Phase I and Pharmacokinetic Study of the Farnesyl Transferase Inhibitor, R115777, in Combination With Topotecan
- Determine the dose-limiting toxic effects of R115777 and topotecan in patients with
advanced solid tumors.
- Determine the maximum tolerated dose of this regimen in these patients.
- Determine pharmacokinetic profiles of topotecan alone and in combination with R115777
in these patients.
- Measure the inhibition of ras-farnesylation and topo-1 inhibition in peripheral blood
mononuclear cells in these patients when treated with this regimen.
- Determine activity of this treatment in these patients.
OUTLINE: This is a dose-escalation, multicenter study.
Patients receive oral R115777 twice daily on days 2-21 (in the first course only R115777
begins on day 3) and topotecan IV continuously on days 1-21. Treatment continues every 28
days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of R115777 and topotecan until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 3 or 6
patients experience dose-limiting toxicity.
PROJECTED ACCRUAL: A total of 18-24 patients will be accrued for this study.
Primary Purpose: Treatment
Howard S. Hochster, MD
New York University School of Medicine
United States: Food and Drug Administration
|NYU Cancer Institute at New York University Medical Center||New York, New York 10016|