme * progressive or recurrent after prior radiotherapy with or without chemotherapy * prior low-grade glioma that has progressed to high-grade after therapy allowed * measurable disease by mri or ct scan patient characteristics: age: * 18 and over performance status: * karnofsky 60-100% life expectancy: * not specified hematopoietic: * absolute neutrophil count at least 1,500/mm\^3 * platelet count at least 100,000/mm\^3 hepatic: * bilirubin no greater than 1.5 mg/dl * transaminases no greater than 4 times upper limit of normal * hepatitis a, b, and c negative renal: * creatinine no greater than 1.7 mg/dl cardiovascular: * no new york heart association class ii, iii, or iv cardiac disease other: * hiv negative * mini mental score at least 15 * no other malignancy within the past 5 years except curatively treated carcinoma in situ or basal cell skin cancer * no serious concurrent infection * no other concurrent medical illness that would preclude study entry * no alcoholism or drug addiction within the past 6 months * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception prior concurrent therapy: biologic therapy: * no concurrent anticancer immunotherapy chemotherapy: * see disease characteristics * at least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered * no more than 1 prior chemotherapy regimen * no prior or concurrent polifeprosan 20 with carmustine implant (gliadel wafer) * no prior atrasentan * no other concurrent anticancer chemotherapy endocrine therapy: * no concurrent anticancer hormonal therapy radiotherapy: * see disease characteristics * at least 3 months since prior radiotherapy and recovered * no concurrent anticancer radiotherapy surgery: * no concurrent anticancer surgery other: * recovered from prior therapy * no more than 1 prior treatment regimen * no other concurrent investigational agents

Keywords: recurrent adult brain tumor adult glioblastoma adult anaplastic astrocytoma adult anaplastic oligodendroglioma adult giant cell glioblastoma adult gliosarcoma