A PHASE I CLINICAL AND PHARMACOLOGIC EVALUATION OF PHENYLBUTYRATE IN PATIENTS WITH REFRACTORY SOLID TUMORS: STUDY OF CONTINUOUS EXPOSURE ORAL PHENYLBUTYRATE ON A THREE TIMES DAILY SCHEDULE
I. Determine the maximum tolerated dose of oral phenylbutyrate that can be given three times
daily in patients with refractory solid tumors or lymphoma until disease progression or a
trough plasma concentration of 2-6 micromoles per liter is achieved.
II. Characterize the pharmacokinetics of oral phenylbutyrate absorption, and determine
whether there is time dependence in the systemic clearance rate during multiple dosing.
III. Seek preliminary evidence of therapeutic activity of phenylbutyrate when administered
on this schedule in these patients.
IV. Correlate any observed responses and toxic effects with results of bioassays and tissue
sampling for phenylbutyrate activity.
OUTLINE: This is a dose-seeking study.
All patients receive oral phenylbutyrate three times daily. Groups of 4 or more patients
receive escalating doses of phenylbutyrate until the maximum tolerated dose (MTD) is
determined. Treatment continues until disease progression or unacceptable toxicity
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Michael A. Carducci, MD
Sidney Kimmel Comprehensive Cancer Center
United States: Food and Drug Administration
|Johns Hopkins Oncology Center||Baltimore, Maryland 21287|