Phase I Clinical and Pharmacological Study of Suberoylanilide Hydroxamic Acid- SAHA (MSK390) in Patients With Advanced Solid Tumors
OBJECTIVES: I. Determine the maximum tolerated dose of suberoylanilide hydroxamic acid
(SAHA) in patients with refractory malignancies. II. Assess the pharmacokinetic profile of
SAHA in these patients. III. Assess the biologic effects of SAHA on normal tissues and on
tumor cells in these patients.
OUTLINE: This is a dose-escalation study. Patients receive suberoylanilide hydroxamic acid
(SAHA) IV over 2 hours on days 1-3. Treatment repeats every 21 days for 8 courses in the
absence of disease progression or unacceptable toxicity. Accelerated Phase: One patient per
dose level receives escalating doses of SAHA until the maximum tolerated dose (MTD) is
determined. The MTD is defined as the dose preceding that at which a patient experiences
grade 2 or greater toxicity (other than hemoglobin anemia) with the first course or when 2
different patients experience a grade 2 toxicity (other than hemoglobin anemia) during any
course of treatment. Standard Phase: Cohorts of 3-6 patients receive escalating doses of
SAHA until the MTD is determined. The MTD is defined as the dose preceding that at which 2
of 6 patients experience dose-limiting toxicity.
PROJECTED ACCRUAL: Approximately 45 patients will be accrued for this study.
Primary Purpose: Treatment
William K. Kelly, DO
Memorial Sloan-Kettering Cancer Center
United States: Federal Government
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|