RATIONALE: Suberoylanilide hydroxamic acid may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. PURPOSE: Phase I trial to study the effectiveness of suberoylanilide hydroxamic acid in treating patients who have advanced cancer.
OBJECTIVES: * Determine the maximum tolerated dose of suberoylanilide hydroxamic acid in patients with advanced solid tumors or hematologic malignancies. * Evaluate the pharmacokinetic profile of this drug in these patients. * Determine the effects of this drug on absorption in the fasting and non-fasting states in these patients. * Determine any anti-tumor effects of this drug in these patients. * Correlate clinical outcomes with histone acetylation in circulating mononuclear cells and tumor biopsy samples in patients treated with this drug. OUTLINE: This is a dose-escalation study. Patients are stratified according to disease (solid tumor vs multiple myeloma or lymphoma vs leukemia or myelodysplastic syndromes). The initial 15-20 patients (in the solid tumor or multiple myeloma or lymphoma stratum) receive suberoylanilide hydroxamic acid (SAHA) IV over 2 hours on day 1 of week 0 and then orally once or twice daily beginning on day 1 of week 1. All remaining patients receive oral SAHA once or twice daily beginning on day 1 of week 1. Courses repeat every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. In each stratum, 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 at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients are followed monthly for resolution of adverse events. PROJECTED ACCRUAL: A maximum of 114 patients (42 with solid tumors, 36 with lymphoma or multiple myeloma, and 36 with leukemia or myelodysplastic syndromes) will be accrued for this study within 1 year.
Study Type
INTERVENTIONAL
Purpose
TREATMENT
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
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