Phase I Study Of Suberoylanilide Hydroxamic Acid (SAHA) (NSC 701852) in Combination With Paclitaxel /Carboplatin for Advanced and Refractory Solid Malignancies
I. Determine the recommended phase II dose of vorinostat (SAHA) when administered with
paclitaxel and carboplatin in patients with advanced or refractory solid tumors.
I. Determine the dose-limiting toxicity (DLT) and other toxic effects of this regimen in
II. Assess, preliminarily, evidence of antitumor activity of this regimen in these patients.
III. Determine the pharmacokinetic parameters of this regimen in these patients.
IV. Determine the in vivo effects of this regimen in these patients.
OUTLINE: This is a multicenter, dose-escalation study of vorinostat (SAHA).
Patients receive oral SAHA once or twice daily on days 1-14* and paclitaxel IV over 3 hours
followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up
to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who
have stable disease after the completion of 6 courses may receive single-agent SAHA at the
discretion of the treating physician.
NOTE: *During the first treatment course only, patients receive SAHA on days -4 to
10.Cohorts of 3-6 patients receive escalating doses of SAHA 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 DLT. An additional 6-12 patients are treated at the MTD.
After completion of study treatment, patients are followed at 1 month.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of vorinostat defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience DLT
University of Pittsburgh
United States: Food and Drug Administration
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