carmustine in treating patients with progressive or recurrent glioblastoma multiforme

Conditions: Brain and Central Nervous System Tumors

Summary: rationale: drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. purpose: phase ii trial to study the effectiveness of carmustine in treating patients who have progressive or recurrent glioblastoma multiforme.

objectives: * determine the maximum tolerated dose of intratumoral carmustine in ethanol (dti-015) in patients with unresectable recurrent glioblastoma multiforme. (phase i of this study closed to accrual as of 01/15/2002.) * determine the qualitative and quantitative toxicity of this regimen in these patients. * assess the activity of this regimen in these patients. * estimate peripheral blood carmustine levels in these patients treated with this regimen. outline: this is a dose-escalation, multicenter study. patients receive carmustine in ethanol (dti-015) intratumorally over 5 minutes during stereotactic biopsy or open craniotomy. cohorts of 3-6 patients receive escalating doses of dti-015 until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 3 of 6 patients experience dose-limiting toxicity. (phase i of this study closed to accrual as of 01/15/2002.) additional patients then receive treatment with dti-015 at the recommended phase ii dose. patients are followed at 4, 8, and 12 weeks and then every 1-3 months until disease progression. projected accrual: a total of 12 patients were accrued for phase i of this study and approximately 14-18 patients will be accrued for phase ii of this study. (phase i of this study closed to accrual as of 01/15/2002.)

Eligibility criteria:
disease characteristics: * histologically proven supratentorial malignant glioblastoma multiforme * clear evidence of disease progression by mri * unresectable tumor that has spherical, spheroid, or ovoid shape (not multicentric or multilobulated) * central necrosis and/or central cystic areas allowed in the presence of enhancing rim thickness greater than 5 mm * no brainstem (pons or medulla) or midbrain (mesencephalon) involvement * no involvement of primary sensorimotor cortex in the dominant hemisphere or within 1.5 cm of the optic chiasm, either optic nerve, or any other cranial nerve * no tumor extension into the ventricular system * tumor volume no greater than 33.4 cm3 * at least one prior radiotherapy patient characteristics: age: * 18 to 75 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 * no evidence of bleeding diathesis hepatic: * bilirubin no greater than 2.0 mg/dl * sgot/sgpt no greater than 2.5 times normal renal: * creatinine no greater than 2.0 mg/dl or * creatinine clearance at least 40 ml/min * bun no greater than 30 mg/dl other: * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no active uncontrolled infection * afebrile unless fever due to presence of tumor * no other concurrent serious medical or psychiatric illness that would preclude study prior concurrent therapy: biologic therapy: * not specified chemotherapy: * at least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin including gliadel wafer therapy) and recovered endocrine therapy: * not specified radiotherapy: * see disease characteristics * at least 4 weeks since prior radiotherapy and recovered * no prior intracranial brachytherapy surgery: * recovered from any prior surgery other: * no prior anticoagulants * no other concurrent investigational agents

Keywords: recurrent adult brain tumor adult glioblastoma adult giant cell glioblastoma adult gliosarcoma