cc-5013 in treating patients with recurrent glioma

Conditions: Brain and Central Nervous System Tumors

Summary: rationale: cc-5013 may stop the growth of gliomas by stopping blood flow to the tumor. purpose: phase i trial to study the effectiveness of cc-5013 in treating patients who have recurrent glioma.

objectives: * determine the maximum tolerated dose of cc-5013 in patients with recurrent high-grade gliomas. * determine the toxic effects of this drug in these patients. * determine the pharmacokinetics of this drug in these patients. * determine the antiangiogenic activity of this drug in these patients. outline: this is a dose-escalation study. patients are stratified according to concurrent enzyme-inducing antiepileptic drugs (yes vs no). patients receive oral cc-5013 weekly for 3 weeks. treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of cc-5013 until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. patients are followed at 2 weeks. projected accrual: a maximum of 80 patients (40 per stratum) will be accrued for this study within 20 months.

Eligibility criteria:
disease characteristics: * one of the following: * histologically confirmed high-grade glioma * glioblastoma multiforme * gliosarcoma * anaplastic astrocytoma * anaplastic oligodendroglioma * anaplastic mixed oligoastrocytoma * malignant glioma/astrocytoma, not otherwise specified * meningioma * hemangioblastoma * ependymoma * primitive neuroectodermal tumors * hemangiopericytoma * progressive glioma * clinically and radiographically diagnosed brain stem glioma * progressive or recurrent disease as determined by ct scan or mri * biopsy allowed for prior recent (i.e., within the past 12 weeks) resection of recurrent or progressive tumor * must have failed prior radiotherapy patient characteristics: age: * 18 and over performance status: * karnofsky 60-100% life expectancy: * more than 8 weeks hematopoietic: * wbc at least 2,300/mm\^3 * platelet count at least 90,000/mm\^3 * hemoglobin at least 8 g/dl (transfusions allowed) hepatic: * bilirubin less than 3 times upper limit of normal (uln) * sgot less than 3 times uln * no significant active hepatic disease renal: * creatinine less than 2.0 mg/dl or * creatinine clearance at least 60 ml/min * no significant active renal disease cardiovascular: * no significant active cardiac disease other: * no other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix * no significant active psychiatric disease * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception during and for 2 months after study prior concurrent therapy: biologic therapy: * at least 2 weeks since prior interferon * no concurrent immunotherapy chemotherapy: * at least 6 weeks since prior nitrosoureas * at least 4 weeks since prior temozolomide or carboplatin * at least 3 weeks since prior procarbazine * at least 2 weeks since prior vincristine * at least 4 weeks since other prior cytotoxic chemotherapy * no concurrent chemotherapy endocrine therapy: * at least 2 weeks since prior tamoxifen * concurrent steroids allowed for control of the signs and symptoms of increased intracranial pressure if on a stable dose for at least the past 5 days radiotherapy: * see disease characteristics * at least 2 weeks since prior radiotherapy * no concurrent radiotherapy surgery: * see disease characteristics * at least 2 weeks since prior tumor resection other: * at least 2 weeks since other prior noncytotoxic agents * concurrent enzyme-inducing antiepileptic drugs allowed * no concurrent rifampin * no concurrent grapefruit juice * no other concurrent investigational agents

Keywords: recurrent adult brain tumor adult glioblastoma adult anaplastic astrocytoma adult anaplastic oligodendroglioma adult mixed glioma adult ependymoblastoma adult anaplastic ependymoma adult myxopapillary ependymoma adult meningioma adult meningeal hemangiopericytoma adult brain stem glioma adult grade iii meningioma adult giant cell glioblastoma adult gliosarcoma