Clinical Trial Finder

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

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.