Vorinostat and Carboplatin or Vorinostat and Paclitaxel in Patients With Advanced Solid Tumors: A Pharmacokinetic and Pharmacodynamic Study
PRIMARY OBJECTIVES:
I. To determine whether high dose, short course vorinostat achieves higher peak serum
concentrations than standard dosing.
SECONDARY OBJECTIVES:
I. To determine the toxicity profiles of two different escalated intermittent dosing
schedules of vorinostat combined with carboplatin at an area under curve (AUC) of 5.
II. To describe the response rate in patients with advanced solid tumors treated with these
regimens.
III. To develop pharmacodynamic markers for vorinostat. IV. To determine the toxicity
profiles of escalated intermittent dosing schedule of vorinostat at 1200 mg combined with
paclitaxel at 175 mg/m^2 and to describe the response rate in patients with advanced solid
tumors treated with this regimen.
OUTLINE: Patients are randomized to 1 of 4 treatment arms.
ARM I: Patients receive high-dose vorinostat orally (PO) once daily (QD) on days 1-3 and
low-dose vorinostat PO QD on days 8-10 (course 1). After 5 days, patients receive high-dose
vorinostat PO QD on days 1-3 and carboplatin IV over 30 minutes on day 3 of all subsequent
courses.
ARM II: Patients receive high-dose vorinostat and low-dose vorinostat as in arm I. After 5
days, patients receive lower-dose vorinostat PO QD on days 1-3 and carboplatin IV over 30
minutes on day 3 of all subsequent courses.
ARM III: Patients receive low-dose vorinostat PO QD on days 1-3 and high-dose vorinostat PO
QD on days 8-10 (course 0). After 5 days, patients receive vorinostat and carboplatin as in
arm I.
ARM IV: Patients receive low-dose vorinostat and high-dose vorinostat as in arm III. After 5
days, patients receive vorinostat and carboplatin as in arm II.
ARM V: Patients receive low-dose vorinostat PO QD on days 1-3 and mid-dose vorinostat PO QD
on days 8-10 (course 0). After 5 days, patients receive mid-dose vorinostat PO QD on days
1-3 and paclitaxel IV over 3 hours on day 3.
ARM VI: Patients receive mid-dose vorinostat PO QD on days 1-3 and low-dose vorinostat PO QD
on days 8-10 (course 0). After 5 days, patients receive vorinostat and paclitaxel as in arm
V.
In all arms, courses repeat every 21 days in the absence of disease progression or
unacceptable toxicity.
After completion of study therapy, patients are followed up for 4 weeks.
Interventional
Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Peak concentrations (Cmax) of vorinostat at 400, 1200, and 1600 mg
0 (pre-treatment), 60, 120, 180, 240, 360 and 480 minutes and 24 hours after vorinostat administration on days 3 and 10 of course 0 and on day 3 of course 1
No
Michael Maitland
Principal Investigator
University of Chicago Comprehensive Cancer Center
United States: Food and Drug Administration
NCI-2011-02575
NCT01281176
February 2011
Name | Location |
---|---|
University of Chicago Comprehensive Cancer Center | Chicago, Illinois 60637-1470 |