A Phase I Study of Suberoylanilide Hydroxamic Acid (Vorinostat) in Combination With 5-Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX) in Patients With Colorectal Cancer and Other Solid Tumors
I. Determine the maximum tolerated dose of suberoylanilide hydroxamic acid when administered
with fluorouracil, leucovorin calcium, and oxaliplatin in patients with progressive
metastatic or unresectable colorectal cancer or other solid tumors.
I. Determine the toxicity of this regimen in these patients. II. Determine the
pharmacokinetics of oxaliplatin, fluorouracil, and suberoylanilide hydroxamic acid in these
OUTLINE: This is a dose-escalation study of suberoylanilide hydroxamic acid (SAHA).
Patients receive oral SAHA once or twice daily on days 1-3. Patients also receive
oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 4 followed by
fluorouracil IV over 46 hours on days 4-5. Courses repeat every 14 days in the absence of
disease progression or unacceptable toxicity.
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 dose-limiting toxicity. A total of 10 patients are treated at the MTD.
After completion of study treatment, patients are followed for 4 weeks.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of vorinostat
Graded according to the NCI CTCAE.
Roswell Park Cancer Institute
United States: Food and Drug Administration
|Roswell Park Cancer Institute||Buffalo, New York 14263|