Lonafarnib and Temozolomide in Treating Patients With Recurrent Primary Supratentorial Gliomas
RATIONALE: Lonafarnib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving lonafarnib together with temozolomide may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of lonafarnib when given together with temozolomide in treating patients with recurrent primary supratentorial glioma.
Brain and Central Nervous System Tumors
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study Of SCH66336 (Lonafarnib), A Farnesyl Protein Transferase Inhibitor In Combination With Temozolomide In Gliomas|
- Dose-limiting toxicity and maximum tolerated dose of lonafarnib determined by CTCAE v3.0 [ Designated as safety issue: Yes ]
- Response (complete [CR] or partial response [PR]) measured by McDonald's criteria at least 4 weeks after first documented response and every 8 weeks until disease progression or until start of another treatment [ Designated as safety issue: No ]
|Study Start Date:||March 2004|
|Primary Completion Date:||June 2009 (Final data collection date for primary outcome measure)|
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00083096
|Centre de Lutte Contre le Cancer Georges-Francois Leclerc|
|Dijon, France, 21079|
|Centre Regional Rene Gauducheau|
|Nantes-Saint Herblain, France, 44805|
|Centre Hospitalier Universitaire Vaudois|
|Lausanne, Switzerland, CH-1011|
|Study Chair:||Mario Campone, MD||Centre Regional Rene Gauducheau|