col-3 in treating patients with progressive or recurrent brain tumors

Conditions: Brain and Central Nervous System Tumors

Summary: rationale: col-3 may stop the growth of brain tumors by stopping blood flow to the tumor. purpose: phase i/ii trial to study the effectiveness of col-3 in treating patients who have progressive or recurrent brain tumors following radiation therapy or chemotherapy.

objectives: * determine the maximum tolerated dose, dose limiting toxicity, and safety profile of oral col-3 alone or when combined with anticonvulsants known to be metabolized by cyp450 in patients with progressive or recurrent high grade anaplastic astrocytoma, anaplastic oligodendroglioma, or glioblastoma multiforme. * define the pharmacokinetics and pharmacodynamics of col-3 on this schedule and determine the effects of hepatic enzyme inducing drugs, such as anticonvulsants, on the pharmacokinetics. * determine the response rate, disease free survival, and survival in patients treated with this regimen. outline: this is a dose-escalation, multicenter study of col-3. patients are stratified by anticonvulsant (anticonvulsants that cause induction of cyp450 vs anticonvulsants that cause modest or no induction of cyp450 or no anticonvulsant). * phase i: patients receive oral col-3 daily. treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of col-3 until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicity. * phase ii: patients receive oral col-3 daily at the mtd from the phase i portion of this study. patients are followed every 2 months until death. projected accrual: a total of 15-18 patients will be accrued for phase i of the study and a total of 35 patients will be accrued for phase ii of the study at a rate of 3 patients per month.

Eligibility criteria:
disease characteristics: * histologically proven high grade glioma that is progressive or recurrent following radiotherapy or chemotherapy * anaplastic astrocytoma * anaplastic oligodendroglioma * glioblastoma multiforme * prior low grade glioma that has progressed to high grade glioma following radiotherapy and/or chemotherapy 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 normal * sgot or sgpt no greater than 2.5 times upper limit of normal renal: * creatinine no greater than 1.5 mg/dl or * creatinine clearance greater than 60 ml/min cardiovascular: * no myocardial infarction, stroke, or congestive heart failure within the past 3 months other: * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception during and for 1 month after study * no serious active infection or medical illness that would preclude compliance * hiv negative * no history of gastrointestinal disorders that would interfere with absorption of study drug * no other malignancy within the past 5 years except curatively treated carcinoma in situ of the cervix or breast, or basal cell or squamous cell skin cancer * no hypersensitivity to tetracyclines or its derivatives prior concurrent therapy: biologic therapy: * no concurrent filgrastim (g-csf) chemotherapy: * at least 4 weeks since prior chemotherapy (6 weeks since prior nitrosoureas) and recovered * no more than 2 prior chemotherapy regimens endocrine therapy: * not specified radiotherapy: * no prior large field radiotherapy (greater than 20% of total bone marrow) * at least 3 months since other prior radiotherapy and recovered surgery: * no prior major upper gastrointestinal surgery * at least 14 days since other prior major surgery other: * no other concurrent investigational agents * no prolonged sun exposure

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