Brain and Central Nervous System Tumors
Conditions
Keywords
recurrent adult brain tumor, adult glioblastoma, adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult giant cell glioblastoma, adult gliosarcoma
Brief 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.
Detailed description
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.
Interventions
DRUGincyclinide
Sponsors
National Cancer Institute (NCI)
New Approaches to Brain Tumor Therapy Consortium
Study design
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Countries
United States
Outcome results
None listed