A Phase I Study of an Oral Histone Deacetylase Inhibitor, MS-275 (NSC 706995, IND 61,198), in Combination With 13-Cis-Retinoic Acid in Metastatic Progressive Cancer.
I. Determine the dose-limiting toxicity and maximum tolerated dose of MS-275 when
administered with isotretinoin in patients with metastatic, progressive, refractory, or
unresectable solid tumors or lymphomas.
I. Determine, preliminarily, tumor response in patients treated with this regimen.
II. Determine the pharmacokinetic profile of this regimen in these patients.
OUTLINE: This is an open-label, dose-escalation study of MS-275.
Patients receive oral MS-275 once on days 1, 8, and 15 and oral isotretinoin twice daily on
days 1-21. Courses repeat every 28 days in the absence of unacceptable toxicity or disease
progression. Cohorts of 3-6 patients receive escalating doses of MS-275 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 12 patients are treated at
Patients are followed monthly.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Dose limiting toxicities defined as an adverse event which is likely related to the study medication
Graded using the CTCAE version 3.0.
Johns Hopkins University
United States: Food and Drug Administration
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