This phase I trial studies the side effects and best dose of lonafarnib when given together with temozolomide and to see how well they work in treating patients with glioblastoma multiforme that is has come back or did not respond to previous treatment with temozolomide. Lonafarnib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving lonafarnib together with temozolomide may kill more tumor cells.
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose Sarasar (SCH66336, lonafarnib) when combined with Temodar (temozolomide) in an alternating week schedule. II. To describe the toxicities of the Sarasar and Temodar combination treatment using this dosing schedule. III. To evaluate response as measured by 6-month progression-free survival and objective tumor response. OUTLINE: This is a dose-escalation study of lonafarnib. Patients receive temozolomide orally (PO) once daily (QD) on days 1-7 and 15-21 and lonafarnib PO twice daily (BID) on days 8-14 and 22-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Enrollment
34
Given PO
Given PO
M D Anderson Cancer Center
Houston, Texas, United States
Maximum tolerated dose (MTD) of lonafarnib when given with temozolomide, defined as the dose at which fewer than one-third of patients experience dose-limiting toxicity (DLT)
Time frame: 28 days
Tolerability of regimen in patients with disease progression or recurrence during or after recent completion of treatment with temozolomide
Time frame: Up to 11 years
Progression free survival (PFS)
In the historical dataset, the proportion of patients remaining alive and free from progression at 6 months was 15% (95% confidence interval for ranged from 10% to 19%). We will set p0 to 15% and we will set p1 to 30% (looking for a doubling of the 6-month PFS rate). Based on these design parameters, a two-stage design would require that at least 4 of the initial 19 patients are without progression at 6 months.
Time frame: 6 months
Objective response
Time frame: Up to 11 years
Overall survival
Time frame: Up to 11 years
Treatment-related toxicities
Treatment-related toxicity data will be collected and described.
Time frame: Up to 11 years
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