PHASE I STUDY OF THE ORALLY ADMINISTERED BUTYRATE PRODRUG, TRIBUTYRIN, IN PATIENTS WITH SOLID TUMORS
I. Determine the maximum tolerated dose and optimum schedule of tributyrin in patients with
prostate cancer or other solid tumors.
II. Determine the toxic effects of tributyrin in these patients. III. Determine the
pharmacodynamics of tributyrin, including modulation of tumor markers, evaluation of
clinical remission (when possible), assessment of F-reticulocytes and/or F cells, and
evaluation of hemoglobin F before and after treatment, in these patients.
IV. Determine the pharmacokinetics of tributyrin, including maximum plasma concentration,
terminal half-life, area under the concentration time curve, volume of distribution, and
clearance of butyrate, in these patients.
V. Determine the relationship between the pharmacokinetics and toxic or therapeutic
pharmacodynamic effects of butyrate in these patients.
VI. Calculate a tributyrin dose, using results from pharmacokinetic and pharmacodynamic
studies, that achieves sustained butyrate concentrations capable of increasing therapeutic
effects with reduced toxicity.
OUTLINE: This is a dose escalation study.
Patients receive oral tributyrin every 8 hours for 3 weeks. Treatment continues every 4
weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients
who achieve stable disease may receive additional courses at the discretion of the protocol
chairperson. Cohorts of 3-6 patients receive escalating doses of tributyrin until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 6 patients experience dose-limiting toxicity.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
David A. Van Echo, MD
University of Maryland Greenebaum Cancer Center
United States: Food and Drug Administration
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