OBJECTIVES: Primary * Determine the maximum tolerated dose and dose-limiting toxicity of lonafarnib when administered with temozolomide in patients with recurrent primary supratentorial gliomas. * Determine the safety and tolerability of this regimen in these patients. Secondary * Determine the mechanism of action of lonafarnib in these patients. * Determine the pharmacodynamics and pharmacokinetics of this regimen in these patients. * Determine the activity of this regimen in these patients. * Determine the response to this regimen in patients who have measurable disease. OUTLINE: This is a nonrandomized, multicenter, open-label, dose-escalation study of lonafarnib. Patients receive oral temozolomide once daily on days 2-6 of course 1 and on days 1-5 of all subsequent courses. Patients also receive oral lonafarnib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of lonafarnib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 1 of 6 patients experience dose-limiting toxicity. An additional 3 patients may be treated at the highest dose level achieved. Patients are followed every 8 weeks for 6 months and then every 3 months thereafter. PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study.
DISEASE CHARACTERISTICS: * Histologically confirmed primary supratentorial glioma * Multifocal disease allowed * Recurrent disease after prior surgery and/or radiotherapy * Radiological evidence of increased and/or enhanced target lesion * Amenable to temozolomide therapy PATIENT CHARACTERISTICS: Age * Over 18 Performance status * ECOG 0-2 OR * WHO 0-2 Life expectancy * Not specified Hematopoietic * Neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 10.0 g/dL Hepatic * Alkaline phosphatase \< 2.5 times upper limit of normal (ULN) * Transaminases \< 2.5 times ULN * Bilirubin \< 1.5 times ULN Renal * Creatinine \< 1.7 mg/dL Cardiovascular * Cardiac function clinically normal * Normal 12-lead ECG * QTc ≤ 440 msec on ECG * No ischemic heart disease within the past 6 months Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 3 months after study participation * No unstable systemic disease * No active uncontrolled infection * No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up * No other active or recurrent malignancy within the past 5 years except cone biopsied carcinoma of the cervix or adequately treated basal cell or squamous cell skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy * No concurrent anticancer biologic agents Chemotherapy * At least 4 weeks since prior chemotherapy (6 weeks for temozolomide) * Prior adjuvant chemotherapy allowed * No more than 1 prior chemotherapy regimen for recurrent disease * No other concurrent chemotherapy Endocrine therapy * Concurrent corticosteroids allowed provided treatment remains at a stable or decreasing dose for at least 2 weeks Radiotherapy * See Disease Characteristics * No concurrent radiotherapy Surgery * See Disease Characteristics * At least 3 months since prior surgery for primary brain tumor Other * Concurrent anticonvulsants allowed * No other concurrent anticancer agents * No other concurrent investigational therapy