An Open-Labeled, Non-Randomized Phase I Study of Safingol Administered With Cisplatin in Patients With Advanced Solid Tumors
- Determine the maximum tolerated dose (MTD) of safingol when administered with cisplatin
in patients with locally advanced or metastatic solid tumors.
- Determine the toxic effects of this regimen in these patients.
- Determine the clinical pharmacokinetics of this regimen in these patients.
- Determine, preliminarily, the therapeutic activity of this regimen in these patients.
- Determine a safe dose (i.e., near the MTD) for phase II evaluation of this regimen in
- Determine, preliminarily, the role of ceramide and S1P, relative to response and
apoptosis, in patients treated with this regimen.
OUTLINE: This is an open-label, non-randomized, dose-escalation study of safingol.
Patients receive safingol IV over 1 hour and cisplatin IV over 1 hour on day 1. Courses
repeat every 21 days* in the absence of disease progression or unacceptable toxicity.
NOTE: *Patients receive safingol on days 1 and 8 and cisplatin on day 8 for course 1 only;
course 1 is 28 days in duration.
Cohorts of 3-6 patients receive escalating doses of safingol until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 10 additional
patients are treated at that dose level.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Recommended phase II dose as assessed by NCI toxicity scale during 3-4 weeks of treatment
Gary K. Schwartz, MD
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|