A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Bortezomib in Patients With Advanced Malignancies
I. Determine the maximum tolerated dose of vorinostat (SAHA) and bortezomib in patients with
metastatic or unresectable solid tumors.
I. Determine the pharmacokinetics and antitumor activity of this regimen in these patients.
II. Determine the toxic effects of this regimen in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive oral vorinostat (SAHA) twice daily on days 1-14 in step A. Patients receive
oral vorinostat (SAHA) twice daily on days 1-4 and 8-11 in Step B and bortezomib IV over 3-5
seconds on days 2, 5, 9, and 12 during the first course and on days 1, 4, 8, and 11 during
subsequent courses in both steps A and B. Courses repeat every 21 days in the absence of
disease progression or unacceptable toxicity.
Cohorts of 1-6 patients receive escalating doses of bortezomib 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. Up to 6 additional patients receive
bortezomib at the MTD. Subsequent cohorts of 3-6 patients receive escalating doses of SAHA
until the MTD of that drug is determined.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (MTD) determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0)
University of Wisconsin Hospital and Clinics
United States: Food and Drug Administration
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