Trial Information

Phase I/II Study of Topotecan (SKF 104864) With Recombinant GM-CSF (Sargramostim) Used as a Priming Agent in Advanced Malignancies

OBJECTIVES: I. Identify a priming schedule of sargramostim (GM-CSF) that reduces the
percentage of progenitor cells in cycle at the time of chemotherapy administration in
patients with advanced malignancies. II. Determine the maximum tolerated dose and toxic
effects of topotecan when administered with sargramostim in these patients. III. Conduct a
preliminary assessment of the activity of this topotecan regimen in these patients.

OUTLINE: This is a dose escalation study of topotecan. Patients receive priming with
sargramostim (GM-CSF) on days -4 through -2. On day 0, topotecan IV is administered over 30
minutes. Cohorts of 6 patients receive escalating doses of topotecan. The maximum tolerated
dose (MTD) is defined as the dose preceding that at which 2 of 6 patients experience
dose-limiting toxicity (DLT). Sargramostim resumes on day 1 following topotecan, and
continues for 5 days or until sufficient hematologic recovery. The next course of topotecan
is given 48 hours later. Treatment repeats every 6 weeks for 4 courses. Patients are
followed every 3 months for the first year, then every 6 months thereafter.

PROJECTED ACCRUAL: 15-25 patients will be accrued for the duration of 18 months.