emd 121974 in treating patients with progressive or recurrent glioma

Conditions: Brain and Central Nervous System Tumors

Summary: rationale: emd 121974 may stop the growth of cancer by stopping blood flow to the tumor. purpose: phase i/ii trial to study the effectiveness of emd 121974 in treating patients who have progressive or recurrent malignant glioma.

objectives: * determine the maximum tolerated dose and dose-limiting toxicity of emd 121974 in patients with progressive or recurrent malignant glioma. * determine the 6-month progression-free survival, clinical response rate, duration of progression-free survival, and overall survival in patients treated with this drug. * determine the effects of this drug on tumor perfusion, measured with magnetic resonance perfusion scan, and markers for angiogenesis in these patients. outline: this is a dose-escalation, multicenter study. patients receive emd 121974 iv over 1 hour twice weekly. courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. cohorts of 6-12 patients receive escalating doses of emd 121974 until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which more than 2 of 6 or 4 of 12 patients experience dose-limiting toxicity. once the mtd is determined, additional patients are treated at the mtd. patients are followed every 2 months. projected accrual: a minimum of 6 patients will be accrued for phase i of this study within 2-3 months. a total of 23-38 patients will be accrued for phase ii of this study within 5-10 months.

Eligibility criteria:
disease characteristics: * histologically confirmed malignant glioma that is progressive or recurrent after radiotherapy and/or chemotherapy * eligible subtypes: * anaplastic astrocytoma * anaplastic oligodendroglioma * glioblastoma multiforme * prior low-grade glioma that has progressed to a high-grade glioma (by biopsy) after radiotherapy and/or chemotherapy allowed * measurable disease by volumetric and magnetic resonance perfusion scan * prior biopsy or resection of recurrent brain tumor allowed 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 normal * transaminases no greater than 2.5 times upper limit of normal renal: * creatinine no greater than 1.5 mg/dl or * creatinine clearance at least 60 ml/min cardiovascular: * no advanced coronary artery disease other: * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no serious concurrent infection or medical illness that would preclude study * no other malignancy within the past 5 years except curatively treated carcinoma in situ or basal cell skin cancer * no history of wound healing disorders * no peptic ulcer disease within the past year * mini mental score of at least 15 * willing and able to undergo mri prior concurrent therapy: biologic therapy: * no concurrent filgrastim (g-csf) chemotherapy: * see disease characteristics * at least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered * no more than 2 prior chemotherapy regimens endocrine therapy: * prior corticosteroids allowed if on stable dose for at least 5 days prior to study * concurrent corticosteroids (e.g., dexamethasone) allowed as clinically needed radiotherapy: * see disease characteristics * at least 3 months since prior radiotherapy and recovered surgery: * see disease characteristics * at least 1 week since prior surgery and recovered * no concurrent elective surgery or dental extractions other: * no other concurrent investigational agents

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