Phase I Study Of SCH66336 (Lonafarnib), A Farnesyl Protein Transferase Inhibitor In Combination With Temozolomide In Gliomas
- Determine the maximum tolerated dose and dose-limiting toxicity of lonafarnib when
administered with temozolomide in patients with recurrent primary supratentorial
- Determine the safety and tolerability of this regimen in these patients.
- 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
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
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.
Masking: Open Label, Primary Purpose: Treatment
Dose-limiting toxicity and maximum tolerated dose of lonafarnib determined by CTCAE v3.0
Mario Campone, MD
Centre Regional Rene Gauducheau
United States: Federal Government